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This exploratory study examines the role of project-based learning (PBL) in an Eigogaku (English linguistics) course for preservice English teachers studying at an English medium college in Japan. Three projects were designed to connect the course modules on phonetics/phonology, morphology, and syntax with language teaching applications. At the start and conclusion of the course, students completed a survey that included an open-ended question about the role of linguistics in language teaching and 29 Likert-scale response items targeting their understanding of linguistic concepts, pedagogical applications of linguistics, their beliefs and values about language teaching and learning, and learner autonomy. Responses to the open-ended question showed an increase in explanations of how linguistics can inform pedagogical practices and increase teacher agency. Responses to the Likert-scale items indicated greater understanding of linguistic concepts, pedagogical practices, and learner autonomy, but minimal change regarding beliefs about language learning and teaching. Implications for these findings and recommendations for future research on linguistics education for language teachers are discussed. [ABSTRACT FROM AUTHOR]

Background: Health is increasingly affected by multiple types of crises. Community engagement is recognised as being a critical element in successful crisis response, and a number of conceptual frameworks and global guideline documents have been produced. However, little is known about the usefulness of such documents and whether they contain sufficient information to guide effective community engagement in crisis response. We undertake a scoping review to examine the usefulness of conceptual literature and official guidelines on community engagement in crisis response using a realist-informed analysis [exploring contexts, mechanisms, and outcomes(CMOs)]. Specifically, we assess the extent to which sufficient detail is provided on specific health crisis contexts, the range of mechanisms (actions) that are developed and employed to engage communities in crisis response and the outcomes achieved. We also consider the extent of analysis of interactions between the mechanisms and contexts which can explain whether successful outcomes are achieved or not. Scope and findings: We retained 30 documents from a total of 10,780 initially identified. Our analysis found that available evidence on context, mechanism and outcomes on community engagement in crisis response, or some of their elements, was promising, but few documents provided details on all three and even fewer were able to show evidence of the interactions between these categories, thus leaving gaps in understanding how to successfully engage communities in crisis response to secure impactful outcomes. There is evidence that involving community members in all the steps of response increases community resilience and helps to build trust. Consistent communication with the communities in time of crisis is the key for effective responses and helps to improve health indicators by avoiding preventable deaths. Conclusions: Our analysis confirms the complexity of successful community engagement and the need for strategies that help to deal with this complexity to achieve good health outcomes. Further primary research is needed to answer questions of how and why specific mechanisms, in particular contexts, can lead to positive outcomes, including what works and what does not work and how to measure these processes. [ABSTRACT FROM AUTHOR]

Background: Infectious disease outbreaks like Ebola and Covid-19 are increasing in frequency. They may harm reproductive, maternal and newborn health (RMNH) directly and indirectly. Sierra Leone experienced a sharp deterioration of RMNH during the 2014–16 Ebola epidemic. One possible explanation is that donor funding may have been diverted away from RMNH to the Ebola response. Methods: We analysed donor-reported data from the Organisation for Economic Cooperation and Development (OECD)'s Creditor Reported System (CRS) data for Sierra Leone before, during and after the 2014–16 Ebola epidemic to understand whether aid flows for Ebola displaced aid for RMNH. We estimated aid for Ebola using key term searches and manual review of CRS records. We estimated aid for RMNH by applying the Muskoka-2 algorithm to the CRS and analysing CRS purpose codes. Results: We find substantial increases in aid to Sierra Leone (from $484 million in 2013 to $1 billion at the height of the epidemic in 2015), most of which was earmarked for the Ebola response. Overall, Ebola aid was additional to RMNH funding. RMNH aid was sustained during the epidemic (at $42 m per year) and peaked immediately after (at $77 m in 2016). There is some evidence of a small displacement of RMNH aid from the UK during the period when its Ebola funding increased. Conclusions: Modest changes to RMNH donor aid patterns are insufficient to explain the severe decline in RMNH indicators recorded during the outbreak. Our findings therefore suggest the need for substantial increases in routine aid to ensure that basic RMNH services and infrastructure are strong before an epidemic occurs, as well as increased aid for RMNH during epidemics like Ebola and Covid-19, if reproductive, maternal and newborn healthcare is to be maintained at pre-epidemic levels. [ABSTRACT FROM AUTHOR]

This study presents an experimental investigation into the cyclic performance of a new tube-in-tube buckling restrained brace (BRB) configuration. In this study, reduced- and large-scale brace geometries are tested to quantify inelastic hysteretic response, understand core confinement parameters, and determine the influence of end connection constraints. A total of 11 reduced-scale brace specimens are cyclically tested, along with three large-scale braces representing two core geometries and two core constraint configurations. Results from the reduced- and large-scale brace testing suggest that the tube-in-tube BRB configurations are capable of achieving the required inelastic capacity for qualification in AISC 341-16 specifications. All scaled specimens survived cumulative inelastic demands that exceeded 240 times the yield displacement (with several surviving more than 400 times the yield displacement). Results indicate that tube-in-tube BRBs are capable of producing stable tension-compression hysteretic behavior during cyclic loading. Measured β values for the large-scale Specimen G2 were lower than 1.06 for all deformation cycles at or below 9.2Δby , while measured β values for the large-scale Specimen G3 were lower than 1.07 for all cycles at or below 3.6Δby. The peak β value for Specimens G2 and G3 was 1.16 and occurred during the 15.3Δby and 7.1Δby cycles, respectively. [ABSTRACT FROM AUTHOR]

Exposed column-base connections are commonly overtopped with concrete to provide an even surface with the surrounding floor slab. To facilitate construction, this concrete is poured, after construction of the floor slab, into a blocked out region of the slab in which the column is placed. The result is a shallowly embedded connection that has significantly higher lateral strength and stiffness with respect to the exposed column-base plate connection without the embedment. This has implications for design and, more importantly, seismic performance assessment. Three large-scale experiments are presented to examine the response of such connections. The connections were subjected to combinations of axial compression and cyclic lateral deformation representative of seismic loading. Significant increases in both strength and stiffness (relative to exposed base plate connections) are noted, arising from the block-out concrete resisting the uplift of the base plate. Stable and ductile hysteretic response (similar to exposed column-base plate connections) is also noted. Failure modes include concrete breakout above the base plate and fracture of the anchors. Results from this study are synthesized with results from previous studies on similar connections to propose a strength model, and to evaluate previously proposed models for stiffness. [ABSTRACT FROM AUTHOR]

Samuraciclib is a selective oral CDK7-inhibitor. A multi-modular, open-label Phase I study to evaluate safety and tolerability of samuraciclib in patients with advanced malignancies was designed (ClinicalTrials.gov: NCT03363893). Here we report results from dose escalation and 2 expansion cohorts: Module 1A dose escalation with paired biopsy cohort in advanced solid tumor patients, Module 1B-1 triple negative breast cancer (TNBC) monotherapy expansion, and Module 2A fulvestrant combination in HR+/HER2− breast cancer patients post-CDK4/6-inhibitor. Core study primary endpoints are safety and tolerability, and secondary endpoints are pharmacokinetics (PK), pharmacodynamic (PD) activity, and anti-tumor activity. Common adverse events are low grade nausea, vomiting, and diarrhea. Maximum tolerated dose is 360 mg once daily. PK demonstrates dose proportionality (120 mg-480 mg), a half-life of approximately 75 hours, and no fulvestrant interaction. In dose escalation, one partial response (PR) is identified with disease control rate of 53% (19/36) and reduction of phosphorylated RNA polymerase II, a substrate of CDK7, in circulating lymphocytes and tumor tissue. In TNBC expansion, one PR (duration 337 days) and clinical benefit rate at 24 weeks (CBR) of 20.0% (4/20) is achieved. In combination with fulvestrant, 3 patients achieve PR with CBR 36.0% (9/25); in patients without detectable TP53-mutation CBR is 47.4% (9/19). In this study, samuraciclib exhibits tolerable safety and PK is supportive of once-daily oral administration. Clinical activity in TNBC and HR+/HER2-breast cancer post-CDK4/6-inhibitor settings warrants further evaluation. Pre-clinical studies have demonstrated the anti-tumor activity of selective inhibitors of CDK7, including samuraciclib. Here the authors report the results from dose escalation and two expansion cohorts in patients with breast cancer of a multi-modular Phase I clinical trial of samuraciclib as anti-cancer treatment. [ABSTRACT FROM AUTHOR]

Edward Banfield was one of the first scholars clearly to describe the condition of peasant isolate social ordering, problematically terming it 'amoral familism'. James Scott offered a more positive framing by referring to the potential of 'escape agriculture' to sustain political autonomy. The present paper returns to these debates about peasant moral economy. Norms concerning production and distribution are not exogenous givens but products of communal organization and social context. Banfield's mistake was to refer to peasant autonomy as 'amoral'. Here, isolate ordering has a positive moral valency, and that public authority in zones of war or disaster recovery should seek to accommodate it. [ABSTRACT FROM AUTHOR]

Objective: Ocean planning provides opportunities for managers to evaluate tradeoffs among environmental, social, economic, cultural, and management considerations in the development of place‐based activities. Early integration of mobile protected species considerations into ocean planning reduces the likelihood of future resource conflict. Transparency and problem solving with potential conflicts in mind during the early planning stages can help to minimize contention and increase efficiency in permitting and may also minimize litigation challenges during project design and implementation. Starting with a large area, such as the Bureau of Ocean Energy Management's (BOEM) initial 12.1‐million‐ha call area in federal waters of the U.S. Gulf of Mexico, provided substantial geographic scope for identifying suitable areas for eventual offshore wind lease sales that also aim to minimize conflict across multiple resources and uses. Methods: To support ocean planning for this large‐scale activity, a generalized scoring system for protected species status and trends that facilitates relative comparison between species was developed. Spatial data for species listed under the U.S. Endangered Species Act or the Marine Mammal Protection Act were assembled. Species layers were scored based on species status and trend. The cumulative vulnerability for 23 species groups whose distributions overlap suitable areas proposed for eventual lease sales, termed wind energy areas (WEAs) by BOEM, was calculated. Result: Integrating this combined protected species data layer into the broader Gulf of Mexico WEA ocean planning process helped to reduce potential protected species conflicts by 70%. Conclusion: This generalized approach is directly applicable to other WEAs under consideration within the United States and is transferable to a variety of ocean spatial planning applications. Impact statementThis collaborative work provides a foundation for early engagement and strategic marine spatial planning for offshore wind energy to reduce potential adverse effects to protected species. It also provides a reference for work conducted to inform this process and a template for other regions as these efforts expand. [ABSTRACT FROM AUTHOR]

Steel special moment frames (SMFs) designed per current codes will likely require major repair or be a total loss after design earthquake (DE) shaking. Functional recovery of SMFs can be improved by designing to stricter drift limits, improving postyield stiffness, or improving repairability. In this study, FEMA P-58/ATC-138 (beta) was used to determine the most effective option for improving functional recovery. Eighteen SMFs were designed with different heights (4, 6, and 8 stories), different risk categories (II and IV), and different connections (with varying postyield stiffness and repairability) and were analyzed under response history analysis (RHA). Results from the RHA were used in the FEMA P-58/ATC-138 (beta) analyses to quantify functional recovery for each design. The building designs showed that 6- and 8-story SMFs designed for Risk Category IV were 1.8 to 2.2 times heavier than Risk Category II designs, and that the direct cost premium for Risk Category IV design (versus Risk Category II) was 4%–14% of the total building costs. Response history analysis showed that SMFs with enhanced postyield stiffness had up to 47% lower residual drifts than SMFs with typical postyield stiffness. FEMA P-58/ATC-138 (beta) analyses showed that SMFs with enhanced postyield stiffness and repairability designed to Risk Category II had functional recovery comparable to Risk Category IV SMFs with typical postyield stiffness and repairability. While some proposals to improve functional recovery focus primarily on stiffness and strength, this study demonstrates the relative value of postyield stiffness and repairability. [ABSTRACT FROM AUTHOR]

HIV pre-exposure prophylaxis (PrEP) effectively reduces new HIV diagnoses. High rates of incident bacterial sexually transmitted infections (STIs) have been observed in patients eligible for and adherent to PrEP. Observational studies generally report low long-term retention in PrEP care. Limited data exist on the rates of bacterial STI diagnosis upon re-engagement with PrEP services. We conducted a retrospective chart review within the HIV prevention program of an urban academic medical center in New York City. Eligible patients started PrEP from 2015 to 2019, then resumed PrEP services after a gap in care of at least 180 days. Demographic, clinical, and laboratory data were used to characterize the patient population and rates of bacterial STI diagnosis at re-engagement. In total, 286 patients were identified, with 316 qualifying re-engagement visits. Twenty-nine percent of patients had continued PrEP during the care gap, and 30% reported discontinuing medication due to a perceived change in risk. A new STI was diagnosed at 19% of re-engagement visits. There was no statistically significant difference in rates of new STI between individuals returning on or off PrEP, nor between those with perceived lower risk and those without. Individuals who fall out of PrEP services and subsequently re-engage remain at high risk of bacterial STI during the gap in care, regardless of whether PrEP medication is continued or the patient perceives themselves to be at lower HIV acquisition risk. Providers should strongly encourage patients discontinuing PrEP to remain engaged in sexual health services. Alternatives to clinic-based PrEP care must still include regular bacterial STI screening. [ABSTRACT FROM AUTHOR]

PURPOSE: The prospective Neoadjuvant Breast Registry Symphony Trial compared the 80-gene molecular subtyping signature with clinical assessment by immunohistochemistry and/or fluorescence in situ hybridization in predicting pathologic complete response (pCR) and 5-year outcomes in patients with early-stage breast cancer. METHODS: Standard-of-care neoadjuvant chemotherapy combined with trastuzumab or trastuzumab plus pertuzumab was given to patients with human epidermal growth factor receptor 2 (HER2)–positive tumors (n = 295). pCR was the primary end point, with secondary end points of distant metastasis-free survival and overall survival at 5 years. RESULTS: Among clinically defined HER2-positive (cHER2) tumors, the 80-gene assay identified 29.5% (87 of 295) as Luminal-Type (cHER2/gLuminal), 14.9% (44 of 295) as Basal-Type (cHER2/gBasal), and 55.6% (164 of 295) as HER2-Type (cHER2/genomically classified as HER2 [gHER2]). Patients with cHER2/gHER2 tumors had a higher pCR rate (61.6%) compared with non-gHER2 tumors (26.7%; P <.001). Dual targeting for cHER2/gHER2 tumors yielded a higher pCR rate (75%) compared with those treated with single HER2-targeted therapy (54%; P =.006). For cHER2/gBasal tumors, the 42.9% pCR rate observed with dual targeting was not different from that with trastuzumab alone (46.4%; P =.830). Among those with cHER2/gBasal tumors, 5-year distant metastasis-free survival (68.6%; 95% CI, 49.1 to 81.9) was significantly worse than in patients with cHER2/gLuminal tumors (88.9%; 95% CI, 78.0 to 94.6) and cHER2/gHER2 tumors (87.4%; 95% CI, 80.2 to 92.2; P =.010), with similar corresponding overall survival differences. CONCLUSION: The 80-gene assay identified meaningful genomic diversity in patients with cHER2 disease. Patients with cHER2/gHER2 tumors, who benefitted most from dual HER2-targeted therapy, accounted for approximately half of the cHER2 cohort. Genomically Luminal tumors had low pCR rates but good 5-year outcomes. cHER2/gBasal tumors derived no benefit from dual therapy and had significantly worse 5-year prognosis; these patients merit special consideration in future trials. Genomic characterization of clinically defined HER2+ tumors identifies patients who benefit from dual HER2 therapy. [ABSTRACT FROM AUTHOR]

Background: The Neoadjuvant Breast Symphony Trial (NBRST) demonstrated the 70-gene risk of distant recurrence signature, MammaPrint, and the 80-gene molecular subtyping signature, BluePrint, precisely determined preoperative pathological complete response (pCR) in breast cancer patients. We report 5-year follow-up results in addition to an exploratory analysis by age and menopausal status. Methods: The observational, prospective NBRST (NCT01479101) included 954 early-stage breast cancer patients aged 18–90 years who received neoadjuvant chemotherapy and had clinical and genomic data available. Chemosensitivity and 5-year distant metastasis-free survival (DMFS) and overall survival (OS) were assessed. In a post hoc subanalysis, results were stratified by age (≤ 50 vs. > 50 years) and menopausal status in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) tumors. Results: MammaPrint and BluePrint further classified 23% of tumors to a different subtype compared with immunohistochemistry, with more precise correspondence to pCR rates. Five-year DMFS and OS were highest in MammaPrint Low Risk, Luminal A-type and HER2-type tumors, and lowest in MammaPrint High Risk, Luminal B-type and Basal-type tumors. There was no significant difference in chemosensitivity between younger and older patients with Low-Risk (2.2% vs. 3.8%; p = 0.64) or High-Risk tumors (14.5% vs. 11.5%; p = 0.42), or within each BluePrint subtype; this was similar when stratifying by menopausal status. The 5-year outcomes were comparable by age or menopausal status for each molecular subtype. Conclusion: Intrinsic preoperative chemosensitivity and long-term outcomes were precisely determined by BluePrint and MammaPrint regardless of patient age, supporting the utility of these assays to inform treatment and surgical decisions in early-stage breast cancer. [ABSTRACT FROM AUTHOR]

Ebola Virus Disease struck Sierra Leone in May 2014. An international response was instrumental in ending the epidemic by December 2015 and has been extensively documented. Less attention has been paid to local responses. Here, we focus on a case in which there was no infection despite high infection in neighbouring areas. This brings into focus the role of customary public authority in implementing successful controls. We pay particular attention to the activities of a chiefdom Ebola Task force committee chaired by the Paramount Chief. Meetings were characterised by protocol and ceremony, but 'face time' served to reinforce, in ritual terms, important messages about quarantine and social distancing. The committee's pronouncements had illocutionary force. Local volunteers translated this ceremonial message into practical action to block imported cases. The analysis of ceremonial competence, we conclude, opens a window into how public authority addresses developmental shocks in Africa. [ABSTRACT FROM AUTHOR]

This article shares findings on COVID-19 in Africa across 2020 to examine concepts and practices of epidemic preparedness and response. Amidst uncertainties about the trajectory of COVID-19, the stages of emergency response emerge in practice as interconnected. We illustrate how complex dynamics manifest as diverse actors interpret and modify approaches according to contexts and experiences. We suggest that the concept of "intersecting precarities" best captures the temporalities at stake; that these precarities include the effects of epidemic control measures; and that people do not just accept but actively negotiate these intersections as they seek to sustain their lives and livelihoods. [ABSTRACT FROM AUTHOR]

Rural‐based insurgencies disrupted the forest margins of Upper West Africa in the 1990s. A subsequent return to peace was accompanied by strong growth in small‐scale trade in foodstuffs and other agrarian produce in high demand in towns. Motor cycle taxis are a feature of this increased rural–urban market integration. It was a mode of transport pioneered by ex‐combatants. Where rural women were once attacked by rural young men without job prospects press ganged into fighting for the rebels, bike taxi riders now carry them to rural periodic markets, many of which are new since the end of conflict. The study provides an analytical account of these developments, drawing on discussions with villagers in three heavily war‐affected localities of Sierra Leone. The evidence indicates that communities divided by conflict have quietly built new cooperative links conducive to peace based on local agricultural production and petty trade. [ABSTRACT FROM AUTHOR]

Multiplex polymerase chain reaction testing for gastrointestinal pathogens was performed on a longitudinal cohort of 110 men who have sex with men taking human immunodeficiency virus preexposure prophylaxis. At least 1 pathogen was detected among 50 (45%) participants, with some participants testing positive for the same pathogen on multiple consecutive visits over a period of months. [ABSTRACT FROM AUTHOR]

Background: The Bridging the Age Gap in Breast Cancer research programme sought to improve treatment decision-making for older women with breast cancer by developing and testing, in a cluster randomised trial (n = 1339 patients), two decision support interventions (DESIs). Both DESIs were used in the intervention arm and each comprised an online risk prediction model, brief decision aid and information booklet. One DESI supported the decision to have either primary endocrine therapy (PET) or surgery with adjuvant therapies and the second supported the decision to have adjuvant chemotherapy after surgery or not.Methods: Sixteen sites were randomly selected to take part in the process evaluation. Multiple methods of data collection were used. Medical Research Council (MRC) guidelines for the evaluation of complex interventions were used.Results: Eighty-two patients, mean age 75.5 (range 70-93), provided data for the process evaluation. Seventy-three interviews were completed with patients. Ten clinicians from six intervention sites took part in telephone interviews. Dose: Ninety-one members of staff in the intervention arm received intervention training. Reach: The online tool was accessed on 324 occasions by 27 clinicians. Reasons for non-use of the online tool were commonly that the patient had already made a decision or that there was no online access in the clinic. Of the 32 women for whom there were data available, fifteen from the intervention arm and six from the usual care arm were offered a choice of treatment. Fidelity: Clinicians used the online tool in different ways, with some using it during the consultation and others checking the online survival estimates before the consultation. Adaptation: There was evidence of adaptation when using the DESIs. A lack of infrastructure, e.g. internet access, was a barrier to the use of the online tool. The brief decision aid was rarely used. Mediators: Shared decision-making: Most patients felt able to contribute to decision-making and expressed high levels of satisfaction with the process. Participants' responses to intervention: Six patients reported the DESIs to be very useful, one somewhat useful and two moderately useful.Conclusions: Clinicians who participated were mainly supportive of the interventions and had attempted some adaptations to make the interventions applicable, but there were practical and engagement barriers that led to sub-optimal adoption in routine practice.Trial Registration: ISRCTN46099296 . Registered on 11 August 2016-retrospectively registered. [ABSTRACT FROM AUTHOR]

The Democratic Republic of Congo (DRC) presents a challenging context in which to respond to public health crises. Its 2018– 2020 Ebola outbreak was the second largest in history. Lessons were known from the previous West African outbreak. Chief among these was the recognition that local action and involvement are key to establishing effective epidemic-response. It remains unclear whether and how this was achieved in DRC's Ebola response. Additionally, there is a lack of scholarship on how to build resilience (the ability to adapt or transform under pressure) in crisis-response. In this article, we critically review literature to examine evidence on whether and how communities were involved, trust built, and resilience strengthened through adaptation or transformation of DRC's 2018– 2020 Ebola response measures. Overall, we found limited evidence that the response adapted to engage and involve local actors and institutions or respond to locally expressed concerns. When adaptations occurred, they were shaped by national and international actors rather than enabling local actors to develop locally trusted initiatives. Communities were "engaged" to understand their perceptions but were not involved in decision-making or shaping responses. Few studies documented how trust was built or analyzed power dynamics between different groups in DRC. Yet, both these elements appear to be critical in building effective, resilient responses. These failures occurred because there was no willingness by the national government or international agencies to concede decision-making power to local people. Emergency humanitarian response is entrenched in highly medicalized, military style command and control approaches which have no space for decentralizing decision-making to "non-experts". To transform humanitarian responses, international responders can no longer be regarded as "experts" who own the knowledge and control the response. To successfully tackle future humanitarian crises requires a transformation of international humanitarian and emergency response systems such that they are led, or shaped, through inclusive, equitable collaboration with local actors. [ABSTRACT FROM AUTHOR]

Background: The 2013–15 Ebola epidemic in West Africa was the largest so far recorded, and mainly affected three adjacent countries, Guinea, Liberia and Sierra Leone. The worst affected country (in terms of confirmed cases) was Sierra Leone. The present paper looks at the epidemic in Sierra Leone. The epidemic in this country was a concatenation of local outbreaks. These local outbreaks are not well characterized through analysis using standard numerical techniques. In part, this reflects difficulties in record collection at the height of the epidemic. This paper offers a different approach, based on application of field-based techniques of social investigation that provide a richer understanding of the epidemic. Methods: In a post-epidemic study (2016–18) of two districts (Bo and Moyamba) we use ethnographic data to reconstruct local infection pathways from evidence provided by affected communities, cross-referenced to records of the epidemic retained by the National Ebola Response Commission, now lodged in the Ebola Museum and Archive at Njala University. Our study documents and discusses local social and contextual factors largely missing from previously published studies. Results: Our major finding is that the epidemic in Sierra Leone was a series of local outbreaks, some of which were better contained than others. In those that were not well contained, a number of contingent factors helps explain loss of control. Several numerical studies have drawn attention to the importance of local heterogeneities in the Sierra Leone Ebola epidemic. Our qualitative study throws specific light on a number of elements that explain these heterogeneities: the role of externalities, health system deficiencies, cultural considerations and local coping capacities. Conclusions: Social issues and local contingencies explain the spread of Ebola in Sierra Leone and are key to understanding heterogeneities in epidemiological data. Integrating ethnographic research into epidemic-response is critical to properly understand the patterns of spread and the opportunities to intervene. This conclusion has significant implications for future interdisciplinary research and interpretation of standard numerical data, and consequently for control of epidemic outbreaks. [ABSTRACT FROM AUTHOR]

This case study focuses on two epidemic diseases in Sierra Leone. Ebola in 2014–15 drew international response, but was contained within the Upper West African region. COVID-19 reached Sierra Leone in April 2020 as part of a global pandemic. Local social knowledge has been an important factor in shaping responses to both diseases. In the case of Ebola, infection was concentrated in families, and responders needed a good knowledge of family interactional dynamics. COVID-19 is a more public disease. Responders have to assess risk factors in workplaces, markets, and places of worship. Comparing and contrasting the two cases also draws attention to different aspects of the historical context. Ebola response indexes Sierra Leone's history as a humanitarian project associated with the abolition of the slave trade. The pandemic challenge of COVID-19 draws attention to Sierra Leone's nodal position within a global diaspora rooted in Atlantic slavery and emancipation. Responders are forced to consider the ways in which the two infections articulate different aspects of calls for global social justice. [ABSTRACT FROM AUTHOR]

Background: Concern has been expressed over how well Africa is prepared to cope with the pandemic of Covid-19. Will rural populations with low levels of education know how to apply community-based infection control? We undertook fieldwork in two villages in central Sierra Leone to gain insight into how rural people faced with Covid-19 assess epidemic infection risks. Methods: Two communities were selected based on prior contrasted exposure to Ebola Virus Disease–one with substantial number of cases and the other having resisted infection through strong community sequestration measures. We assessed understanding of infection risks via an experimental game. This asked players to express a preference for one of two diseases, one resembling Ebola with lower risk of infection and the other resembling Covid-19 with lower risk of death. Players were not told the identity of the diseases. Results: In total 107 adult villagers played the game (58% women). Half (52%) preferred the disease model with lower risk of infection, 29% preferred the model with lower risk of death, while 21% saw the combined risk of infection and death as being equivalent. Differences in reactions between the two locations were small despite different experiences of Ebola. Asked to explain their choices 48% of players cited information on infection risks modelled by the game and 31% stated that their choices reflected awareness of the need for personal action and respect for local regulations. We concluded that villagers thoughtfully assess disease risks and that some are good intuitive statisticians. Conclusions: Results suggest rural people in Sierra Leone retain the lessons of experience from the Ebola outbreak of 2014–15 and will be able to apply these lessons to a new infectious disease for which have no prior practical experience. Our expectation is that rural populations will understand Covid-19 control measures, thus reducing need for draconian enforcement. [ABSTRACT FROM AUTHOR]

During the 2014-2015 Ebola epidemic in Sierra Leone, people were required by law to call a trained "safe burial" team to dispose of the body of a person who had died from Ebola. It took days for a team to arrive, however, due to limited resources and rural travel obstacles, so some villagers felt obliged to bury their loved ones themselves. Even with timely arrival of a team, there can be cultural priorities that deserve attention. One man's case discussed in this article suggests the need for Ebola responders to consider villagers' perspectives and possibilities for compromise. [ABSTRACT FROM AUTHOR]

The paper considers local responses to the introduction of an Ebola Treatment Centre in eastern Sierra Leone during the West African epidemic of 2014–15. Our study used qualitative methods consisting of focus groups and interviews, to gather responses from patients, members of the families of survivors and deceased victims of the disease, social liaison workers from the centre, and members of the general public. The data indicate that scepticism and resistance were widespread at the outset, but that misconceptions were replaced, in the minds of those directly affected by the disease, by more positive later assessments. Social workers, and social contacts of families with workers in the centre, helped reshape these perceptions, but a major factor was direct experience of the disease. This is apparent in the positive endorsements by survivors and families who had members taken to the facility. Even relatives of deceased victims agreed that the case-handling centre was valuable. However, we also present evidence of continuing scepticism in the minds of members of the general public, who continue to suspect that Ebola was a crisis manufactured for external benefit. Our conclusions stress the importance of better connectivity between communities and Ebola facilities to facilitate experiential learning. There is also a need to address the wider cognitive shock caused by a well-funded Ebola health initiative arriving in communities with a long history of inadequate health care. Restoring trust in medicine requires Ebola Virus Disease to be re-contextualized within a broader framework of concern for the health of all citizens. [ABSTRACT FROM AUTHOR]

Conservation planning for protected species often relies on estimates of life‐history parameters. A commonly used parameter is the instantaneous maximum population growth rate (rmax) that can be used to limit removals and design recovery targets. Estimation of rmax can be challenging because of limited availability of species‐ and population‐specific data and life‐history information. We applied a method proposed by Neil and Lebreton, originally developed for birds, to loggerhead turtles. The method uses age‐at‐first‐reproduction and adult survival to estimate rmax. We used a variety of datasets and matrix population models to confirm an allometric assumption required by the method, and to generate estimates of age‐at‐first‐reproduction and adult survival. A meta‐analysis was applied to parameters from reported growth curves, which were then combined with the size distribution of neophyte nesters to derive estimates of age‐at‐first‐reproduction. Adult survival rates were obtained from an existing matrix population model. Monte Carlo simulation was then used to combine the estimates of the allometric coefficients, age‐at‐first‐reproduction, and adult survival to obtain a probability distribution of approximate rmax values. Estimated annual maximum population growth rates averaged 0.024, with a mode of 0.017 and a 95% highest density interval of 0.006–0.047. These estimates were similar to values reported by others using different methods and captured the variability in positive, annual change estimates across nesting beach sites for the northwest Atlantic loggerhead population. The use of life‐history parameters has a long history in wildlife and fisheries management and conservation planning. Our estimates of rmax, while having some biases and uncertainty, encompassed values presently used in recovery planning for loggerhead turtles and offer additional information for the management of endangered and threatened species. [ABSTRACT FROM AUTHOR]

Most steel moment frames are designed so that the beams act as structural fuses during earthquake loading. This approach, while effective for life safety, has poor resilience because it is difficult to replace beams in a building. A repairable steel moment frame connection has been developed that may be attractive to engineers and constructors. The connection has a fuse plate bolted to the beam bottom flange which experiences shear yielding during severe earthquakes, protecting both the column and the beam. After an earthquake, the fuse plates can be removed and replaced to unlock residual frame deformations and prepare the building for another event. Full‐scale experiments were conducted to validate the performance of this repairable connection. Two tests were performed with a W690×125 beam and a W530×196 column. The tests demonstrated rotation capacities of at least 0.05 rad, which exceeded AISC requirements for special moment frames. The fuse plate was effective in preventing beam damage in each test, and the second test demonstrated that the connection could be repaired by replacing the fuse plate. [ABSTRACT FROM AUTHOR]

Enteroendocrine cells (EECs) produce hormones such as glucagon-like peptide 1 and peptide YY that regulate food absorption, insulin secretion, and appetite. Based on the success of glucagon-like peptide 1-based therapies for type 2 diabetes and obesity, EECs are themselves the focus of drug discovery programs to enhance gut hormone secretion. The aim of this study was to identify the transcriptome and peptidome of human EECs and to provide a cross-species comparison between humans and mice. By RNA sequencing of human EECs purified by flow cytometry after cell fixation and staining, we present a first transcriptomic analysis of human EEC populations and demonstrate a strong correlation with murine counterparts. RNA sequencing was deep enough to enable identification of low-abundance transcripts such as G-protein-coupled receptors and ion channels, revealing expression in human EECs of G-protein-coupled receptors previously found to play roles in postprandial nutrient detection. With liquid chromatography-tandem mass spectrometry, we profiled the gradients of peptide hormones along the human and mouse gut, including their sequences and posttranslational modifications. The transcriptomic and peptidomic profiles of human and mouse EECs and cross-species comparison will be valuable tools for drug discovery programs and for understanding human metabolism and the endocrine impacts of bariatric surgery. [ABSTRACT FROM AUTHOR]

Correction to: I Nature Communications i https://doi.org/10.1038/s41467-023-40061-y, published online 24 July 2023 In this article the author name R. C. Coombes was incorrectly written as R. Charles Coombes. The original article can be found online at https://doi.org/10.1038/s41467-023-40061-y. [Extracted from the article]

Purpose: The Janus-associated kinase (JAK)/signal transducer and activator of transcription pathway is a key regulator of inflammatory signaling, associated with tumorigenesis, cell survival, and progression. This randomized phase 2 trial evaluated the efficacy and safety of the addition of ruxolitinib, a JAK1/JAK2 inhibitor, to capecitabine in patients with HER2-negative advanced breast cancer and high systemic inflammation (modified Glasgow Prognostic Score [mGPS] ≥ 1).Methods: Patients with ≤ 2 prior chemotherapy regimens for advanced or metastatic disease or hormone receptor-positive patients with disease progression on prior hormonal therapies were randomized 1:1 to 21-day cycles of ruxolitinib (n = 76) or placebo (n = 73) plus capecitabine. The primary endpoint was overall survival (OS).Results: Baseline characteristics were well balanced between groups. For ruxolitinib plus capecitabine versus placebo plus capecitabine, median OS was 11.2 months versus 10.9 months (log-rank test P = 0.762); median progression-free survival (PFS) was 4.5 months versus 2.5 months (log-rank test P = 0.151); and overall response rate (ORR) was 28.9% versus 13.7% (Cochran-Mantel-Haenszel test P = 0.024), respectively. A more favorable change in health-related quality of life (HRQoL) was observed with ruxolitinib plus capecitabine versus placebo plus capecitabine. Both regimens were generally tolerable. A higher incidence of grade 3/4 anemia (25.4% vs 5.6%) and a lower incidence of grade 3/4 palmar-plantar erythrodysesthesia (1.4% vs 12.7%) occurred with ruxolitinib plus capecitabine versus placebo plus capecitabine.Conclusions: The addition of ruxolitinib to capecitabine for patients with advanced breast cancer and high systemic inflammation was generally tolerable; ORR was numerically greater, a more favorable change in HRQoL was observed, but neither OS nor PFS was improved compared with placebo plus capecitabine. [ABSTRACT FROM AUTHOR]

Purpose: The phase 3 MONALEESA-2 study demonstrated that addition of ribociclib (RIB) to letrozole (LET) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC). Here, we evaluated duration of response (DoR), tumor shrinkage, PFS by treatment-free interval (TFI), and health-related quality of life (HRQoL).Methods: Postmenopausal women (N = 668) with HR+ , HER2− ABC and no prior systemic therapy for ABC were randomized to RIB (600 mg/day; 3 weeks on/1 week off) plus LET (2.5 mg/day; continuous) or placebo (PBO) plus LET. Primary end point was PFS; HRQoL was the secondary end point; DoR was exploratory end point and PFS by TFI was post hoc analysis.Results: Of 501 pts with measurable disease and confirmed complete or partial response, median DoR was 26.7 months (95% CI, 24.0-NR) in the RIB arm versus 18.6 months (95% CI, 14.8-23.1) in the PBO arm. At 8 weeks, more pts in the RIB arm (32%) versus the PBO arm (17%) experienced best percentage change ≥ 60%. The average pain reduction was greater in the RIB arm (26%) versus the PBO arm (15%). PFS benefit was seen with RIB vs PBO, irrespective of TFI.Conclusion: RIB plus LET versus PBO plus LET is associated with earlier and more durable tumor response, greater degree of tumor shrinkage and pain reduction, and PFS benefit irrespective of TFI. These data further support RIB plus LET as a first-line treatment option for postmenopausal women with HR+ , HER2− ABC. [ABSTRACT FROM AUTHOR]

Although the mechanisms by which glucose regulates insulin secretion from pancreatic β-cells are now well described, the way glucose modulates gene expression in such cells needs more understanding. Here, we demonstrate that MondoA, but not its paralog carbohydrate-responsive element-binding protein, is the predominant glucose-responsive transcription factor in human pancreatic β-EndoC-βH1 cells and in human islets. In high-glucose conditions, MondoA shuttles to the nucleus where it is required for the induction of the glucose-responsive genes arrestin domain-containing protein 4 (ARRDC4) and thioredoxin interacting protein (TXNIP), the latter being a protein strongly linked to β-cell dysfunction and diabetes. Importantly, increasing cAMP signaling in human β-cells, using forskolin or the glucagon-like peptide 1 mimetic Exendin-4, inhibits the shuttling of MondoA and potently inhibits TXNIP and ARRDC4 expression. Furthermore, we demonstrate that silencing MondoA expression improves glucose uptake in EndoC-βH1 cells. These results highlight MondoA as a novel target in β-cells that coordinates transcriptional response to elevated glucose levels. [ABSTRACT FROM AUTHOR]