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Learnings From an Innovative Model to Expand Access to a New and Underutilized Nonhormonal Contraceptive Diaphragm

ABSTRACTWe document the effort over the last 30 years to respond to the call by women advocates at the International Conference on Population and Development for more woman-initiated single or dual-purpose contraceptive methods by developing the Caya contoured diaphragm, an innovative diaphragm designed to meet the needs of women and their partners and expand options for nonhormonal barrier contraception. We describe the complex and interrelated set of activities undertaken to develop the product using a human-centered design process and how we are working to create a corollary sustainable market. This review includes the evidence generated around improved acceptability among couples in low- and middle-income countries and depicts challenges and practical actions on how to dispel misconceptions about diaphragm use. Importantly, we share programmatic lessons learned on increasing universal access to this new sexual and reproductive health technology. Following our new model for increasing access to new and underutilized methods, Caya is now registered and being marketed in nearly 40 countries worldwide.




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Early Lessons From Working With Local Partners to Expand Private-Sector Health Care Networks in Burundi and Mali

ABSTRACTThe private health care sector is an important source of service delivery in low- and middle-income countries (LMICs). Yet, the private sector remains fragmented, making it difficult for health system actors to support and ensure the availability of quality health care services. In global health programs, social franchising is one model used to engage and organize the private health care sector. Two social franchise networks, ProFam in West Africa and Tunza in East and Central Africa, provide health care through branded networks of facilities. However, these social franchise networks include a limited number of private health care facilities, and in fragile contexts, like Burundi and Mali, they have faced challenges in integrating with national health systems. The MOMENTUM Private Healthcare Delivery (MPHD) project in Burundi and Mali sought to expand the number of health facilities it engaged beyond the existing ProFam and Tunza networks. The expansion aimed to help improve service quality in more private facilities while advancing localization and reducing fragmentation for improved stewardship by health system actors. MPHD achieved this expansion by removing barriers for private health facilities to join inclusive, nonbranded networks and engaging local partners to build and maintain these networks. We share lessons learned regarding the growing role of local organizations as actors within mixed health systems and provide insights on strengthening stewardship of the increasingly heterogeneous private health care delivery sector in LMICs, particularly in fragile settings.




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Maturity Assessment of the Health Information System Using Stages of Continuous Improvement Methodology: Results From Serbia

ABSTRACTIntroduction:Since the health information system (HIS) in public health care services in Serbia was introduced in 2009, it has gradually expanded. However, it is unclear how well the HIS components have developed and the whole system’s stage of maturity.Method:In June–September 2021, a maturity assessment of the Serbian HIS was conducted for the first time using the HIS Stages of Continuous Improvement (SOCI) toolkit. The toolkit measures HIS status across 5 HIS domains: leadership and governance, management and workforce, information and communication technology (ICT), standards and interoperability, and data quality and use. The domains were further divided into 13 components and 39 subcomponents whose maturity stage was assessed on a 5-point Likert scale, indicating the level of development: (1) emerging/ad hoc; (2) repeatable; (3) defined; (4) managed; and (5) optimized. The toolkit was applied in a working group of 32 professionals and experts who were engaged in developing the new national eHealth strategy and action plan.Results:The overall maturity score of the Serbian HIS was 1.6, which indicates a low level. The highest baseline score (2) was given to the standards and interoperability domain, and the lowest (1.1) was given to ICT infrastructure. The remaining 3 domains (leadership and governance, Management and Workforce, and Data Quality and Use) were similarly rated (1.7, 1.7, and 1.6, respectively).Conclusion:A baseline assessment of the maturity level of Serbian HIS indicates that the majority of components are between the emerging/ad hoc stage and repeatable, which represent isolated, ad hoc efforts, with some basic processes in place and existing and accessible policies. This exercise provided an opportunity to address identified weaknesses in the upcoming national eHealth strategy.




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Strengthening Capacity for Tailored Immunization Programs Using Adult Learning Principles: A Case Study from Nigeria

ABSTRACTIntroduction: Nigeria has the highest number of children who have not received any vaccines in Africa. The training-of-trainers (TOT) model used to train program managers (PMs) and health care workers (HCWs) is ineffective for adult learning and limits immunization programs’ success. We incorporated adult learning principles (ALPs) in designing and delivering TOT for immunization PMs and HCWs to use data to engage communities for tailored immunization strategies.Methods: Our study was implemented in 3 local government areas (LGAs) of the Federal Capital Territory, Nigeria. A training curriculum was developed, integrating ALPs and technical and operational content based on best practices in delivering immunization training and the training needs assessment findings. State PMs (n=10), LGA PMs (n=30), and HCWs (n=42) were trained on the human-centered design for tailoring immunization programs (HCD-TIP) approaches using ALPs. We used interviews and surveys with purposively and conveniently sampled PMs and HCWs, respectively, and observations to assess participants’ satisfaction, knowledge and competence, behavior changes, and results. The interviews were analyzed thematically, and surveys were statistically.Results: There was a high level of satisfaction with the training among LGA PMs (100%), state PMs (91%), and HCWs (85%), with significant knowledge and competence improvements post-training (P<.001). The trained participants conducted 2 HCD sessions with 24 undervaccinated communities and co-designed 24 prototype solutions for testing. Results showed increased coverage of the pentavalent vaccine first dose (54%) and third dose (188%) across 12 participating communities. Improved community colaboration, communication skills, and data-driven approaches were the most cited behavior changes in practice.Conclusion: The application of ALPs in training, use of HCD-TIP approaches and tools, and supportive supervision enhanced PMs’ and HCWs’ capacity for tailored interventions. Countries should consider adopting a holistic approach that focuses on using these approaches in immunization programs to strengthen the health system for equitable vaccine coverage.




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Select Minor Cannabinoids from Cannabis sativa Are Cannabimimetic and Antinociceptive in a Mouse Model of Chronic Neuropathic Pain [Special Section: Cannabinoid Signaling in Human Health and Disease]

Chronic pain conditions affect nearly 20% of the population in the United States. Current medical interventions, such as opioid drugs, are effective at relieving pain but are accompanied by many undesirable side effects. This is one reason increased numbers of chronic pain patients have been turning to Cannabis for pain management. Cannabis contains many bioactive chemical compounds; however, current research looking into lesser-studied minor cannabinoids in Cannabis lacks uniformity between experimental groups and/or excludes female mice from investigation. This makes it challenging to draw conclusions between experiments done with different minor cannabinoid compounds between laboratories or parse out potential sex differences that could be present. We chose five minor cannabinoids found in lower quantities within Cannabis: cannabinol (CBN), cannabidivarin (CBDV), cannabigerol (CBG), 8-tetrahydrocannabinol (8-THC), and 9-tetrahydrocannabivarin (THCV). These compounds were then tested for their cannabimimetic and pain-relieving behaviors in a cannabinoid tetrad assay and a chemotherapy-induced peripheral neuropathy (CIPN) pain model in male and female CD-1 mice. We found that the minor cannabinoids we tested differed in the cannabimimetic behaviors evoked, as well as the extent. We found that CBN, CBG, and high-dose 8-THC evoked some tetrad behaviors in both sexes, while THCV and low-dose 8-THC exhibited cannabimimetic tetrad behaviors only in females. Only CBN efficaciously relieved CIPN pain, which contrasts with reports from other researchers. Together these findings provide further clarity to the pharmacology of minor cannabinoids and suggest further investigation into their mechanism and therapeutic potential.

SIGNIFICANCE STATEMENT

Minor cannabinoids are poorly studied ligands present in lower levels in Cannabis than cannabinoids like THC. In this study, we evaluated five minor cannabinoids (CBN, CBDV, CBG, THCV, and 8-THC) for their cannabimimetic and analgesic effects in mice. We found that four of the five minor cannabinoids showed cannabimimetic activity, while one was efficacious in relieving chronic neuropathic pain. This work is important in further evaluating the activity of these drugs, which are seeing wider public use with marijuana legalization.




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Correlation of FAPI PET Uptake with Immunohistochemistry in Explanted Lungs from Patients with Advanced Interstitial Lung Disease

Recent studies have demonstrated promising results of fibroblast activation protein (FAP) inhibitor (FAPI) PET in prognosticating and monitoring interstitial lung diseases (ILDs). As a first step toward successful translation, our primary aim was to validate the FAPI PET uptake through immunohistochemistry in patients with advanced ILD who underwent lung transplantation after a FAPI PET scan. Methods: This is a preliminary analysis of a single-center, open-label, single-arm, prospective exploratory biodistribution study of 68Ga-FAPI-46 PET imaging in patients with ILD (NCT05365802). Patients with ILD confirmed by high-resolution CT and scheduled for lung transplant were included. Tissue samples of explanted lungs were obtained from both the central and peripheral lung parenchyma of each lobe. Additional samples were obtained from areas of the lung corresponding to regions of FAPI PET activity. Immunohistochemical staining was performed with an anti-FAP antibody. Percentages of FAP immunohistochemistry-positive area were measured semiautomatically using QuPath software. SUVs in the areas of pathologic samples were measured on FAPI PET/CT by referencing the gross photomap of the explanted lung. A Spearman correlation coefficient test was used to assess the relationship between FAPI PET uptake and FAP immunohistochemical expression in each specimen. Results: Four patients with advanced ILD who underwent FAPI PET/CT before lung transplantation were included. The types of ILD were idiopathic pulmonary fibrosis (n = 2), rheumatoid arthritis–associated ILD (n = 1), and nonspecific interstitial pneumonia (n = 1). FAPI uptake was visualized mainly in the fibrotic area on CT. Twenty-nine surgical pathology samples from 3 patients were analyzed. FAP staining was predominantly positive in fibroblastic foci. FAPI PET SUVmax and SUVmean showed a positive correlation with the immunohistochemical FAP expression score (SUVmax: r = 0.57, P = 0.001; SUVmean: r = 0.54, P = 0.002). Conclusion: In this analysis conducted in patients who underwent lung transplantation after a FAPI PET scan, FAPI PET uptake was positively correlated with FAP immunohistochemistry. These findings provide a rationale for further investigation of FAPI PET as a potential imaging biomarker for ILD.




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Efficacy and Toxicity of [177Lu]Lu-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: Results from the U.S. Expanded-Access Program and Comparisons with Phase 3 VISION Data

The phase 3 VISION trial demonstrated that [177Lu]Lu-PSMA-617 prolonged progression-free survival and overall survival (OS) in prostate-specific membrane antigen [PSMA]–positive metastatic castration-resistant prostate cancer (mCRPC) patients who progressed on taxane-based chemotherapy and androgen receptor–signaling inhibitors (ARSIs). The U.S. expanded-access program (EAP; NCT04825652) was opened to provide access to [177Lu]Lu-PSMA-617 for eligible patients until regulatory approval was obtained. This study aimed to evaluate the efficacy and safety profile of [177Lu]Lu-PSMA-617 within the EAP and compare the results with those from the VISION trial. Methods: Patients enrolled in the EAP at 4 institutions in the United States with available toxicity and outcome data were included. Outcome measures included OS, a prostate-specific antigen (PSA) response rate (RR) of at least 50%, and incidences of toxicity according to Common Terminology Criteria for Adverse Events version 5.0. Differences in baseline characteristics, outcome data, and toxicity between the EAP and VISION were evaluated using t testing of proportions and survival analyses. Results: In total, 117 patients with mCRPC who received [177Lu]Lu-PSMA-617 within the EAP between May 2021 and March 2022 were eligible and included in this analysis. Patients enrolled in the EAP were more heavily pretreated with ARSI (≥2 ARSI regimens: 70% vs. 46%; P < 0.001) and had worse performance status at baseline (Eastern Cooperative Oncology Group score ≥ 2: 19% vs. 7%; P < 0.001) than VISION patients. EAP and VISION patients had similar levels of grade 3 or higher anemia (18% vs. 13%; P = 0.15), thrombocytopenia (13% vs. 8%; P = 0.13), and neutropenia (3% vs. 3%; P = 0.85) and similar PSA RRs (42% vs. 46%; P = 0.50) and OS (median: 15.1 vs. 15.3 mo; P > 0.05). Conclusion: Patients with PSMA-positive mCRPC who received [177Lu]Lu-PSMA-617 within the EAP were later in their disease trajectory than VISION patients. Patients enrolled in the EAP achieved similar PSA RRs and OS and had a safety profile similar to that of the VISION trial patients.




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Drug-Drug Interactions and Synergy: From Pharmacological Models to Clinical Application [Review Article]

This review explores the concept of synergy in pharmacology, emphasizing its importance in optimizing treatment outcomes through the combination of drugs with different mechanisms of action. Synergy, defined as an effect greater than the expected additive effect elicited by individual agents according to specific predictive models, offers a promising approach to enhance therapeutic efficacy while minimizing adverse events. The historical evolution of synergy research, from ancient civilizations to modern pharmacology, highlights the ongoing quest to understand and harness synergistic interactions. Key concepts, such as concentration-response curves, additive effects, and predictive models, are discussed in detail, emphasizing the need for accurate assessment methods throughout translational drug development. Although various mathematical models exist for synergy analysis, selecting the appropriate model and software tools remains a challenge, necessitating careful consideration of experimental design and data interpretation. Furthermore, this review addresses practical considerations in synergy assessment, including preclinical and clinical approaches, mechanism of action, and statistical analysis. Optimizing synergy requires attention to concentration/dose ratios, target site localization, and timing of drug administration, ensuring that the benefits of combination therapy detected bench-side are translatable into clinical practice. Overall, the review advocates for a systematic approach to synergy assessment, incorporating robust statistical analysis, effective and simplified predictive models, and collaborative efforts across pivotal sectors, such as academic institutions, pharmaceutical companies, and regulatory agencies. By overcoming critical challenges and maximizing therapeutic potential, effective synergy assessment in drug development holds promise for advancing patient care.

Significance Statement

Combining drugs with different mechanisms of action for synergistic interactions optimizes treatment efficacy and safety. Accurate interpretation of synergy requires the identification of the expected additive effect. Despite innovative models to predict the additive effect, consensus in drug-drug interactions research is lacking, hindering the bench-to-bedside development of combination therapies. Collaboration among science, industry, and regulation is crucial for advancing combination therapy development, ensuring rigorous application of predictive models in clinical settings.




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Glatiramer Acetate for the Treatment of Multiple Sclerosis: From First-Generation Therapy to Elucidation of Immunomodulation and Repair [Review Article]

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis. Extensive clinical trials and long-term assessments established the efficacy and the safety of GA. Furthermore, studies of the therapeutic processes induced by GA in animal models and in MS patients indicate that GA affects various levels of the innate and the adaptive immune response, generating deviation from proinflammatory to anti-inflammatory pathways. This includes competition for binding to antigen presenting cells; driving dendritic cells, monocytes, and B-cells toward anti-inflammatory responses; and stimulating T-helper 2 and T-regulatory cells. The immune cells stimulated by GA reach the CNS and secrete in situ anti-inflammatory cytokines alleviating the pathological processes. Furthermore, cumulative findings reveal that in addition to its immunomodulatory effect, GA promotes neuroprotective repair processes such as neurotrophic factors secretion, remyelination, and neurogenesis. This review aims to provide an overview of MS pathology diagnosis and treatment as well as the diverse mechanism of action of GA.

Significance Statement

Understanding the complex MS immune pathogenesis provided multiple targets for therapeutic intervention, resulting in a plethora of agents, with various mechanisms of action, efficacy, and safety profiles. However, promoting repair beyond the body’s limited spontaneous extent is still a major challenge. GA, one of the first approved disease-modifying therapies, induces diverse immunomodulatory effects. Furthermore, GA treatment results in elevated neurotrophic factors secretion, remyelination and neurogenesis, supporting the notion that immunomodulatory treatment can support in situ a growth-promoting and repair environment.




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Artificial Intelligence Efficacy as a Function of Trainee Interpreter Proficiency: Lessons from a Randomized Controlled Trial [RESEARCH]

BACKGROUND AND PURPOSE:

Recently, artificial intelligence tools have been deployed with increasing speed in educational and clinical settings. However, the use of artificial intelligence by trainees across different levels of experience has not been well-studied. This study investigates the impact of artificial intelligence assistance on the diagnostic accuracy for intracranial hemorrhage and large-vessel occlusion by medical students and resident trainees.

MATERIALS AND METHODS:

This prospective study was conducted between March 2023 and October 2023. Medical students and resident trainees were asked to identify intracranial hemorrhage and large-vessel occlusion in 100 noncontrast head CTs and 100 head CTAs, respectively. One group received diagnostic aid simulating artificial intelligence for intracranial hemorrhage only (n = 26); the other, for large-vessel occlusion only (n = 28). Primary outcomes included accuracy, sensitivity, and specificity for intracranial hemorrhage/large-vessel occlusion detection without and with aid. Study interpretation time was a secondary outcome. Individual responses were pooled and analyzed with the t test; differences in continuous variables were assessed with ANOVA.

RESULTS:

Forty-eight participants completed the study, generating 10,779 intracranial hemorrhage or large-vessel occlusion interpretations. With diagnostic aid, medical student accuracy improved 11.0 points (P < .001) and resident trainee accuracy showed no significant change. Intracranial hemorrhage interpretation time increased with diagnostic aid for both groups (P < .001), while large-vessel occlusion interpretation time decreased for medical students (P < .001). Despite worse performance in the detection of the smallest-versus-largest hemorrhages at baseline, medical students were not more likely to accept a true-positive artificial intelligence result for these more difficult tasks. Both groups were considerably less accurate when disagreeing with the artificial intelligence or when supplied with an incorrect artificial intelligence result.

CONCLUSIONS:

This study demonstrated greater improvement in diagnostic accuracy with artificial intelligence for medical students compared with resident trainees. However, medical students were less likely than resident trainees to overrule incorrect artificial intelligence interpretations and were less accurate, even with diagnostic aid, than the artificial intelligence was by itself.




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Deep molecular tracking over the 12-yr development of endometrial cancer from hyperplasia in a single patient [RESEARCH REPORT]

Although the progressive histologic steps leading to endometrial cancer (EndoCA), the most common female reproductive tract malignancy, from endometrial hyperplasia are well-established, the molecular changes accompanying this malignant transformation in a single patient have never been described. We had the unique opportunity to investigate the paired histologic and molecular features associated with the 12-yr development of EndoCA in a postmenopausal female who could not undergo hysterectomy and instead underwent progesterone treatment. Using a specially designed 58-gene next-generation sequencing panel, we analyzed a total of 10 sequential biopsy samples collected over this time frame. A total of eight pathogenic/likely pathogenic mutations in seven genes, APC, ARID1A, CTNNB1, CDKN2A, KRAS, PTEN, and TP53, were identified. A PTEN nonsense mutation p.W111* was present in all samples analyzed except histologically normal endometrium. Apart from this PTEN mutation, the only other recurrent mutation was KRAS G12D, which was present in six biopsy samplings, including histologically normal tissue obtained at the patient's first visit but not detectable in the cancer. The PTEN p.W111* mutant allele fractions were lowest in benign, inactive endometrial glands (0.7%), highest in adenocarcinoma (36.9%), and, notably, were always markedly reduced following progesterone treatment. To our knowledge, this report provides the first molecular characterization of EndoCA development in a single patient. A single PTEN mutation was present throughout the 12 years of cancer development. Importantly, and with potential significance toward medical and nonsurgical management of EndoCA, progesterone treatments were consistently noted to markedly decrease PTEN mutant allele fractions to precancerous levels.




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Analysis of Sleep and Circadian Rhythms from Drosophila Activity-Monitoring Data Using SCAMP

Sleep is a fundamental feature of life for virtually all multicellular animals, but many questions remain about how sleep is regulated and what biological functions it plays. Substantial headway has been made in the study of both circadian rhythms and sleep in the fruit fly Drosophila melanogaster, much of it through studies of individual fly activity using beam break counts from Drosophila activity monitors (DAMs). The number of laboratories worldwide studying sleep in Drosophila has grown from only a few 20 years ago to hundreds today. The utility of these studies is limited by the quality of the metrics that can be extracted from the data. Many software options exist to help analyze DAM data; however, these are often expensive or have significant limitations. Therefore, we describe here a method for analyzing DAM-based data using the sleep and circadian analysis MATLAB program (SCAMP). This user-friendly software has an advantage of combining several analyses of both sleep and circadian rhythms in one package and produces graphical outputs as well as spreadsheets of the outputs for further statistical analysis. The version of SCAMP described here is also the first published software package that can analyze data from multibeam DAM5Ms, enabling determination of positional preference over time.




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Books: The Political Economy of Health Care: Where the NHS Came From and Where it Could Lead




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The Changing Role of a Chair and DA: Follow-Up from the 2023 ADFM Annual Conference Session [Family Medicine Updates]




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Highlights from the Respiratory Failure and Mechanical Ventilation Conference 2024

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.




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Column: Why reporting from South Sudan is so difficult — and critically needed

Simona Foltyn walks down a mountain slope shortly after crossing into South Sudan. Photo by Jason Patinkin

In August, fellow reporter Jason Patinkin and I crossed on foot from northern Uganda into rebel-held South Sudan. Over the course of four days, we walked more than 40 miles through the bush, escorted by rebel soldiers, to shed light on one of the world’s most underreported conflicts.

Reporting on South Sudan’s war, which began in 2013, has always been a challenge due to the risk and logistical hurdles associated with accessing remote areas where fighting takes place. But over the past year, covering the war and its humanitarian fallout has become particularly difficult. Since the beginning of this year, South Sudan’s government has banned at least 20 foreign journalists in an apparent effort to silence reporters who had a track record of critically reporting on the government.

The war has had a devastating impact on South Sudanese communities, but much of it has remained out of the limelight of international media.

This systematic crackdown on the foreign press (South Sudanese journalists have long risked imprisonment and death for doing their work) coincided with two important developments. In November 2016, the United Nations warned that the violence being committed against civilians in the southern region of Equatoria risked spiraling into genocide. Then, in February, the UN declared a man-made famine, warning that 100,000 people were at risk of starving to death as a result of civil war.

Journalists seeking to cover these events were left with two equally unsavory options: self-censorship or a risky trip to rebel-held parts of the country. Only a handful of journalists have attempted the latter since fighting escalated in July last year. For us, this was our second embed with the rebels this year.

Martin Abucha (second from right) rests with his troops in rebel-held South Sudan. Photo by Jason Patinkin

We set off from a town in northern Uganda at five in the morning, bouncing along a bumpy dirt track towards the South Sudan border. Crammed into our four-wheel drive were rebel commander Martin Abucha, a dual American and South Sudanese citizen who we planned to profile for our PBS NewsHour Weekend segment, a couple of guides, and several duffle bags stuffed with our tents, sleeping bags, emergency medical kits and provisions to last us four days.

Just as the sun began to rise above a distant range of hills that we aimed to cross later that day, our car came to a halt in front of a stream. Because of the rainy reason, it carried more water than usual. It was time to disembark and start walking, or “footing,” as South Sudanese tend to call it.

We took off our shoes and waded through the stream’s chilly waters. This was the first of a many rivers we’d have to cross along the way, either on foot or in small flimsy canoes dug out from tree trunks. Each time, we dreaded the idea of falling in with our camera gear.

The first part of our journey in northern Uganda felt very much like a hike through a national park. Passing beautiful landscapes and idyllic farming villages, one could almost forget we were headed into a war zone — but we were about to get a reality check.

We had just crossed into South Sudan when out of nowhere, two dozen armed men popped out of the tall grass and surrounded us at gunpoint.

“Stop! Who are you and where are you going?” a soldier called out in Juba Arabic from his hideout no more than 20 yards away, pointing his AK47 at us. Another one next to him had a rocket-propelled grenade propped on his shoulder, also unequivocally aiming it in our direction.

Instinctively, we threw our hands in the air and exchanged a baffled glance. Had we accidentally bumped into government soldiers? Or perhaps we had come onto the “wrong” rebels? Abucha’s group, called the Sudan People’s Liberation Army In Opposition, is the biggest but not the only armed group in Equatoria, an area rife with rival militia and bandits who exploit the security vacuum left by war.

To our relief, and only after Abucha answered a series of questions, this routine security check quickly gave way to a warm welcome. The platoon would be our escort for the next four days as we trekked to their base and to Loa, Abucha’s hometown.

Keeping up with the rebels was no easy task. Given the country’s pervasive lack of basic infrastructure, South Sudanese grow up walking for dozens of miles just to go about their daily lives. For sedentary Westerners, keeping the target pace of “two meters per second” (around five miles an hour) proved challenging amid 90-degree temperatures, all while filming and plowing our way through dense, itchy elephant grass.

The upside of the cumbersome terrain was that it kept us safe. During our four-day trip, we didn’t cross a single road, instead walking along a dizzying network of narrow bush paths the rebels seemed to know like the backs of their hands. An unwanted encounter with government troops, who tended to stick to roads and move around in vehicles as opposed to on foot, was highly unlikely.

The closest we got to government-controlled area was a visit to Loa, located just two kilometers away from a main road frequently patrolled by government soldiers. We couldn’t stay long, but the hour we spent on the ground offered us a glimpse into what villages must look like in many parts of Equatoria: burned mud huts, looted schools and clinics, fallow fields and – most strikingly – no civilians.

The war has had a devastating impact on South Sudanese communities like the one in Loa, but much of it has remained out of the limelight of international media. Our four-day venture into rebel-held South Sudan offered us a rare opportunity to report ground truths, and we are thankful for that.

The post Column: Why reporting from South Sudan is so difficult — and critically needed appeared first on PBS NewsHour.




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U.S.-backed Syrian forces recapture Raqqa from Islamic State group

Fighters of Syrian Democratic Forces celebrate after Raqqa in Syria was liberated from Islamic State militants on Oct. 17. Photo by Erik De Castro/Reuters

U.S.-backed Syrian Democratic Forces announced Tuesday that they had captured the city of Raqqa from Islamic State militants.

“Everything is finished in Raqqa, our forces have taken full control of Raqqa,” SDF spokesman Talal Sello told AFP. A formal declaration would be announced after operations to clear any remaining sleeper cells and to remove landmines in the city were completed, Sello added.

The move is a major setback for the Islamic State which considered Raqqa the de-facto capital of its self-declared caliphate. It comes on the third anniversary of the global effort to defeat ISIS.

Raqqa was the first provincial capital to fall from government control in March 2013 after it was captured by a rebel army. The army included both Syrian opposition groups and more hard line  parties including al-Nusra and the Islamic State.

A civilian government  that was established in the city divided two months later, and less than a year later ISIS recaptured Raqqa and named the the capital of their caliphate.

About 900 civilians have been killed since the the start of the five-month operation, including 570 people in coalition air raids, according to the Syrian Network for Human Rights. The Britain-based Syrian Observatory for Human Rights put the civilian death toll at 1,130 people. American journalist James Foley was beheaded in the mountains south of the city.

SDF fighters pulled down the Islamic State’s black flag from the city’s National Hospital near the city’s stadium, according to a Reuters report.

Special presidential envoy for the Global Coalition to Defeat ISIS Brett McGurk said in August that the U.S. would attempt to perform a “stabilization” in Raqqa — including demining, removing rubble from major pathways to allow trucks and equipment through, and “basic electricity, sewage, water, the basic essentials to allow populations to come back to their home.”

It is not clear when the 300,000 civilians who have fled Raqqa since April during the operation will be able to return.

The post U.S.-backed Syrian forces recapture Raqqa from Islamic State group appeared first on PBS NewsHour.




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As Rohingya refugees continue to flee from persecution, here’s how you can help

A Rohingya refugee girl poses with a chicken at the Balukhali refugee camp near Cox’s Bazar in Bangladesh. Photo by Jorge Silva/Reuters

More than 500,000 Rohingya Muslims have fled their homes since August to escape systematic violence at the hands of government soldiers in Myanmar. The U.N. has called the actions taken by Myanmar forces against the group “a textbook example of ethnic cleansing.”

A report released by Amnesty International on Wednesday documents widespread rape, killings and burnings of Rohingya across the Rakhine State in Myanmar. The report includes extensive interviews of Rohingya refugees who tell stories of live burnings, sexual violence and mass shootings at the hands of soldiers.

To escape persecution, Rohingya refugees are fleeing in droves to neighboring Bangladesh, a country described by some as a reluctant host for the thousands of refugees behind its borders. Conditions within Bangladesh show refugee camps beyond capacity, as organizations struggle to keep up with humanitarian aid.

Find out more: Rohingya Muslims have been denied citizenship in Myanmar since 1982, though they’ve lived in the area since the 12th century. They are not considered one of the country’s official ethnic groups. As such, their lack of official identity bars them from government services and travel.

Officials from Myanmar, a majority Buddhist state, claim Rohingya are actually immigrants from Bangladesh to justify their exclusion of the group. This most recent burst of violence comes from Myanmar’s crackdown following clashes with the Arakan Rohingya Salvation Army (ARSA). After the government declared ARSA a terrorist organization, the retaliation escalated into hundreds of Rohingya villages.

Where to give: BRAC, a top-ranked NGO based out of Bangladesh, is scaling up humanitarian efforts for clean water, health, sanitation and child care for refugees from Myanmar. You can learn more about their efforts here.

An emergency appeal was made by the Disasters Emergency Committee for immediate crisis relief funds. DEC distributes funds to 13 member aid organizations.
UNHCR, UNICEF and Save the Children have donation pages dedicated to the crisis, as does the International Rescue Committee. CNN’s Public Good page provides a user-friendly resource to find NGOs that match your giving goals.

To give to starvation relief, try Action Against Hunger or the World Food Programme.

Be sure to research organizations receiving your financial contributions, not only to find the best organization aligned with your goals, but also to avoid potential scams. For the latest information on aid organizations and charities, visit GuideStar or Charity Navigator to ensure your donations are going in the right direction.

The post As Rohingya refugees continue to flee from persecution, here’s how you can help appeared first on PBS NewsHour.




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RPG Cast – Episode 610: “No One Should Learn Japanese from Super Robot Wars”

Chris embraces our cyberpunk subscription overlords. Josh kills the innkeeper (accidentally). Meanwhile Robert plunges down the .Hack hole.

The post RPG Cast – Episode 610: “No One Should Learn Japanese from Super Robot Wars” appeared first on RPGamer.



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Nintendo and The Pokemon Company Seeking Injunction and Damages from Pocketpair

Nintendo and The Pokémon Company in September filed a patent infringement lawsuit against Palworld developer Pocketpair. 

At the time Nintendo did not share which patents Palworld infringed on, however, Pocketpair has now revealed what patents Nintendo are claiming were infringed on.

"As announced on September 19, 2024, The Pokémon Company and Nintendo Co Ltd (hereinafter referred to as the Plaintiffs) have filed a patent infringement lawsuit against us," said Pocketpair. "We have received inquiries from various media outlets regarding the status of the lawsuit, and we would like to report the details and current status of this case as follows.

"The Plaintiffs claim that Palworld, released by us on January 19, 2024, infringes upon the following three patents held by the Plaintiffs, and are seeking an injunction against the game and compensation for a portion of the damages incurred between the date of registration of the patents and the date of filing of this lawsuit."

Nintendo and The Pokémon Company are each seeking an injunction and damages of five million yen plus late payment damages.

Pocketpair added, "We will continue to assert our position in this case through future legal proceedings. Please note that we will refrain from responding individually to inquiries regarding this case. If any matters arise that require public notice, we will announce them on our website, etc."

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463022/nintendo-and-the-pokemon-company-seeking-injunction-and-damages-from-pocketpair/




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Sony Discusses What Lessons Can be Learned from the Failure of Concord

Sony president Hiroki Totoki in a Q&A session with investors was asked about the failure of Concord, which was shut down less than two weeks after it released.

"Currently, we are still in the process of learning," said Totoki (via VideoGamesChronicle). "And basically, with regards to new IP, of course, you don’t know the result until you actually try it.

"So for us, for our reflection, we probably need to have a lot of gates, including user testing or internal evaluation, and the timing of such gates. And then we need to bring them forward, and we should have done those gates much earlier than we did.

"Also, we have a siloed organisation, so going beyond the boundaries of those organisations in terms of development, and also sales, I think that could have been much smoother.

"And then going forward, in our own titles and in third-party titles, we do have many different windows. And we want to be able to select the right and optimal window so that we can deploy them on our own platform without cannibalization, so that we can maximize our performance in terms of title launches. That’s all I have."

Sony senior vice president for finance and IR Sadahiko Hayakawa discussed the success of Helldivers 2 and the failure of Concord.

"We launched two live-service games this year," he said. "Helldivers 2 was a huge hit, while Concord ended up being shut down. We gained a lot of experience and learned a lot from both.

"We intend to share the lessons learned from our successes and failures across our studios, including in the areas of title development management as well as the process of continually adding expanded content and scaling the service after its release so as to strengthen our development management system.

"We intend to build on an optimum title portfolio during the current mid-range plan period that combines single-player games – which are our strengths and which have a higher predictability of becoming hits due to our proven IP – with live-service games that pursue upside while taking on a certain amount of risk upon release."

Concord released for the PlayStation 5 and PC on August 23, and it was shut down on September 6.

A life-long and avid gamer, William D'Angelo was first introduced to VGChartz in 2007. After years of supporting the site, he was brought on in 2010 as a junior analyst, working his way up to lead analyst in 2012 and taking over the hardware estimates in 2017. He has expanded his involvement in the gaming community by producing content on his own YouTube channel and Twitch channel. You can contact the author on Twitter @TrunksWD.

Full Article - https://www.vgchartz.com/article/463026/sony-discusses-what-lessons-can-be-learned-from-the-failure-of-concord/




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Only toilets will save you from the monsters in Labyrinth of Wild Abyss

From developers Cannibal Interactive, the creators of Purgatory Dungeoneer, springs forth a new labyrinth game. This one is called Labyrinth of Wild Abyss: LayeRedux and it has labyrinths. Except the labyrinths don't just have single paths to their centres, but tube monsters covered in eyes who'll stalk you slowly and methodically as you meander. Personally, it's not the vibe I'm after when I sit down in the evening and I think, "I would like to play a video game that makes me feel somewhat pleasant". But hey, it might be for you.

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Moida Mansion is the new free game from Return Of The Obra Dinn’s Lucas Pope, and it's out now

You remember Lucas Pope, right? He who casually dropped two of the most influential puzzle games ever then got distracted by yellow cranks for six years, occasionally popping up to drop a demake of Papers Please? Well, Pope has ceased hogging that crank, for now at least, and just released Haloween-y adventure game Moida Mansion. It’s on Itch here, and it’s completely free to play in your browser.

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Elder Scrolls: Legends has been removed from sale and will become unplayable in January 2025

The Elder Scrolls: Legends, the free-to-play card game set in Bethesda's fantasy world, has been removed from sale on Steam. Its servers will shut down for good on January 30th, 2025, after which it will no longer be playable. The closure comes five years after the game was last updated.

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Sega are delisting over 60 'classic' games from Steam, including Crazy Taxi and Streets Of Rage

Sega are delisting several bundles of 'classic' games from digital stores, along with "select individual" games. On Steam specifically, this adds up to over 60 games in total, including several actual classics including the original Streets Of Rage trilogy, Crazy Taxi, and Jet Set Radio.

The games will be removed on December 6th but will remain playable to those who already own them.

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Choose between cyberpunk and magic in Zephon, the new 4X from the Warhammer 40,000 – Gladius devs

Warhammer 40,000: Gladius - Relics Of War developers Proxy Studios have just released Zephon, a new 4X strategy game set in a manky, post-apocalyptic world. It's got hexagonal maps, flesh trees, gangly Evangelion-grade giants, "otherworldly hymns of decay", nuclear bombs, and a player-led "blend of magic and cyberpunk" that extends from the city architecture to the research component. All of which is my cup of giblets. Here's the launch trailer.

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Rogue Point is a door-kicking co-op shooter from Black Mesa studio

The developers who remade Half-Life as Black Mesa are working on a new roguelite co-op shooter. It will feature no physicists celebrating Bring Your Shotgun To Work Day, but instead let up to four players tactically breach oil rigs and airports occupied by corporate-sponsored mercenaries. In Rogue Point the richest CEO on earth has croaked it, causing various megacorps to compete in a violent bum rush for control of that wealth. Which is where your team of renegade shooterists come in. They don't want to win this contest, they just want everyone else to lose.

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Grand Theft Auto: The Definitive Edition trilogy on PC gets a classic lighting update from the mobile version

My strongest and most enduring memory of Grand Theft Auto will always be creasing into complete hysterics watching my mate pile into a crumpled police officer with a wooden baseball bat in GTA 3 after school one time. Young’uns these days just don’t appreciate how revolutionary it was to be able to hit a cop with a thing after he’d already fallen over. Suffice it to say I’ve got good memories of the open world series’ nascent forays into 3D, though never enough to tempt me into revisiting them, especially given the poor reception to Grand Theft Auto: The Trilogy - The Definitive Edition. I can sympathise. I’m annoyed just having to type a semicolon and a dash in the same game name.

If you’re in a similarly non-fussed position (I will never not be annoyed that ‘nonplussed’ doesn’t mean what it sounds like it should mean) I can’t imagine a lighting update that’s been available on the mobile versions for a while is enough to tempt you back. But what is a reporter's job if not pathetically treading water between chunklets of Grand Theft Auto news, upon the publishing of which Graham presses the button to release the nutritious pellets on which we all wholly subsist? I hope he doesn’t read that last sentence. I don’t get my pellet if the syntax becomes too convoluted. Moving swiftly on.

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Only one man can save us from Ed Miliband before he wrecks UK economy



Chancellor Rachel Reeves has torpedoed the UK's economic recovery with her tax-and-spend Budget but Ed Miliband is the one who worries me.




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What the new tax year means for your finances - from income to ISAs



Benefit increases, new investment opportunities, and several tax changes are due to come into effect in April.




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Starlink tests show how to save radio astronomy from satellites

Radio astronomers teamed up with SpaceX to find a promising solution for helping expensive telescopes avoid interference from thousands of Starlink satellites




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What are the weird noises coming from Boeing's Starliner capsule?

NASA is investigating a strange noise coming through the speaker on Boeing’s Starliner capsule, which has been beset with technical issues




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Astronauts may need medical evacuation from one-third of moon missions

Medically evacuating an astronaut from space is difficult and expensive, and a new model predicts that one in three long-duration moon missions may require it




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Signals from exotic new stars could hide in gravitational wave data

A computer simulation suggests that some collisions between exotic, hypothetical stars would make space-time ripple with detectable waves




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A dramatic return from space in Kazakhstan

Andrew McConnell's otherworldly photograph captures a Russian cosmonaut in front of the just-landed Soyuz MS spacecraft in Kazakhstan's remote grasslands




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First breathtaking images from Euclid telescope's map of the universe

The Euclid space telescope's massive “cosmic atlas” promises to shed light on fundamental questions in physics and cosmology




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NASA is developing a Mars helicopter that could land itself from orbit

The largest and most ambitious Martian drone yet could carry kilograms of scientific equipment over great distances and set itself down on the Red Planet unassisted




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We are a long way from pregnancy being safe on Mars

Dangerous radiation reaches Mars at levels we aren't exposed to on Earth, which makes the Red Planet a particularly dangerous place to be during pregnancy




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AI can predict tipping points for systems from forests to power grids

Combining two neural networks has helped researchers predict potentially disastrous collapses in complex systems, such as financial crashes or power blackouts




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AI can reveal what’s on your screen via signals leaking from cables

Electromagnetic radiation leaking from the cable between your computer and monitor can be intercepted and decoded by AI to reveal what you are looking at




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What can governments do about online disinformation from abroad?

A cyberterrorism charge in Pakistan connected to riots in the UK illustrates how authorities are reaching across borders to tackle disinformation, but bringing overseas suspects to justice won't always be possible




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We need transparency from the companies disseminating misinformation

As misinformation about the upcoming US elections rockets across social media, creating chaos, companies need to be honest about where this content is coming from, says Annalee Newitz




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Quantum computers teleport and store energy harvested from empty space

A quantum computing protocol makes it possible to extract energy from seemingly empty space, teleport it to a new location, then store it for later use




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Battery-like device made from water and clay could be used on Mars

A new supercapacitor design that uses only water, clay and graphene could source material on Mars and be more sustainable and accessible than traditional batteries




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Tiny battery made from silk hydrogel can run a mouse pacemaker

A lithium-ion battery made from three droplets of hydrogel is the smallest soft battery of its kind – and it could be used in biocompatible and biodegradable implants




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Vulture Festival to Feature Cristin Milioti and a Brief Escape From This

Treat yourself to a Becky Lynch book signing, games with the Dropout stars, Kevin Smith’s Dogma, and so much more!





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Niels Wittich rubbishes FIA announcement just hours after 'stepping down' from role



Former FIA race director Niels Wittich has rejected the motorsport governing body's version regarding his departure.




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How a Robot Is Grabbing Fuel From a Fukushima Reactor



Thirteen years since a massive earthquake and tsunami struck the Fukushima Dai-ichi nuclear power plant in northern Japan, causing a loss of power, meltdowns and a major release of radioactive material, operator Tokyo Electric Power Co. (TEPCO) finally seems to be close to extracting the first bit of melted fuel from the complex—thanks to a special telescopic robotic device.

Despite Japan’s prowess in industrial robotics, TEPCO had no robots to deploy in the immediate aftermath of the disaster. Since then, however, robots have been used to measure radiation levels, clear building debris, and survey the exterior and interior of the plant overlooking the Pacific Ocean.

It will take decades to decommission Fukushima Dai-ichi, and one of the most dangerous, complex tasks is the removal and storage of about 880 tons of highly radioactive molten fuel in three reactor buildings that were operating when the tsunami hit. TEPCO believes mixtures of uranium, zirconium and other metals accumulated around the bottom of the primary containment vessels (PCVs) of the reactors—but the exact composition of the material is unknown. The material is “fuel debris,” which TEPCO defines as overheated fuel that has melted with fuel rods and in-vessel structures, then cooled and re-solidified. The extraction was supposed to begin in 2021 but ran into development delays and obstacles in the extraction route; the coronavirus pandemic also slowed work.

While TEPCO wants a molten fuel sample to analyze for exact composition, getting just a teaspoon of the stuff has proven so tricky that the job is years behind schedule. That may change soon as crews have deployed the telescoping device to target the 237 tons of fuel debris in Unit 2, which suffered less damage than the other reactor buildings and no hydrogen explosion, making it an easier and safer test bed.

“We plan to retrieve a small amount of fuel debris from Unit 2, analyze it to evaluate its properties and the process of its formation, and then move on to large-scale retrieval,” says Tatsuya Matoba, a spokesperson for TEPCO. “We believe that extracting as much information as possible from the retrieved fuel debris will likely contribute greatly to future decommissioning work.”

How TEPCO Plans to Retrieve a Fuel Sample

Getting to the fuel is easier said than done. Shaped like an inverted light bulb, the damaged PCV is a 33-meter-tall steel structure that houses the reactor pressure vessel where nuclear fission took place. A 2-meter-long isolation valve designed to block the release of radioactive material sits at the bottom of the PCV, and that’s where the robot will go in. The fuel debris itself is partly underwater.

The robot arm is being preceded by a smaller telescopic device. The telescopic device, which is trying to retrieve 3 grams of the fuel debris without further contamination to the outside environment, is similar to the larger robot arm, which is better suited for the retrieval of larger bits of debris.

Mitsubishi Heavy Industries, the International Research Institute for Nuclear Decommissioning and UK-based Veolia Nuclear Solutions developed the robot arm to enter small openings in the PCV, where it can survey the interior and grab the fuel. Mostly made of stainless steel and aluminum, the arm measures 22 meters long, weighs 4.6 tons and can move along 18 degrees of freedom. It’s a boom-style arm, not unlike the robotic arms on the International Space Station, that rests in a sealed enclosure box when not extended.

The arm consists of four main elements: a carriage that pushes the assembly through the openings, arm links that can fold up like a ream of dot matrix printer paper, an arm that has three telescopic stages, and a “wand” (an extendable pipe-shaped component) with cameras and a gripper on its tip. Both the arm and the wand can tilt downward toward the target area.

After the assembly is pushed through the PCV’s isolation valve, it angles downward over a 7.2-meter-long rail heading toward the base of the reactor. It continues through existing openings in the pedestal, a concrete structure supporting the reactor, and the platform, which is a flat surface under the reactor.

Then, the tip is lowered on a cable like the grabber in a claw machine toward the debris field at the bottom of the pedestal. The gripper tool at the end of the component has two delicate pincers (only 5 square millimeters), that can pinch a small pebble of debris. The debris is transferred to a container and, if all goes well, is brought back up through the openings and placed in a glovebox: A sealed, negative-pressure container in the reactor building where initial testing can be performed. It will then be moved to a Japan Atomic Energy Agency facility in nearby Ibaraki Prefecture for detailed analysis.

While the gripper on the telescopic device currently being used was able to reach the debris field and grasp a piece of rubble—it’s unknown if it was actually melted fuel—last month, two of the four cameras on the device stopped working a few days later, and the device was eventually reeled back into the enclosure box. Crews confirmed there were no problems with signal wiring from the control panel in the reactor building, and proceeded to perform oscilloscope testing. TEPCO speculates that radiation passing through camera semiconductor elements caused electrical charge to build up, and that the charge will drain if the cameras are left on in a relatively low-dose environment. It was the latest setback in a very long project.

“Retrieving fuel debris from Fukushima Daiichi Nuclear Power Station is an extremely difficult task, and a very important part of decommissioning,” says Matoba. “With the goal of completing the decommissioning in 30 to 40 years, we believe it is important to proceed strategically and systematically with each step of the work at hand.”

This story was updated on 15 October, 2024 to clarify that TEPCO is using two separate tools (a smaller telescopic device and a larger robot arm) in the process of retrieving fuel debris samples.




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Rockstar finally patches GTA Trilogy with fixes after a little help from Netflix



If you wanted to return to GTA Trilogy, now might be the best time as the game has finally got an update after three years which makes it closer to the much better mobile version