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In the 3 years between the 2019 and 2022 International Studies Association (ISA) meetings, the profound state of global economic, social, and political upheaval around the world has become unavoidably evident for much, if not most, of the world. Against the backdrop of the COVID-19 pandemic, movements for inclusion and resulting backlashes sprang up across the globe. As scholars of international affairs, the members of the ISA seek to understand and contextualize world events. However, our members and the organization itself are not passive observers of history. These struggles directly influence the personal experiences of many of our members, within and beyond our profession. For these reasons, ISA leadership felt that it was important to mark the 2022 meeting with a Sapphire Series panel to discuss ``International Studies and Struggles for Inclusion.'' The panel brought together ISA members from various sections and backgrounds to offer diverse perspectives on a host of topics: How does the field of international studies understand these developments? How do struggles for inclusion affect our members and community of social scientists? And perhaps most importantly, what should the ISA be doing about them, in terms of both scholarship and organizational decisions?

The interlinkages between peace and sustainability are embedded in several international agreements and declarations and recognized by various research studies. However, the characteristics of their bidirectional relationship remain underexamined. Here we scope the complex and multifaceted relationship between peace and sustainability based on an experts workshop held at Hiroshima University in August 2019. The workshop focused on how peace, as a process or a condition, can help or hinder sustainability and vice versa. Relevant environmental, socio-political, and economic and technological considerations highlighted at the workshop were integrated into a co-designed heuristic guide for investigating the peace-sustainability nexus in the context of global change. The proposed guide aims to assist academic and policy researchers in identifying the specific pathways through which peace and sustainability interact when addressing complex challenges. The reinforcing potential of the two will ultimately depend on the governance and management of global transformations.

Recent studies suggest that the pervasive impacts on global fishery resources caused by stressors such as overfishing and climate change could dramatically increase the likelihood of fishery conflict. However, existing projections do not consider wider economic, social, or political trends when assessing the likelihood of, and influences on, future conflict trajectories. In this paper, we build four future fishery conflict scenarios by considering multiple fishery conflict drivers derived from an expert workshop, a longitudinal database of international fishery conflict, secondary data on conflict driver trends, and regional expert reviews. The scenarios take place between the years 2030 and 2060 in the North-East Atlantic (“scramble for the Atlantic”), the East China Sea (“the remodeled empire”), the coast of West Africa (“oceanic decolonization”), and the Arctic (“polar renaissance”). The scenarios explore the implications of ongoing trends in conflict-prone regions of the world and function as accessible, science-based communication tools that can help foster anticipatory governance capacity in the pursuit of future ocean security.

It is debated whether plate tectonics (horizontal tectonics) or single-lid tectonics (vertical tectonics) dominated the Mesoproterozoic Era. Either rifting of the Nuna/Columbia supercontinent or a localized vertical subsidence and tectonism mechanism within a single tectonic plate is likely recorded in Mesoproterozoic basins. This study summarizes detrital zircon samples from the Mesoproterozoic Belt and Purcell Supergroups and Lemhi subbasin of the western United States and Canada and tests competing rift and intracratonic basin models. Rift models take the observed detrital zircon trends to mean that a non-Laurentian (ca. 1.6–1.5 Ga) detrital zircon component becomes completely absent higher in the section, signifying rifting of the Nuna/Columbia supercontinent at ca. 1.4 Ga. Intracratonic models acknowledge this observed shift in provenance but interpret a long-lived intracratonic setting for the basin following an earlier failed rifting event. The fundamental question is whether the Belt basin represents a failed or successful rift. We used statistical comparison of 72 detrital zircon signatures, reported in the literature and presented in this study, to test the rift model. Samples are not evenly distributed across the basin or its stratigraphy. Non-Laurentian grains are spatially restricted to the northwest part of the basin but are present in all groups, suggesting that the apparent loss of the non-Laurentian population is an artifact of sampling bias. Like stratigraphic boundaries and facies changes, mixing trends are gradual, not sharp or sudden, signifying progressive reworking of Proterozoic zircons and transport from all sides. Archean zircons are localized near the edges of Archean blocks, signifying local down-dropping along cratonic margins. The rift model is therefore rejected in favor of the intracratonic model for the Belt basin on the basis of variable mixing between non-Laurentian and Laurentian sources in both pre–Missoula Group and Missoula Group strata. Far away from plate margins, sediment incrementally filled topographic depressions created by densified and thinned Proterozoic crustal blocks, resulting in vertical down-dropping along preexisting sutures with neighboring Archean blocks. More systematic detrital zircon studies are needed in order to accurately quantify provenance trends in space and time. Continued investigation of the Belt basin may reveal underappreciated or unrecognized vertical tectonic processes that may explain Mesoproterozoic rocks more accurately.

Jacques Lacan defines the Other as the linguistic superstructure of the unconscious. It is the collective network of relations into which the subject is inserted, as the subject is inserted into la...

The bacterial pathogen Staphylococcus aureus is capable of infecting a broad spectrum of host tissues, in part due to flexibility of metabolic programs. S. aureus, like all organisms, requires essential biosynthetic intermediates to synthesize macromolecules. We therefore sought to determine the metabolic pathways contributing to synthesis of essential precursors during invasive S. aureus infection. We focused specifically on staphylococcal infection of bone, one of the most common sites of invasive S. aureus infection and a unique environment characterized by dynamic substrate accessibility, infection-induced hypoxia, and a metabolic profile skewed toward aerobic glycolysis. Using a murine model of osteomyelitis, we examined survival of S. aureus mutants deficient in central metabolic pathways, including glycolysis, gluconeogenesis, the tricarboxylic acid (TCA) cycle, and amino acid synthesis/catabolism. Despite the high glycolytic demand of skeletal cells, we discovered that S. aureus requires glycolysis for survival in bone. Furthermore, the TCA cycle is dispensable for survival during osteomyelitis, and S. aureus instead has a critical need for anaplerosis. Bacterial synthesis of aspartate in particular is absolutely essential for staphylococcal survival in bone, despite the presence of an aspartate transporter, which we identified as GltT and confirmed biochemically. This dependence on endogenous aspartate synthesis derives from the presence of excess glutamate in infected tissue, which inhibits aspartate acquisition by S. aureus Together, these data elucidate the metabolic pathways required for staphylococcal infection within bone and demonstrate that the host nutrient milieu can determine essentiality of bacterial nutrient biosynthesis pathways despite the presence of dedicated transporters.

Aducanumab (Aduhelm) is approved in the United States for the treatment of patients with mild cognitive impairment due to Alzheimer's disease or mild AD dementia. Aducanumab Appropriate Use Recommendations (AURs) have been published and have helped guide best practices for use of aducanumab. As real-world use has occurred and more information has accrued, the AURs require refinement. We update the AURs to better inform appropriate patient selection and improve shared decision-making, safety monitoring, and risk mitigation in treated patients. Based on evolving experience we emphasize the importance of detecting past medical conditions that may predispose to amyloid related imaging abnormalities (ARIA) or may increase the likelihood of ARIA complications including autoimmune or inflammatory conditions, seizures, or disorders associated with extensive white matter pathology. The apolipoprotein E ε4 (APOE4) genotype is strongly associated with ARIA and exhibits a gene dose effect. We recommend that clinicians perform APOE genotyping to better inform patient care decisions, discussions regarding risk, and clinician vigilance concerning ARIA. As most ARIA occurs during the titration period of aducanumab, we suggest performing MRI before the 5th, 7th, 9th, and 12th infusions to improve detection. Uncommonly, ARIA may be recurrent or serious; we suggest additional parameters for treatment discontinuation taking these observations into account. It is important to continue to learn from the real-world use of aducanumab and the AURs will continue to evolve as new information becomes available. This AUR update does not address efficacy, price, or insurance coverage and is provided to assist clinicians to establish best practices for use of aducanumab in the treatment of patients with mild cognitive impairment and mild Alzheimer's dementia.

1. The following study was conducted to evaluate the tolerability of tall oil fatty acid (TOFA) to broiler chickens, at three graded levels as a nutritional additive in complete feed. 2. 256 one-day-old female and male Cobb 500 broiler chickens were assigned to four dietary treatment groups with TOFA at 0 (control), 1.0, 3.0, or 5.0 g/kg within a complete feed for 45 d. 3. Birds were weighed individually on days 0, 16, 31 and 45, and the feed intake, bird weight gain, and feed conversion ratio were calculated for the respective starter, grower and finisher phases and over the whole study. On day 45, blood samples were drawn from each bird for haematology and blood chemistry measurements. Two birds per pen were subjected to gross pathological examination and sampling of several tissues for histopathology, including weighing the liver. 4. The dietary treatments did not affect zootechnical performance variables or mortality over the whole study period. Bird performance was typical for the breed. 5. Haematology, clinical chemistry and histopathology did not reveal any changes associated with dietary TOFA dosing. However, the 5.0 g/kg dose level increased the relative weight of the liver, as a percentage of final body weight, compared to the control group, but there was lack of corresponding histopathology findings. 6. In conclusion, the study indicated that oral administration of TOFA for 45 d in feed was well tolerated by the birds at dietary levels of up to 5.0 g/kg.

In the field of global security studies, inclusion, both in terms of process and outcomes, is certainly having a moment. Like many terms widely adopted by the international security and development communities, the utility of the discourse around inclusion stems in part from its ambiguity. The various contributions to this special issue make good and productive use of this ambiguity and have moved the discussion of inclusive approaches to governance, violence reduction, and peace-building forward. In doing so, however, they have put forth very different conceptualizations and operationalizations of inclusion and exclusion. Thus, my contribution to this symposium identifies these various conceptualizations, discusses the strengths and weaknesses of proposed measures, and concludes with remarks on the normative implications of these analyses.

This article investigates the factors that affect scholarly attention on particular countries in four major international relations (IR) journals: International Studies Quarterly, International Organization, International Security, and World Politics for the period 1970 to the present. The analysis supports three basic conclusions. First, the United States receives the most scholarly attention in leading IR journals by a large margin. Second, a baseline model of scholarly attention, including just population, gross domestic product (GDP), and a dummy for the United States fits the data rather well. Additional factors such as membership in prominent international organizations or involvement in armed conflicts improve model fit, but only marginally, with little evidence of regional or English-language bias. And third, there is only weak evidence that countries with stronger economic and security linkages with the United States receive more attention. However, Israel and Taiwan—two countries with unique security relationships with the United States—receive more scholarly attention than either the baseline or augmented models would predict. Our analysis of bibliometric data from leading IR journals indicates the United States is the three-hundred-thousand-pound blue whale of IR scholarship. However, this emphasis is not particularly outsized when its large population, economy, and its extensive history of participation in interstate wars are taken into account.

Research findings on the relationship between climate and conflict are diverse and contested. Here we assess the current understanding of the relationship between climate and conflict, based on the structured judgments of experts from diverse disciplines. These experts agree that climate has affected organized armed conflict within countries. However, other drivers, such as low socioeconomic development and low capabilities of the state, are judged to be substantially more influential, and the mechanisms of climate–conflict linkages remain a key uncertainty. Intensifying climate change is estimated to increase future risks of conflict. Climate has affected organized armed conflict within countries, and intensifying climate change is estimated to increase future risks of conflict, although other drivers are substantially more influential and the mechanisms of climate–conflict linkages remain uncertain.

Why do governments use deadly force against unarmed protesters? The government’s threat perception may be a function of the mobilization potential of the opposition and/or the size of the ruling elite’s support coalition. Given the high salience of ethnicity in African politics, governments that depend on small ethnic coalitions will see peaceful protests as more threatening, as the opposition may be able to draw on larger numbers of potential dissidents and excluded groups. Alternately, governments with larger, more homogeneous ethnic coalitions will find nonviolent mobilization less threatening and will be less likely to respond with deadly force. Using the Social Conflict Analysis Database, we demonstrate that as the size – and to a lesser extent homogeneity – of the ethnic ruling coalition grows, governments are significantly less likely to use deadly force against nonviolent protesters. This finding is robust to several operationalizations of the size of the government’s support coalition, the inclusion of other measures of ethnic demographics, and estimators that account for the hierarchical nature of the data. Threat perception hinges not only on dissident tactics but on their demands, their mobilization potential, and their capacity to impose costs on the government. This article demonstrates that the size and composition of the government’s ethnic support base matters as well.

Previous research by Goldstone et al. (2010) generated a highly accurate predictive model of state-level political instability. Notably, this model identifies political institutions – and partial democracy with factionalism, specifically – as the most compelling factors explaining when and where instability events are likely to occur. This article reassesses the model’s explanatory power and makes three related points: (1) the model’s predictive power varies substantially over time; (2) its predictive power peaked in the period used for out-of-sample validation (1995–2004) in the original study and (3) the model performs relatively poorly in the more recent period. The authors find that this decline is not simply due to the Arab Uprisings, instability events that occurred in autocracies. Similar issues are found with attempts to predict nonviolent uprisings (Chenoweth and Ulfelder 2017) and armed conflict onset and continuation (Hegre et al. 2013). These results inform two conclusions: (1) the drivers of instability are not constant over time and (2) care must be exercised in interpreting prediction exercises as evidence in favor or dispositive of theoretical mechanisms.

Sustainably managed wild fisheries support food and nutritional security, livelihoods, and cultures (1). Harmful fisheries subsidies—government payments that incentivize overcapacity and lead to overfishing—undermine these benefits yet are increasing globally (2). World Trade Organization (WTO) members have a unique opportunity at their ministerial meeting in November to reach an agreement that eliminates harmful subsidies (3). We—a group of scientists spanning 46 countries and 6 continents—urge the WTO to make this commitment...

In this presentation, we report on a comprehensive and balanced assessment of the relationship between climate and conflict risks and its implications for future directions of research. Research fi...

Scholarship on civil war is overwhelmingly preoccupied with armed activity. Data collection efforts on actors in civil wars tend to reflect this emphasis, with most studies focusing on the identities, attributes, and violent behavior of armed actors. Yet various actors also use nonviolent methods to shape the intensity and variation of violence as well as the duration of peace in the aftermath. Existing datasets on mobilization by non-state actors – such as the Armed Conflict Events and Location (ACLED), Integrated Conflict Early Warning System (ICEWS), and Social Conflict Analysis Database (SCAD) – tend to include data on manifest contentious acts, such as protests, strikes, and demonstrations, and exclude activities like organizing, planning, training, negotiations, communications, and capacity-building that may be critical to the actors’ ultimate success. To provide a more comprehensive and reliable view of the landscape of possible nonviolent behaviors involved in civil wars, we present the Nonviolent Action in Violent Contexts (NVAVC) dataset, which identifies 3,662 nonviolent actions during civil wars in Africa between 1990 and 2012, across 124 conflict-years in 17 countries. In this article, we describe the data collection process, discuss the information contained therein, and offer descriptive statistics and discuss spatial patterns. The framework we develop provides a powerful tool for future researchers to use to categorize various types of nonviolent action, and the data we collect provide important evidence that such efforts are worthwhile.

Background: An oral, fixed-dose sodium phenylbutyrate-ursodoxicoltaurine (PB-TURSO) coformulation was evaluated in a multicenter ALS trial (CENTAUR). Methods: Adults with definite ALS, ≤18 months from symptom onset, (N=137) were randomized 2:1 to PB-TURSO or placebo for 6 months. Completing participants were eligible to receive PB-TURSO in the open-label extension (OLE) (≤30 months). The primary efficacy endpoint in both periods was rate of ALS Functional Rating Scale–Revised (ALSFRS-R) total score decline. All-cause survival was analyzed July 2020 (longest follow-up, 35 months). Safety was assessed in both periods. Results: Over 6-month randomized treatment, mean ALSFRS-R total score decline was slower with PB-TURSO vs placebo (difference, 0.42 points/month; P=0.03). Participants receiving PB-TURSO in the OLE (continued or crossover from placebo) maintained or initiated functional benefit beyond 6 months of therapy. Mean hazard of death was 44% lower (P=0.02) in the original PB-TURSO group. Overall adverse event (AE) incidence was similar, though early (week ≤3) gastrointestinal AEs were more frequent during initial exposure to PB-TURSO (randomized period or OLE). Conclusions: PB-TURSO resulted in superior retention of function in the randomized period. Long-term OLE results support functional benefits of early vs delayed therapy and of sustained treatment. Survival was longer in the original PB-TURSO group after nearly 3 years.

For the second time in the past 3 years, the EU-US CTAD Task Force addressed challenges related to designing clinical trials for agitation in dementia, which is one of the most disruptive aspects of the condition for both patients and caregivers. Six recommendations emerged from the Task Force meeting: 1 – Operationalizing agitation criteria established by the IPA; 2 – Combining clinician- and caregiver-derived outcomes as primary outcome measures; 3 – Using global ratings to define clinically meaningful effects and power studies; 4 – Improving the accuracy of caregiver reports by better training and education of caregivers; 5 – Employing emerging technologies to collect near real-time behavioral data; and 6 – Utilizing innovative trial designs and increasing the use of biomarkers to maximize the productivity of clinical trials for neuropsychiatric symptoms.

This paper presents a detailed sedimentologic investigation of a newly identified, fossiliferous Late Neogene sedimentary succession in the Rukwa Rift Basin, southwestern Tanzania. This synrift deposit is a rare and significant new example of a fossiliferous succession of this age in the Western Branch of East Africa Rift System. The unit, informally termed the lower Lake Beds succession, is late Miocene to Pliocene in age based on cross-cutting relationships, preliminary biostratigraphy, and U-Pb geochronology. An angular unconformity separates the lower Lake Beds from underlying Cretaceous and Oligocene strata. Deposition was controlled by rapid generation of accommodation space and increased sediment supply associated with late Cenozoic tectonic reactivation of the Rukwa Rift and synchronous initiation of the Rungwe Volcanic Centre. The lower Lake Beds, which have thus far only been identified in three localities throughout the Rukwa Rift Basin, are characterized by two discrete lithologic members (herein A and B). The lower Member A is a volcanic-rich succession composed mostly of devitrified volcanic tuffs, and volcaniclastic mudstones and sandstones with minor conglomerates. The upper Member B is a siliciclastic-dominated succession of conglomerates, sandstones, mudstones and minor volcanic tuffs. Detailed facies analysis of the lower Lake Beds reveals various distinctive depositional environments that can be grouped into three categories: 1) alluvial fan; 2) fluvial channel; and 3) flood basin environments, characterized by volcanoclastic-filled lakes and ponds, abandoned channel-fills and pedogenically modified floodplains. Member A represents a shallow lacustrine setting filled by tuffaceous sediments, which grade up into a system of alluvial fans and high-energy, proximal gravel-bed braided rivers. An unconformity marks the contact between the two members. Member B shows an upward transition from a high-energy, gravel-bed braided river system to a sandy braided river system with increasingly abundant floodplain deposits and well-developed paleosols. Vertebrate fossils are sparse in member A, but common in member B, preserved both within pedogenic soil horizons and as isolated elements and microsites within fluvial channel facies associations. Faunal remains include fishes, turtles and crocodylians, along with well-preserved mammal cranial and post-cranial remains. In addition, freshwater gastropod shells are locally present in member A and continental trace fossils, including abundant fossilized termite nests, are present in both members.

Background and objectives U.S. estimates of seasonal influenza (flu) vaccine uptake in 2014–2015 were 62% for 5–12 year olds, dropping to 47% for 13–17 year olds. The Healthy People 2020 goal for these age groups is 80%. It is important to understand factors associated with influenza vaccination, especially for those ages where rates begin to decline. The objective of this study was to identify factors associated with influenza vaccination acceptance in 9–13 year old children. Methods An online U.S. survey of mothers of children aged 9–13 assessed children's influenza vaccine uptake in the previous season, healthcare utilization, sociodemographics, and vaccine attitudes. Multivariable logistic regression identified independent predictors of influenza vaccine status. Results There were 2363 respondents (Mean age = 38 years old). Referent children were 57% female and 66% non-minority race/ethnicity with a mean age of 10.6 years. By maternal report, 59% of children had received an influenza vaccine in the previous season. Predictors of influenza vaccine uptake included a recommendation or strong recommendation from a health care provider, seeing a health care provider in the past year, positive attitudes regarding the influenza vaccine, and being a minority race. Child gender, age, insurance coverage, and whether the child had a regular healthcare provider were not associated with influenza vaccine uptake (p = n.s.). Conclusions This sample reported overall rates of influenza vaccine uptake similar to national surveillance data, but still lower than national goals. Provider recommendations along with health attitudes and seeing a health care provider were associated with vaccine uptake. Promising interventions may include more directive physician messaging for influenza vaccine uptake in youth, encouraging more regular well-child visits during the adolescent years, and promoting influenza vaccination at alternative sites.

The streetlight effect is the tendency for researchers to focus on particular questions, cases and variables for reasons of convenience or data availability rather than broader relevance, policy import, or construct validity. To what extent does the streetlight effect condition the state of knowledge about climate change in Africa? Analysis of Google Scholar search results, both general and within leading climate change-related journals, reveals that two proxies for objective need, population and land mass, are associated with a higher volume of scholarly attention. Countries with greater exposure to the negative effects of climate change and countries with less adaptive capacity do not receive more scholarly attention. Rather, I find evidence that factors like British colonial history, strong civil liberties, and to a lesser extent political stability − factors not directly related to risks from climate change − affect scholarly attention. The streetlight effect is evident in climate change research on Africa.

The current research examines the effects of resource availability, assessed here via individual differences in circadian typology, on the use of claimed self-handicapping. Participants high in trait self-handicapping were more likely to claim stress when told it would negatively affect their score on an upcoming intelligence task (versus when told stress would not affect their score). However, this effect emerged only during on-peak (as opposed to off-peak) times, suggesting that the use of self-handicapping depends upon available resources. Further analyses showed that reported stress was mediated by the participants' evaluative concern. Interestingly, participants high in trait self-handicapping reported increased tiredness during on-peak times but when told stress would not impact their scores, suggesting that they invented an alternative self-handicap to excuse anticipated poor performance in the handicap-absent condition. These findings emphasize not only the resource needs required to engage in strategic self-handicapping, but also illustrate that awareness of evaluative concern is intensified when individuals have their full contingent of resources.

The potential links between climate and conflict are well studied, yet disagreement about the specific mechanisms and their significance for societies persists. Here, we build on assessment of the relationship between climate and organized armed conflict to define crosscutting priorities for future directions of research. They include (1) deepening insight into climate‐conflict linkages and conditions under which they manifest, (2) ambitiously integrating research designs, (3) systematically exploring future risks and response options, responsive to ongoing decision‐making, and (4) evaluating the effectiveness of interventions to manage climate‐conflict links. The implications of this expanding scientific domain unfold in real time., Key Points Disagreement about the relationship between climate and the risk of violent conflict persists, limiting societal management of the risksFuture directions for climate‐conflict research include deepening insight on what the links are, when they matter, and how they manifestCompelling opportunities necessitate integrating research designs, responsive to ongoing decision‐making and potential responses

This chapter introduces the concept of civil action. Beginning with an explanation of its roots in the literature on civility, it moves on to demonstrate how civil action fits logically with analyses of microdynamics and contentious politics. Civil action can be undertaken by a wide variety of social actors, and the chapter charts those actors and the authority claims and capabilities that affect their potential for taking civil action. It then explores three ways in which civil action might matter for conflict dynamics: through its effects on relationships, on levels of local violence, and on the overall conflict. Next, it elaborates on how civil action matters—through process and relationships—and when it should be most likely to work. Finally, the chapter outlines the structure of the book and the case studies it includes.

This paper presents the first detailed, outcrop-based sedimentologic investigation of the Pleistocene–Holocene upper Lake Beds succession in the Rukwa Rift Basin, located in the Western Branch of the East African Rift System, southwestern Tanzania. The goal of this investigation is to examine the sedimentary facies and reconstruct the depositional environments of this important archive of Quaternary climate and environmental change. Eleven diagnostic facies associations comprising 24 facies were identified and provide the basis for recognition of three key deposystems: 1) alluvial-to-fluvial channel system; 2) lake delta system; and 3) profundal lacustrine system. Analysis of paleocurrent indicators and sandstone provenance indicate widely dispersed source regions and drainage patterns that were strongly influenced by major border-fault systems and episodic volcanism. Six stratigraphic sequences (A–F), ranging from ∼ 2 to 17 m thick, were identified based on stratal stacking patterns and the development of sequence-bounding unconformities and lacustrine flooding surfaces. Sedimentation processes, facies architecture, and stratigraphic packaging record a complex interplay between Quaternary climate fluctuations and intense episodic volcanism in the nearby Rungwe Volcanic Province, set against large-scale tectonic controls associated with synchronous development of the East African Rift System. Sequence stratigraphic analysis reveals that the Rukwa Rift Basin episodically shifted between a balanced-fill lake basin and an overfilled lake basin. Deep water, basin-wide lake expansion occurred at different times during the late Quaternary. The final depositional sequence preserved in the basin, a fluvial–underfilled lake basin, initiated ∼ 7.9 ka and has persisted to the present day. High-frequency climate change played the key role in sequence development in the upper Lake Beds. However, voluminous, rift-related volcanism and erosion of abundant labile volcanic materials from the Rungwe Volcanic Province, as well as syntectonic evolution of the rift, led to high sedimentation rates and transformation of flash floods and debris flows in the hinterlands (rift margin) to hyperpycnal flows towards the basin depocenter.

Staphylococcus aureus osteomyelitis is a common and debilitating invasive infection of bone. Treatment of osteomyelitis is confounded by widespread antimicrobial resistance and the propensity of bacteria to trigger pathological changes in bone remodeling that limit antimicrobial penetration to the infectious focus. Adjunctive therapies that limit pathogen-induced bone destruction could therefore limit morbidity and enhance traditional antimicrobial therapies. In this study, we evaluate the efficacy of the U.S. Food and Drug Administration-approved, nonsteroidal anti-inflammatory (NSAID) compound diflunisal in limiting S. aureus cytotoxicity toward skeletal cells and in preventing bone destruction during staphylococcal osteomyelitis. Diflunisal is known to inhibit S. aureus virulence factor production by the accessory gene regulator ( agr ) locus, and we have previously demonstrated that the Agr system plays a substantial role in pathological bone remodeling during staphylococcal osteomyelitis. Consistent with these observations, we find that diflunisal potently inhibits osteoblast cytotoxicity caused by S. aureus secreted toxins independently of effects on bacterial growth. Compared to commonly used NSAIDs, diflunisal is uniquely potent in the inhibition of skeletal cell death in vitro . Moreover, local delivery of diflunisal by means of a drug-eluting, bioresorbable foam significantly limits bone destruction during S. aureus osteomyelitis in vivo . Collectively, these data demonstrate that diflunisal potently inhibits skeletal cell death and bone destruction associated with S. aureus infection and may therefore be a useful adjunctive therapy for osteomyelitis.

To replicate and extend a study by the Agency for Healthcare Research and Quality (AHRQ) and Rutgers on antipsychotic use among youths in Medicaid, the authors analyzed Indiana Medicaid claims from 2004 to 2012, extending the earlier study by focusing on second-generation antipsychotics, including both fee-for-service (FFS) and non-FFS patients, and analyzing cost trends.The authors evaluated the impact of several Indiana Medicaid policy changes on medication utilization and cost among children enrolled for at least one month during 2004-2012 (N=683,716-793,637), using an exhaustive antipsychotic list to search the database.Annual utilization rates for antipsychotics were 2%-3% but were much higher among foster children (10%-15%). Policies implemented in 2007 or later were associated with a significant plateauing of utilization in 2008-2012.Growth of second-generation antipsychotic utilization and costs was similar to trends described in the AHRQ-Rutgers study. Several containment strategies appeared effective in addressing these trends.

Childhood immunization involves a balance between parents’ autonomy in deciding whether to immunize their children and the benefits to public health from mandating vaccines. Ethical concerns about pediatric vaccination span several public health domains, including those of policymakers, clinicians, and other professionals. In light of ongoing developments and debates, we discuss several key ethical issues concerning childhood immunization in the United States and describe how they affect policy development and clinical practice. We focus on ethical considerations pertaining to herd immunity as a community good, vaccine communication, dismissal of vaccine-refusing families from practice, and vaccine mandates. Clinicians and policymakers need to consider the nature and timing of vaccine-related discussions and invoke deliberative approaches to policymaking.

The effects of climate change on the ocean environment – especially ocean warming, acidification, and sea level rise – will impact fish stocks and fishers in important ways. Likely impacts include changes in fish stocks’ productivity and distribution, human migration to and away from coastal areas, stresses on coastal fisheries infrastructure, and challenges to prevailing maritime boundaries. In this paper, we explore these and other related phenomena, in order to assess whether and how the impacts of climate change on fisheries will contribute to the risk of fisheries conflict. We argue that climate change will entail an increase in the conditions that may precipitate fisheries conflict, and thereby create new challenges for existing fisheries management institutions. Several potential changes in fisheries management policy are recommended to avert the growing risk of fisheries-related conflicts.

Civil conflict is the most prevalent form of armed conflict in the world today, but this significant driver of food and income security has been largely missing from studies of fisheries. Fisheries conflict is an example of complex dynamics operating in social-ecological systems. We theorize and document the existence of such a feedback loop between conflict in Uganda and fisheries in Lake Victoria. Civil war in northern Uganda resulted in mass human population displacement, which corresponded in time with increases in fishing effort in Lake Victoria. Subsequent changes in catch of Nile perch, the dominant commercial fishery, sparked armed conflict in the lake itself, at Migingo Island, between Uganda and Kenya. From this case study, we draw seven main conclusions. First, these correlation-based relationships are illustrative but not conclusive and we call for further empirical investigation. Second, the couplings between conflict and fishing subsystems are spatially asymmetric: conflict effects are diffuse in their links to broad changes in the fishery, whereas fishery effects may produce more localized conflict events. Third, and most relevant to conflict scholars, the drivers of fishing effort and catch may originate in different subsystems, but their changes and effects must be analyzed in concert. Fourth, the complex and path-dependent impacts of conflicts on natural resources in general, and fisheries in particular, highlights the urgent need for targeted surveys and more mechanistic understanding. Fifth, the open access nature of fisheries in Lake Victoria may exacerbate instabilities not present in other systems. Sixth, the diffuse and context-specific effects of conflicts on fisheries means models of fisheries management (e.g., stock assessment) should not incorporate conflict as a driver at this time. Finally, countries and their stakeholders should focus on diversification in employment for short term coping mechanisms during conflict as a means of short-circuiting the conflict-fisheries feedback loop.

Is research into the links between climate change and conflict biased, and does this bias undermine our ability to draw conclusions about climate-conflict links? Adams et al. (2018, henceforth AIBD) argue the literature on climate-conflict links suffers from endemic sample selection bias. Because of this, the literature overstates links between climate change and conflict. In this article, we revisit the issue of sampling bias in climate-conflict research using a broader measure of scholarly interest based on bibliometric data from Google Scholar searches of some leading journals in the climate-conflict literature. We find i) weaker evidence of sampling on the dependent variable (armed conflict), but some sampling on types of conflict that fit with posited mechanisms and conflict typologies in the climate-conflict literature, and argue that some oversampling of conflict-prone cases may be a warranted; ii) researchers are sampling on the independent variable, with countries more exposed to climate stress receiving more attention; and iii) even stronger evidence of a streetlight effect, with former British colonies and countries of more general interest to scholars and the international community — as proxied by country-specific studies indexed by the Library of Congress and UNESCO World Heritage Sites — receiving greater attention. Thus, our findings both confirm and challenge existing conclusions in the debate over sampling bias in climate-conflict research. While researchers are sampling on climate change stress, the streetlight effect is stronger than previously suggested. This streetlight effect poses significant challenges for research and policy communities: how confidently can we generalize from well-studied cases? Does the streetlight effect diminish our ability to identify the specific economic, political, and social contexts in which climate-related conflicts occur? And finally, should funding agencies take the accumulating evidence for a streetlight effect into account when making funding decisions and prioritizing particular countries and world regions?

Research findings on the relationship between climate and conflict are diverse and contested. Here we assess the current understanding of the relationship between climate and conflict, based on the structured judgments of experts from diverse disciplines. These experts agree that climate has affected organized armed conflict within countries. However, other drivers, such as low socioeconomic development and low capabilities of the state, are judged to be substantially more influential, and the mechanisms of climate-conflict linkages remain a key uncertainty. Intensifying climate change is estimated to increase future risks of conflict.

BackgroundWe explored whether the effects of nilvadipine on cognition were influenced by baseline Alzheimer’s disease (AD) severity.MethodsExploratory analyses were performed on the modified intention-to-treat (mITT) dataset (n = 497) of a phase III randomized placebo-controlled trial to examine the response to nilvadipine in very mild, mild and moderate AD subjects. The outcome measures included total and subscale scores of the Alzheimer’s Disease Assessment Scale Cognitive 12 (ADAS-Cog 12), the Clinical Dementia Rating Scale sum of boxes (CDR-sb) and the AD composite score (ADCOMS), an outcome measure recently developed to detect treatment responses in subjects with prodromal AD. Cerebrospinal fluid (CSF) biomarkers Aβ38, Aβ40, Aβ42, total tau and P181 tau were measured in a subset of samples (n = 55). Regression analyses were adjusted for potential confounders and effect modifiers in order to examine the interactive effects of nilvadipine and AD severity on cognitive outcomes over 78-weeks.ResultsCompared to their respective placebo-controls, nilvadipine-treated, very mild AD subjects showed less decline, whereas moderate AD subjects showed greater decline on the ADAS-Cog 12. Also in very mild AD, a beneficial effect (as measured by ADCOMS), was detected in the nilvadipine treated group. Therapeutic effects of nilvadipine were also observed for a composite memory trait in very mild AD subjects and a composite language trait in mild AD subjects. CSF Aβ42/Aβ40 ratios were increased in mild AD and decreased in moderate AD patients treated with nilvadipine, compared to their respective controls.ConclusionThese data suggest that very mild AD subjects benefited from nilvadipine and that future clinical trials of nilvadipine in this population are required to confirm these findings.Trial RegistrationNCT02017340 Registered 20 December 2013,https://clinicaltrials.gov/ct2/show/NCT02017340EUDRACT Reference Number 2012-002764-27 Registered 04 February 2013,https://www.clinicaltrialsregister.eu/ctr-search/search?query=2012-002764-27

Why do African regimes repress certain contentious challenges but not others? We argue that in addition to opposition claims and tactics, African regimes are especially likely to view challenges expressing ethnic and/or religious claims as threatening. However, in theorizing the decision to use repression, we relax the assumption that the state is a unitary actor. Leaders with a history of factionalism in their security forces face a delegation problem: orders to repress may not be followed or could even cause intraregime violence and/or defections. For this reason, states with divided security forces are less likely to enact repression. This potential for fracturing the regime will be greatest when the challenge has ethnic or religious claims and targets the state, implying an interactive effect. Using the Social Conflict in Africa Database, we find that regimes with a history of past military factionalism are generally less likely to use repression and are especially less likely to repress contentious challenges making ethnic or religious claims.