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Abstract Background The use of antiretroviral (ARV) drugs in Tanzania has led to a significant reduction in morbidity and mortality and improved quality of life among people living with HIV infection. However, the ease of access and availability of the drugs has, in some cases, led to misuse of the ARV in areas such as animal farming, posing a risk of the emergence of ARV resistance. The study’s objective was to investigate the use of ARV in animal farming and the factors associated with ARV use. We conducted a cross-sectional study in three regions (Dar es Salaam, Iringa, and Mbeya) using focus group discussions. The researchers used NVivo 12 software for qualitative data analysis. Results A total of 113 participants participated in this study. The participants mentioned the use of veterinary, human, and local medicines to be prevalent. The drivers for such usage are disease treatment and prevention, growth promotion, counterfeited drugs, higher cost of animal feeds, profit maximization, market competition, advice from veterinary drug sellers, and easy availability and accessibility of medicines. New Castle, respiratory diseases, and diarrhea were the most common diseases affecting broiler chickens, while limb paralysis, swine fever, and skin diseases were prominent in domestic pigs. The Dar es Salaam region has a scarcity of extension officers compared to the Mbeya and Iringa regions. Almost all FGD participants reported hearing about the use of ARVs and family planning injectable and pills. Some of the participants agreed to use these drugs for growth promotion since they are effective. Conclusion High usage of veterinary, human, and other medicines, including ARVs, in animal production predisposes the Tanzanian community to public health threats, including antibiotic and antiretroviral resistance. We recommend implementing urgent mitigation strategies to control the misuse of human ARVs in animal production.

Abstract Large-scale modes of climate variability, such as the El Niño-Southern Oscillation, North Atlantic Oscillation, and Indian Ocean Dipole, show significant regional correlations with seasonal weather conditions, and are routinely forecast by meteorological agencies attempting to anticipate seasonal precipitation patterns. Here, we use machine learning together with more traditional approaches to quantify how much precipitation variability can be explained by large-scale modes of variability, and to understand the degree to which these modes interact non-linearly. We find that the relationship between climate modes and precipitation is predominantly non-linear. In some regions and seasons climate modes can explain up to 80% of precipitation variability. However, variability explained is below 10% for more than half of the land surface, and only 1% of the land shows values above 50%. This outcome provides a clear rationale to limit expectations of predictability from modes of variability in all but a few select regions and seasons.

The field of extreme event attribution (EEA) has rapidly developed over the last two decades. Various methods have been developed and implemented, physical modelling capabilities have generally improved, the field of impact attribution has emerged, and assessments serve as a popular communication tool for conveying how climate change is influencing weather and climate events in the lived experience. However, a number of non-trivial challenges still remain that must be addressed by the community to secure further advancement of the field whilst ensuring scientific rigour and the appropriate use of attribution findings by stakeholders and associated applications. As part of a concept series commissioned by the World Climate Research Programme, this article discusses contemporary developments and challenges over six key domains relevant to EEA, and provides recommendations of where focus in the EEA field should be concentrated over the coming decade. These six domains are: (1) observations in the context of EEA; (2) extreme event definitions; (3) statistical methods; (4) physical modelling methods; (5) impact attribution; and (6) communication. Broadly, recommendations call for increased EEA assessments and capacity building, particularly for more vulnerable regions; contemporary guidelines for assessing the suitability of physical climate models; establishing best-practice methodologies for EEA on compound and record-shattering extremes; co-ordinated interdisciplinary engagement to develop scaffolding for impact attribution assessments and their suitability for use in broader applications; and increased and ongoing investment in EEA communication. To address these recommendations requires significant developments in multiple fields that either underpin (e.g., observations and monitoring; climate modelling) or are closely related to (e.g., compound and record-shattering events; climate impacts) EEA, as well as working consistently with experts outside of attribution and climate science more generally. However, if approached with investment, dedication, and coordination, tackling these challenges over the next decade will ensure robust EEA analysis, with tangible benefits to the broader global community.

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 had axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis showed that loss of Ntn1 did not affect bifurcation but rather altered turning angles. To distinguish their guidance functions, we examined mice with triple deletion of Ntn1, Slit1, and Slit2 and found a completely disorganized dorsal funiculus. Comparing mice with different genotypes using immunolabeling and single axon tracing revealed additive guidance errors, demonstrating the independent roles of Ntn1 and Slit. Moreover, the same defects were observed in embryos lacking their cognate receptors. These in vivo studies thus demonstrate the presence of multi-factorial guidance mechanisms that ensure proper formation of a common branched axonal structure during spinal cord development.

Abstract An additional deposition step was added to a multi-step electron beam lithographic fabrication process to unlock the height dimension as an accessible parameter for resonators comprising unit cells of quasi-bound states in the continuum metasurfaces, which is essential for the geometric design of intrinsically chiral structures.

Abstract Background Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25–60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. Methods Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. Discussion This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. Trial registration ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Abstract Global gridded data sets of observed extremes indices underpin assessments of changes in climate extremes. However, similar efforts to enable the assessment of indices relevant to different sectors of society have been missing. Here we present a data set of sector‐specific indices, based on daily station data, that extends the HadEX3 data set of climate extremes indices. These additional indices, which can be used singly or in combinations, have been recommended by the World Meteorological Organization and are intended to empower decision makers in different sectors with accurate historical information about how sector‐relevant measures of the climate are changing, especially in regions where in situ daily temperature and rainfall data are hard to come by. The annual and/or monthly indices have been interpolated on to a 1.875° × 1.25° longitude‐latitude grid for 1901–2018. We show changes in globally‐averaged time series of these indices in comparison with reanalysis products. Changes in temperature‐based indices are consistent with global scale warming, with days with Tmax > 30°C (TXge30) increasing virtually everywhere with potential impacts on crop fertility. At the other end of the scale, the number of days with Tmin

Abstract INTRODUCTION Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test. METHODS The target population for the Study of Latinos‐Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage‐adjusted DSS scores, and percentile cut‐points were created using survey‐adjusted regression and quantile regression models. RESULTS Age, education, sex, heritage, and language preference were associated with DSS scores. DISCUSSION Significant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard. Highlights Normative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos‐Investigation of Neurocognitive Aging (SOL‐INCA) This study is the first to develop norms for the DSS test across four regions of the United States. Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed. We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst_shiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults.

Abstract Introduction We investigated cognitive profiles among diverse, middle‐aged and older Hispanic/Latino adults in the Study of Latinos–Investigation of Neurocognitive Aging (SOL‐INCA) cohort using a cross‐sectional observational study design. Methods Based on weighted descriptive statistics, the average baseline age of the target population was 56.4 years, slightly more than half were women (54.6%), and 38.4% reported less than a high school education. We used latent profile analysis of demographically adjusted z scores on SOL‐INCA neurocognitive tests spanning domains of verbal memory, language, processing speed, and executive function. Results Statistical fit assessment indices combined with clinical interpretation suggested five profiles: (1) a Higher Global group performing in the average‐to‐high‐average range across all cognitive and instrumental activity of daily living (IADL) tests (13.8%); (2) a Higher Memory group with relatively high performance on memory tests but average performance across all other cognitive/IADL tests (24.6%); (3) a Lower Memory group with relatively low performance on memory tests but average performance across all other cognitive/IADL tests (32.8%); (4) a Lower Executive Function group with relatively low performance on executive function and processing speed tests but average‐to‐low‐average performance across all other cognitive/IADL tests (16.6%); and (5) a Lower Global group performing low‐average‐to‐mildly impaired across all cognitive/IADL tests (12.1%). Discussion Our results provide evidence of heterogeneity in the cognitive profiles of a representative, community‐dwelling sample of diverse Hispanic/Latino adults. Our analyses yielded cognitive profiles that may assist efforts to better understand the early cognitive changes that may portend Alzheimer's disease and related dementias among diverse Hispanics/Latinos. Highlights The present study characterized cognitive profiles among diverse middle‐aged and older Hispanic/Latino adults. Latent profile analysis of neurocognitive test scores was the primary analysis conducted. The target population consists of middle‐aged and older Hispanic/Latino adults enrolled in the Hispanic Community Health Study/Study of Latinos and ancillary Study of Latinos ‐ Investigation of Neurocognitive Aging.

Abstract The high latitude Southern Hemisphere (SH) is an important region for Earth's climate. Ocean heat content, cryosphere interactions, Antarctic bottom water development and the cloud‐albedo feedbacks need to be understood to form a complete picture of the climate system. However, the high latitude SH is one of the most under‐observed regions due to its remoteness. The advent of satellites and reanalyses have improved our monitoring of this region. Some previous studies observed an increase in precipitation over the SH high latitudes, however we argue that some of the trends in commonly used data sets may be artifacts. We use regression analysis of trends in precipitation and the Southern Annular Mode to contrast these relationships in satellite and reanalysis products, and to evaluate precipitation over the SH. We suggest that sensor changes and the lack of in situ data available for calibration may be responsible for unusual precipitation patterns especially around 65°S.

Abstract Millions of sub‐daily sea‐level pressure observations taken between 1919 and 1960 over the British and Irish Isles were transcribed from paper records in the early 2000s but were not published and subsequently forgotten. A chance discussion led to the rediscovery of the transcribed data and 5.47 million observations from 160 locations are now made available, although the data have not been fully quality‐controlled. Much of the data are 3‐hourly, allowing for detailed examinations of synoptic weather variations for this region and time period, and will be invaluable for constraining future reanalyses. We illustrate the value of the data using a stormy period during October and November 1928 and discuss the remaining quality‐control issues.

Abstract Background The Veterans Affairs (VA) Clinical Resource Hub (CRH) program aims to improve patient access to care by implementing time-limited, regionally based primary or mental health staffing support to cover local staffing vacancies. VA’s Office of Primary Care (OPC) designed CRH to support more than 1000 geographically disparate VA outpatient sites, many of which are in rural areas, by providing virtual contingency clinical staffing for sites experiencing primary care and mental health staffing deficits. The subsequently funded CRH evaluation, carried out by the VA Primary Care Analytics Team (PCAT), partnered with CRH program leaders and evaluation stakeholders to develop a protocol for a six-year CRH evaluation. The objectives for developing the CRH evaluation protocol were to prospectively: 1) identify the outcomes CRH aimed to achieve, and the key program elements designed to achieve them; 2) specify evaluation designs and data collection approaches for assessing CRH progress and success; and 3) guide the activities of five geographically dispersed evaluation teams. Methods The protocol documents a multi-method CRH program evaluation design with qualitative and quantitative elements. The evaluation’s overall goal is to assess CRH’s return on investment to the VA and Veterans at six years through synthesis of findings on program effectiveness. The evaluation includes both observational and quasi-experimental elements reflecting impacts at the national, regional, outpatient site, and patient levels. The protocol is based on program evaluation theory, implementation science frameworks, literature on contingency staffing, and iterative review and revision by both research and clinical operations partners. Discussion Health systems increasingly seek to use data to guide management and decision-making for newly implemented clinical programs and policies. Approaches for planning evaluations to accomplish this goal, however, are not well-established. By publishing the protocol, we aim to increase the validity and usefulness of subsequent evaluation findings. We also aim to provide an example of a program evaluation protocol developed within a learning health systems partnership.

Objective Chronic pain disproportionately affects medically and psychosocially complex patients, many of whom are at high risk of hospitalisation. Pain prevalence among high-risk patients, however, is unknown, and pain is seldom a focus for improving high-risk patient outcomes. Our objective is to (1) evaluate pain frequency in a high-risk patient population and (2) identify intensive management (IM) programme features that patients and providers perceive as important for promoting patient-centred pain care within primary care (PC)-based IM.Design Secondary observational analysis of quantitative and qualitative evaluation data from a multisite randomised PC-based IM programme for high-risk patients.Setting Five integrated local Veterans Affairs (VA) healthcare systems within distinct VA administrative regions.Participants Staff and high-risk PC patients in the VA.Intervention A multisite randomised PC-based IM programme for high-risk patients.Outcome measures (a) Pain prevalence based on VA electronic administrative data and (b) transcripts of interviews with IM staff and patients that mentioned pain.Results Most (70%, 2593/3723) high-risk patients had at least moderate pain. Over one-third (38%, 40/104) of the interviewees mentioned pain or pain care. There were 89 pain-related comments addressing IM impacts on pain care within the 40 interview transcripts. Patient-identified themes were that IM improved communication and responsiveness to pain. PC provider-identified themes were that IM improved workload and access to expertise. IM team member-identified themes were that IM improved pain care coordination, facilitated non-opioid pain management options and mitigated provider compassion fatigue. No negative IM impacts on pain care were mentioned.Conclusions Pain is common among high-risk patients. Future IM evaluations should consider including a focus on pain and pain care, with attention to impacts on patients, PC providers and IM teams.

Pain associated with breast cancer is a prevalent problem that negatively affects quality of life. Breast cancer pain is not limited to the disease course itself but is also induced by current therapeutic strategies. This, combined with the increasing number of patients living with breast cancer, make pain management for breast cancer patients an increasingly important area of research. This narrative review presents a summary of pain associated with breast cancer, including pain related to the cancer disease process itself and pain associated with current therapeutic modalities including radiation, chemotherapy, immunotherapy, and surgery. Current pain management techniques, their limitations, and novel analgesic strategies are also discussed.

ABSTRACTEnterohemorrhagic Escherichia coli (EHEC) is a major cause of severe bloody diarrhea, with potentially lethal complications, such as hemolytic uremic syndrome. In humans, EHEC colonizes the colon, which is also home to a diverse community of trillions of microbes known as the gut microbiota. Although these microbes and the metabolites that they produce represent an important component of EHEC’s ecological niche, little is known about how EHEC senses and responds to the presence of gut microbiota metabolites. In this study, we used a combined RNA-Seq and Tn-Seq approach to characterize EHEC’s response to metabolites from an in vitro culture of 33 human gut microbiota isolates (MET-1), previously demonstrated to effectively resolve recurrent Clostridioides difficile infection in human patients. Collectively, the results revealed that EHEC adjusts to growth in the presence of microbiota metabolites in two major ways: by altering its metabolism and by activating stress responses. Metabolic adaptations to the presence of microbiota metabolites included increased expression of systems for maintaining redox balance and decreased expression of biotin biosynthesis genes, reflecting the high levels of biotin released by the microbiota into the culture medium. In addition, numerous genes related to envelope and oxidative stress responses (including cpxP, spy, soxS, yhcN, and bhsA) were upregulated during EHEC growth in a medium containing microbiota metabolites. Together, these results provide insight into the molecular mechanisms by which pathogens adapt to the presence of competing microbes in the host environment, which ultimately may enable the development of therapies to enhance colonization resistance and prevent infection.

Rates of reported cases of syphilis have steadily increased since 2000 in the United States. However, despite the increase in cases, mortality from 2000–2014 declined. The following study examines the latest trends in syphilis-related deaths using 2015–2020 Multiple Cause of Death data. A total of 925 syphilis-related deaths were identified during the study period, 30% of which listed syphilis as the underlying cause of death. On average, age-adjusted syphilis mortality increased by 9.51% annually (95% CI = 5.41%–13.77%). Study findings indicate a marked increase in deaths attributed to syphilis, underscoring the need to more systematically and comprehensively address the growing sexually transmitted infection epidemic in the United States.

Fisher et al. combine sediment geochemistry and climate modelling to reveal long-term synchrony between erosion rates and orbitally-driven climate oscillations in the tectonically-active southern Central Andes.

Hybrid integrated diode lasers based on combining semiconductor optical amplifiers with low-loss Si$_{3}$N$_{4}$-based feedback circuits enable great laser performance for advanced photonic circuits. In particular, using high-Q Si$_{3}$N$_{4}$ ring resonators for frequency-selective feedback provides wide spectral coverage, mode-hop free tuning, and high frequency stability on short timescales, showing as ultra-narrow intrinsic linewidths. However, many applications also require long-term stability, which can be provided by locking the laser frequency to a suitable reference. We present the stabilization of a hybrid-integrated laser, which is widely tunable around the central wavelength of 1550 nm, to a fiber-based optical frequency discriminator (OFD) and to an acetylene absorption line. By locking the laser to the OFD, the laser's fractional frequency stability is improved down to $1.5\cdot 10^{-12}$ over an averaging time of 0.5 ms. For absolute stability over longer times of several days, we successfully lock the laser frequency to an acetylene absorption line. This limits the frequency deviations of the laser to a range of less than 12 MHz over 5 days.

IntroductionChronic pain negatively impacts a range of sensory and affective behaviors. Previous studies have shown that the presence of chronic pain not only causes hypersensitivity at the site of injury but may also be associated with pain-aversive experiences at anatomically unrelated sites. While animal studies have indicated that the cingulate and prefrontal cortices are involved in this generalized hyperalgesia, the mechanisms distinguishing increased sensitivity at the site of injury from a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs are not well known.MethodsWe compared measured pain responses to peripheral mechanical stimuli applied to a site of chronic pain and at a pain-free site in participants suffering from chronic lower back pain (n = 15) versus pain-free control participants (n = 15) by analyzing behavioral and electroencephalographic (EEG) data.ResultsAs expected, participants with chronic pain endorsed enhanced pain with mechanical stimuli in both back and hand. We further analyzed electroencephalographic (EEG) recordings during these evoked pain episodes. Brain oscillations in theta and alpha bands in the medial orbitofrontal cortex (mOFC) were associated with localized hypersensitivity, while increased gamma oscillations in the anterior cingulate cortex (ACC) and increased theta oscillations in the dorsolateral prefrontal cortex (dlPFC) were associated with generalized hyperalgesia.DiscussionThese findings indicate that chronic pain may disrupt multiple cortical circuits to impact nociceptive processing.

IntroductionSmall cell lung cancer (SCLC) is a rapidly growing malignancy with early distant metastases. Up to 70% will develop brain metastases, and the poor prognosis of these patients has not changed considerably. The potential of checkpoint inhibitors (CPI) in treating recurrent (r/r) SCLC and their effect on brain metastases remain unclear.MethodsIn this retrospective multicenter study, we analyzed r/r SCLC patients receiving second or further-line CPI versus chemotherapy between 2010 and 2020. We applied multivariable-adjusted Cox regression analysis to test for differences in 1-year mortality and real-world progression. We then used interaction analysis to evaluate whether brain metastases (BM) and/or cranial radiotherapy (CRT) modified the effect of CPI versus chemotherapy on overall survival.ResultsAmong 285 patients, 99 (35%) received CPI and 186 (65%) patients received chemotherapy. Most patients (93%) in the CPI group received nivolumab/ipilimumab. Chemotherapy patients were entirely CPI-naïve and only one CPI patient had received atezolizumab for first-line treatment. CPI was associated with a lower risk of 1-year mortality (adjusted Hazard Ratio [HRadj] 0.59, 95% CI 0.42 to 0.82, p=0.002). This benefit was modified by BM and CRT, indicating a pronounced effect in patients without BM (with CRT: HRadj 0.34, p=0.003; no CRT: HRadj 0.50, p=0.05), while there was no effect in patients with BM who received CRT (HRadj 0.85, p=0.59).ConclusionCPI was associated with a lower risk of 1-year mortality compared to chemotherapy. However, the effect on OS was significantly modified by intracranial disease and radiotherapy, suggesting the benefit was driven by patients without BM.

Machine learning is becoming an increasingly common component of routine data analyses in clinical research. The past decade in pain research has witnessed great advances in human neuroimaging and machine learning. With each finding, the pain research community takes one step closer to uncovering fundamental mechanisms underlying chronic pain and at the same time proposing neurophysiological biomarkers. However, it remains challenging to fully understand chronic pain due to its multidimensional representations within the brain. By utilizing cost-effective and non-invasive imaging techniques such as electroencephalography (EEG) and analyzing the resulting data with advanced analytic methods, we have the opportunity to better understand and identify specific neural mechanisms associated with the processing and perception of chronic pain. This narrative literature review summarizes studies from the last decade describing the utility of EEG as a potential biomarker for chronic pain by synergizing clinical and computational perspectives.

Background Therapeutic relational connection (TRC) in telehealth is a new concept that refers to the intentional use of relationship connection between health care providers and their patients as both parties work toward a therapeutic aim. It has been demonstrated that TRC positively affects patient-centered outcomes including adherence, self-management, and satisfaction with care. What is not known are best practices for establishing TRC during telehealth visits. The rapid emergence of telehealth during the COVID-19 pandemic has identified a number of challenges. These challenges include lack of human contact, distance creating mistrust, the inability to rely on nonverbal communication, and a sense of depersonalization. Training for health care providers in these interpersonal communication skills needed to establish TRC during telehealth visits is needed. Objective This paper aims to explore the evolutionary concept of TRC in telehealth. The purpose of this paper is to provide a concept analysis of TRC during telehealth interactions between providers and patients through a comprehensive review of the existing published literature. Methods Rodgers’ evolutionary concept analysis method was used to guide this study. PubMed, Embase, PsycINFO, and CINAHL were used to search for relevant publications. An integrative review strategy aided by Rayyan software was used to identify a final sample of 13 papers for analysis. Results The proposed definition of TRC in telehealth is the experience of a mutually responsive patient-provider relationship that is built on mutual respect and understanding and informed by cultural humility, presence, empathy, and the ability to effectively evaluate patient concerns to work toward a therapeutic aim. The key attributes of TRC in telehealth are the provider’s ability to evaluate patient concerns, interpersonal communication, cultural humility, mutual trust and respect, presence, empathy, and building relationships. Clinical presence, proper environment, knowledge about the use of technology (both patient and provider), use of verbal and nonverbal communication, and knowledge about community and culture are important antecedents of TRC. Consequences of TRC include improved communication resulting in mutual respect and caring, adherence to follow-up recommendations, increased coping, collaborative decision-making, and satisfaction with care. Conclusions Telehealth visits necessitate alternative approaches to establishing TRC as compared to in-person clinic visits. With the rapid expansion of telehealth platforms and a heightened acceptance of the technology, there is a need to integrate knowledge and provide a clear conceptualization of TRC in telehealth as TRC has been demonstrated to result in positive patient-centered outcomes. Identifying the attributes and antecedents of TRC in telehealth allows us the opportunity to develop guidelines and educational interventions aimed at training health care providers in the skills needed to establish TRC during telehealth visits.

Aim: To contextualize the effectiveness of tisagenlecleucel versus real-world standard of care (SoC) in relapsed/refractory follicular lymphoma. Materials & methods: A retrospective indirect matched comparison study using data from the phase II ELARA trial and the US Flatiron Health Research Database. Results: Complete response rate was 69.1 versus 17.7% and the overall response rate was 85.6 versus 58.1% in tisagenlecleucel versus SoC, post weighting by odds. For overall survival, an estimated reduction in the risk of death was observed in favor of tisagenlecleucel over SoC. The hazard ratio for progressionfree survival was 0.45 (95% CI: 0.26, 0.88), and for time-to-next treatment was 0.34 (95% CI: 0.15, 0.78) with tisagenlecleucel versus SoC. Conclusion: A consistent trend toward improved efficacy end points was observed in favor of tisagenlecleucel versus SoC.

Background: Aloe ferox is an indigenous medicinal plant that is widely used for its various medicinal and pharmacological properties. Despite the medicinal importance and various applications of the species, it is surprising that little is known about the extent of geographical differences in its major chemical compounds. Also, the correlation between different geographic regions and variations in plant phytochemicals has received less attention. Aim: This study sought to investigate the presence of biologically active compounds in the leaf extracts of A. ferox from different geographical regions across South Africa. Setting: This study was set in different regions within South Africa. Methods: Phytochemical screening was performed qualitatively using established standard procedures involving chemical reagents such as hexane, chloroform and methanol and a series of reactions to determine the presence of phytocompounds of biological importance. Results: The study revealed that A. ferox leaves possess several classes of phytocompounds such as alkaloids, tannins, terpenoids, glycosides, phenolics, flavonoids, saponins and fixed oils and fats across various samples. Mucilage was absent across the samples. Conclusion: The study revealed eight classes of phytochemical compounds present on A. ferox leaves in three different geographic regions, which is consistent with the previous studies; however, further research is needed to enhance the study through qualitative research, gas chromatography–mass spectrometry and high-performance liquid chromatography analyses to validate phytochemical variations and their therapeutic effects. Contribution: This study contributes to the existing knowledge of the therapeutic Aloe genus.

Brainstem olivocochlear neurons (OCNs) modulate the earliest stages of auditory processing through feedback projections to the cochlea and have been shown to influence hearing and protect the ear from sound-induced damage. Here, we used single-nucleus sequencing, anatomical reconstructions, and electrophysiology to characterize murine OCNs during postnatal development, in mature animals, and after sound exposure. We identified markers for known medial (MOC) and lateral (LOC) OCN subtypes, and show that they express distinct cohorts of physiologically relevant genes that change over development. In addition, we discovered a neuropeptide-enriched LOC subtype that produces Neuropeptide Y along with other neurotransmitters. Throughout the cochlea, both LOC subtypes extend arborizations over wide frequency domains. Moreover, LOC neuropeptide expression is strongly upregulated days after acoustic trauma, potentially providing a sustained protective signal to the cochlea. OCNs are therefore poised to have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.

ObjectiveGiven that several non-cognitive factors can contribute to difficulties with everyday functioning, examining the extent to which cognition is associated with brain-related changes in everyday functioning is critical to accurate characterization of cognitive disorders. In this study, we examined neuropsychological correlates of the shared variance between everyday functioning and pathological indicators of cognitive aging using MRI brain volumetrics.Participants and methodsParticipants were 600 adults aged 55 and older without dementia [432 cognitively normal; 168 mild cognitive impairment (MCI)] from the National Alzheimer’s Coordinating Center cohort who underwent neuropsychological testing, informant-rated everyday functioning, and brain MRI scanning at baseline. The shared variance between everyday functioning and brain volumetrics (i.e., hippocampal volume, white matter hyperintensity volume) was extracted using the predicted value from multiple regression. The shared variance was used as an indicator of pathological everyday functional impairment. The residual variance from the regression analysis was used to examine functional reserve.ResultsLarger white matter hyperintensity volumes (p = 0.002) and smaller hippocampal volumes (p

Abstract Atmospheric warming results in an intensification of annual precipitation over the globe but large uncertainties remain regionally and at seasonal scales, especially for extremes. Using 29 models from the Sixth Phase of the Coupled Model Intercomparison Project (CMIP6), we investigate future seasonal changes in extreme precipitation (under the scenario SSP5‐8.5) and how it compares to changes in mean precipitation. Over land, we find a strong intensification of the wettest day in all seasons over the mid and high latitudes of the Northern Hemisphere and over India during the monsoon. Extreme intensity decreases in the subtropics for some seasons, including over large regions around the Mediterranean basin and Southern Africa, and these drying patterns are not apparent in annual results. The key finding is that the CMIP6 multi‐model mean always shows that seasonal changes in mean and extreme precipitation align where there is high model agreement. That is, in all seasons by the end of the 21st century, extremes intensify in regions where mean precipitation increases and decline where mean precipitation decreases. This should not hide inherent uncertainties associated, namely the large range of changes intensity that can be found across the models, and an important modulation of the changes by internal variability. Yet, this study shows that the multi‐model mean shows broad consistency such that future seasonal changes in mean precipitation could be used to infer future changes in extremes (and vice versa), thus providing valuable information for risk planning and mitigation strategies.

Monitoring changes in climate extremes is vitally important in order to provide context for both our current and possible future climates. Datasets based on climate extremes indices from in situ observations and climate reanalyses are often used for this purpose. We assess the spatial and temporal consistency between these two classes of dataset on a global basis to understand where they agree or are complementary. As expected, the temperature time series expressed as anomalies, or self-normalizing indices, agree well. While there is sometimes a large spread in absolute values between products, both long-term trends and inter-annual variability are also in agreement. Spatially the temperature indices show high correlations, but comparisons between the cumulative distributions at each grid box show differences in regions at high altitude or where interpolation has been performed across climatic zones. The agreement is lower between the time series from observation-based and reanalysis datasets for precipitation indices. Trends in these indices show larger spatial heterogeneity, and inter-annual variation in the global averages is often larger than the magnitude of the long-term trend. These indices show larger spatial heterogeneity in the trends, which results in comparatively small long-term trends in the global averages, which are also small compared to the inter-annual variation. Spatially these indices show on average smaller correlations than for the temperature indices, but large regions show strong positive correlations for some precipitation indices. A subset of the reanalyses has higher correlations with the latest in situ-based dataset, HadEX3, and also have smaller differences in the per-grid box cumulative distributions, indicating close agreement to the observation-based dataset. Also, we outline how the comparisons herein suggest that the gridding method used when creating HadEX3 may need to be updated for future versions of this dataset, in order to retain detail arising from topographic features, for example.

Abstract To examine the association of preoperative opioids and/or benzodiazepines on postoperative outcomes in total knee and hip arthroplasty, we retrospectively compared postoperative outcomes in those prescribed preoperative opioids and/or benzodiazepines versus those who were not who underwent elective total knee and hip arthroplasty at a single urban academic institution. Multivariable logistic regression was performed for readmission rate, respiratory failure, infection, and adverse cardiac events. Multivariable zero-truncated negative binomial regression was used for length of stay. After exclusions, there were 4307 adult patients in the study population, 2009 of whom underwent total knee arthroplasty and 2298 of whom underwent total hip arthroplasty. After adjusting for potential confounders, preoperative benzodiazepine use was associated with increased odds of readmission (p

Abstract Urban areas are often considered to be a hostile environment for wildlife as they are highly fragmented and frequently disturbed. However, these same habitats can contain abundant resources, while lacking many common competitors and predators. The urban environment can have a direct impact on the species living there but can also have indirect effects on their parasites and pathogens. To date, relatively few studies have measured how fine‐scale spatial heterogeneity within urban landscapes can affect parasite transmission and persistence. Here, we surveyed 237 greenspaces across the urban environment of Edinburgh (UK) to investigate how fine‐scale variation in socio‐economic and ecological variables can affect red fox (Vulpes vulpes) marking behavior, gastrointestinal (GI) parasite prevalence, and parasite community diversity. We found that the presence and abundance of red fox fecal markings were nonuniformly distributed across greenspaces and instead were dependent on the ecological characteristics of a site. Specifically, common foraging areas were left largely unmarked, which indicates that suitable resting and denning sites may be limiting factor in urban environments. In addition, the amount of greenspace around each site was positively correlated with overall GI parasite prevalence, species richness, and diversity, highlighting the importance of greenspace (a commonly used measure of landscape connectivity) in determining the composition of the parasite community in urban areas. Our results suggest that fine‐scale variation within urban environments can be important for understanding the ecology of infectious diseases in urban wildlife and could have wider implication for the management of urban carnivores.

Abstract Background In accordance with international guidance for tuberculosis (TB) prevention, the Tanzanian Ministry of Health recommends isoniazid preventive therapy (IPT) for children aged 12 months and older who are living with HIV. Concerns about tolerability, adherence, and potential mistreatment of undiagnosed TB with monotherapy have limited uptake of IPT globally, especially among children, in whom diagnostic confirmation is challenging. We assessed IPT implementation and adherence at a pediatric HIV clinic in Tanzania. Methods In this prospective cohort study, eligible children living with HIV aged 1–15 years receiving care at the DarDar Pediatric Program in Dar es Salaam who screened negative for TB disease were offered a 6-month regimen of daily isoniazid. Patients could choose to receive IPT via facility- or community-based care. Parents/caregivers and children provided informed consent and verbal assent respectively. Isoniazid was dispensed with the child’s antiretroviral therapy every 1–3 months. IPT adherence and treatment completion was determined by pill counts, appointment attendance, and self-report. Patients underwent TB symptom screening at every visit. Results We enrolled 66 children between July and December 2017. No patients/caregivers declined IPT. Most participants were female (n = 43, 65.1%) and the median age was 11 years (interquartile range [IQR] 8, 13). 63 (95.5%) participants chose the facility-based model; due to the small number of participants who chose the community-based model, valid comparisons between the two groups could not be made. Forty-nine participants (74.2%) completed IPT within 10 months. Among the remaining 17, 11 had IPT discontinued by their provider due to adverse drug reactions, 5 lacked documentation of completion, and 1 had unknown outcomes due to missing paperwork. Of those who completed IPT, the average monthly adherence was 98.0%. None of the participants were diagnosed with TB while taking IPT or during a median of 4 months of follow-up. Conclusions High adherence and treatment completion rates can be achieved when IPT is integrated into routine, self-selected facility-based pediatric HIV care. Improved record-keeping may yield even higher completion rates. IPT was well tolerated and no cases of TB were detected. IPT for children living with HIV is feasible and should be implemented throughout Tanzania.

Background: A case report published in 2019 described a patient who presented with difficult-to-manage atrial fibrillation (AF) that consistently was associated with alcohol consumption. After the patient did not respond to drug therapy, a novel beta-blocker (BB) pretreatment regimen initiated immediately before alcohol consumption successfully prevented AF occurrence. Objective: The purpose of this study was to test the hypothesis that a novel prophylactic BB therapy given before alcohol consumption could prevent AF in a rat model. Methods: An alcohol-induced AF model was developed in adult Sprague-Dawley rats of both sexes by administering alcohol (2 g/kg intraperitoneal [IP]) once every other day for a total of 4 times. Three groups were enrolled: alcohol (EtOH; n = 10); alcohol plus BB (metoprolol 50 mg/kg IP) pretreatment (EtOH+BB; n = 10); and control (n = 9). Cardiac function (assessed by echocardiography and left ventricular hemodynamics) and in vivo atrial electrophysiology and AF inducibility tests were performed 24 hours after the last injection. Results: All but 1 rat completed the study. Alcohol exposure did not significantly impact cardiac function and the atrial effective refractory period. However, alcohol exposure significantly increased AF inducibility [median (first and third quartile [Q1–Q3]) 0% (0%–0%) in control vs 60% (25%–100%) in the EtOH group; P

Background Effective implementation strategies might facilitate patient-centered medical home (PCMH) uptake and spread by targeting barriers to change. Evidence-based quality improvement (EBQI) is a multi-faceted implementation strategy that is based on a clinical-researcher partnership. It promotes organizational change by fostering innovation and the spread of those innovations that are successful. Previous studies demonstrated that EBQI accelerated PCMH adoption within Veterans Health Administration primary care practices, compared with standard PCMH implementation. Research to date has not documented fidelity to the EBQI implementation strategy, limiting usefulness of prior research findings. This paper develops and assesses clinical participants’ fidelity to three core EBQI elements for PCMH (EBQI-PCMH), explores the relationship between fidelity and successful QI project completion and spread (the outcome of EBQI-PCMH), and assesses the role of the clinical-researcher partnership in achieving EBQI-PCMH fidelity. Methods Nine primary care practice sites and seven across-sites, topic-focused workgroups participated (2010–2014). Core EBQI elements included leadership-frontlines priority-setting for QI, ongoing access to technical expertise, coaching, and mentoring in QI methods (through a QI collaborative), and data/evidence use to inform QI. We used explicit criteria to measure and assess EBQI-PCMH fidelity across clinical participants. We mapped fidelity to evaluation data on implementation and spread of successful QI projects/products. To assess the clinical-researcher partnership role in EBQI-PCMH, we analyzed 73 key stakeholder interviews using thematic analysis. Results Seven of 9 sites and 3 of 7 workgroups achieved high or medium fidelity to leadership-frontlines priority-setting. Fidelity was mixed for ongoing technical expertise and data/evidence use. Longer duration in EBQI-PCMH and higher fidelity to priority-setting and ongoing technical expertise appear correlated with successful QI project completion and spread. According to key stakeholders, partnership with researchers, as well as bi-directional communication between leaders and QI teams and project management/data support were critical to achieving EBQI-PCMH fidelity. Conclusions This study advances implementation theory and research by developing measures for and assessing fidelity to core EBQI elements in relationship to completion and spread of QI innovation projects or tools for addressing PCMH challenges. These results help close the gap between EBQI elements, their intended outcome, and the finding that EBQI-PCMH resulted in accelerated adoption of PCMH.

BackgroundRoad traffic injury is a pressing public health issue in Tanzania. Increasing helmet use among motorcycle drivers can help reduce the burden due to road traffic injuries in the country. Helmet adherence can be supported through mobile health interventions. ObjectiveThe aim of this study is to evaluate the comparative impact of two different types of SMS text messaging reminders on motorcycle helmet use. MethodsParticipants were 391 commercial motorcycle taxi drivers in Dar es Salaam, Tanzania. Participants were randomized into three groups, each receiving a different set of messages: (1) social norming messages aimed at emphasizing society’s positive stance on helmet wearing, (2) fear appeal messages that emphasized the dangers of riding without a helmet, and (3) control group messages, which included basic road safety messages unrelated to helmet use. Every participant received the control messages. Adherence to helmet use was evaluated by self-report through surveys conducted at baseline, 3 weeks, and 6 weeks. ResultsAt 6 weeks, the odds of self-reporting consistent helmet use were estimated to be 1.58 times higher in the social norming group than in the control group (P=.04), though this difference was not significant after accounting for multiple testing. There was little difference between fear appeal and control group recipients (odds ratio 1.03, P=.47). Subgroup analysis suggests that both fear appeal and social norming message types might have been associated with increased helmet use among participants who did not consistently wear helmets at baseline (odds ratio 1.66 and odds ratio 1.84, respectively), but this was not significant (P=.11 and P=.07, respectively). Among those who were consistent wearers at baseline, the social norming messages performed better than the fear appeal messages, and this difference reached traditional significance (P=.03), but was not significant after accounting for multiple testing. ConclusionsThe use of SMS text messaging reminders may improve helmet use among motorcycle drivers when framed as social norming messages. Given that nearly half of the drivers in our sample did not consistently wear their helmets on every trip, strategies to increase consistent usage could greatly benefit public safety. Trial RegistrationClinicalTrials.gov NCT02120742; https://clinicaltrials.gov/ct2/show/NCT02120742

Allogeneic hematopoietic stem cell transplantation (HSCT) is an established curative treatment that has significantly improved clinical outcome of pediatric patients with malignant and non-malignant disorders. This is partly because of the use of safer and more effective combinations of chemo- and serotherapy prior to HSCT. Still, complications due to the toxicity of these conditioning regimens remains a major cause of transplant-related mortality (TRM). One of the most difficult challenges to further improve HSCT outcome is reducing toxicity while maintaining efficacy. The use of personalized dosing of the various components of the conditioning regimen by means of therapeutic drug monitoring (TDM) has been the topic of interest in the last decade. TDM could play an important role, especially in children who tend to show greater pharmacokinetic variability. However, TDM should only be performed when it has clear added value to improve clinical outcome or reduce toxicity. In this review, we provide an overview of the available evidence for the relationship between pharmacokinetic parameters and clinical outcome or toxicities of the most commonly used conditioning agents in pediatric HSCT.

Fat contributes most of the energy for migratory flight of birds, whereas lean body tissues (muscles and organs) contribute amino acids and water to maintain metabolic and osmotic homeostasis. During refueling at stopover sites, both fat and lean mass are recovered, but the dynamics of this recovery are poorly understood. We used non-invasive quantitative magnetic resonance (QMR) analysis to measure fat and lean mass of > 3,500 individuals of 25 songbird species during six spring and three autumn migration seasons between 2009 and 2019 at Long Point, ON, Canada. We used allometric scaling analysis and linear mixed-effects modeling of body composition data at both the population level (single capture) and the individual level (recapture). In the population-level analysis, lean mass scaled hypoallometrically with body mass, such that for every 20% increase in body mass, lean mass was predicted to increase by 12.1% in spring and 12.8% in autumn. Fat scaled hyperallometrically with body mass, such that for every 20% increase in body mass, fat mass was predicted to increase by 144% in spring and 136% in autumn. At the individual level, these allometric relationships were more extreme. As a result of this differential allometry, at low body masses, lean and fat mass contributes nearly equally to changes in mass, but at high body mass fat deposition becomes progressively more dominant. Spring migrants deposited relatively more fat than autumn migrants, and in autumn juvenile birds tended to have greater lean mass than adults. Our findings show that lean mass deposition during refueling by songbirds is substantial, and in line with the losses of protein expected in flight. The process of fat and lean mass deposition is characterized by non-linear dynamics which are influenced by the current body composition, season, and, to a lesser extent, age. The patterns suggest that the need for dietary protein to rebuild lean mass will be greater when body mass is low, during autumn migration, and in juvenile birds.

Over the last 60 years, Arctic goose populations have increased while many sympatric tundra nesting bird populations have declined. Hyperabundant geese have well-documented effects on tundra habitats, which can alter habitat use by sympatric bird species. These habitat changes may also alter invertebrate communities and abundances, with potentially important, but as of yet, undocumented effects on insectivorous birds such as shorebirds. Here, we determined the effects of goose-induced habitat alteration on invertebrate communities and relate the observed changes to shorebird diet. At sites and habitat types representing a gradient of goose influence, we identified goose-related changes in ground cover and linked these factors to variation in invertebrate communities. We then used DNA metabarcoding to characterize the diet of six shorebird species across sites and identify inter-site variation in abundance, biomass, and timing of emergence of dominant shorebird prey items. Invertebrate diversity and richness did not vary either among sites or habitat types. However, for prey items identified as part of the shorebird diet, we found significantly higher abundances and biomasses at a moderately goose-influenced site than at either low or high goose-influenced sites. Biomass of Tipulidae, the dominant prey taxon for shorebirds at the study sites, was 7.5 times higher at the moderately goose-influenced site compared to the site where goose influence was minor. We attribute this enhancement of prey biomass to both the fertilizing effect of goose fecal pellets and the moderate grazing pressure. Many studies have documented adverse effects of overabundant geese, but here we show that a moderate degree of goose grazing can lead to enhanced biomass of invertebrates, with the potential for improved shorebird foraging success and chick growth. These benefits, however, might be outweighed by negative effects of goose-induced habitat alteration and predation pressure.

Mass vaccination initiatives are underway worldwide, and a considerable percentage of the world’s population is now vaccinated. This study examined the association of COVID-19 deaths per 1000 cases with a fully vaccinated population. The global median deaths per 1000 cases were 15.68 (IQR 9.84, 25.87) after 6 months of vaccinations and 11.96 (IQR 6.08, 20.63) after 12 months. Across 164 countries, we found significant variations in vaccination levels of populations, booster doses, and mortality, with higher vaccine coverage and lower mortality in high-income countries. Several regression models were performed to test the association between vaccination and COVID-19 mortality. Control variables were used to account for confounding variables. A 10-percentage-point increase in vaccination was associated with an 18.1% decrease in mortality after 6 months (95%CI, 7.4–28.8%) and a 16.8% decrease after 12 months (95%CI, 6.9–26.7%). A 10-percentage-point increase in booster vaccination rates was associated with a 33.1% decrease in COVID-19 mortality (95%CI, 16.0–50.2%). This relationship is present in most analyses by country income groups with variations in the effect size. Efforts are needed to reduce vaccine hesitancy while ensuring suitable infrastructure and supply to enable all countries to increase their vaccination rates.

Impacts from marine heatwaves can be devastating, but understanding their causes is largely based on case studies. Here the authors carry out a global assessment of literature and sea surface temperatures to identify important local processes, climate modes and teleconnections that drive marine heatwaves regionally.

Abstract Background Despite the known benefits of early, specialized intervention for toddlers with Autism Spectrum Disorder (ASD), access to such intervention remains limited. This pragmatic trial examines a novel healthcare delivery model (Screen-Refer-Treat [SRT]), which capitalizes upon existing health care and early intervention (EI) infrastructure to increase community capacity for ASD detection and treatment before age 3, when it is likely to have the greatest impact. This model comprises three components: (1) universal use of Stage 1 ASD screening by primary care providers (PCPs) at 18-month well-child visits (i.e., Screen); (2) immediate referral of positive screens to a community-based EI program (i.e., Refer); and (3) provision of an inexpensive, evidence-based ASD-specialized treatment by EI providers, after verifying ASD risk with a Stage 2 screen (i.e., Treat). This paper describes our research design and the initial successes, challenges, and adaptations made during the early implementation phase. Method/design A stepped-wedge cluster RCT was used to implement the SRT model sequentially in four diverse Washington State counties (“clusters”). Counties are randomly assigned to the time of receipt of the SRT intervention, which comprises training workshops and technical assistance focused on the use of evidence-based ASD screening and intervention tools. Separate cohorts of families with toddlers (16–35 months old) with and without ASD concerns are recruited before and after the SRT intervention from participating PCP practices and EI programs. PCPs and EI providers complete measures on their screening, referral, and intervention practices before and after the SRT intervention. Each family cohort completes surveys about their well-being, parenting efficacy, health care satisfaction, and toddler’s social-communicative behaviors. Conclusion This trial is the first of its kind to work simultaneously with two service delivery systems with the goal of improving early detection and treatment for ASD. Our approach was successful in attaining buy-in from PCPs and EI providers, building and maintaining partnerships with providers, and achieving high levels of retention and survey completion. Fostering provider engagement and problem-solving issues together as partners were integral to overcoming the main challenges. Numerous lessons have been learned thus far, which have applicability for implementation researchers in ASD and those in other fields. Trial registration The registration number for this trial is NCT02409303 and it was posted on ClinicalTrials.gov on April 6, 2015.

Abstract Background Performing well-powered randomised controlled trials (RCTs) of new treatments for rare diseases is often infeasible. However, with the increasing availability of historical data, incorporating existing information into trials with small sample sizes is appealing in order to increase the power. Bayesian approaches enable one to incorporate historical data into a trial’s analysis through a prior distribution. Methods Motivated by a RCT intended to evaluate the impact on event-free survival of mifamurtide in patients with osteosarcoma, we performed a simulation study to evaluate the impact on trial operating characteristics of incorporating historical individual control data and aggregate treatment effect estimates. We used power priors derived from historical individual control data for baseline parameters of Weibull and piecewise exponential models, while we used a mixture prior to summarise aggregate information obtained on the relative treatment effect. The impact of prior-data conflicts, both with respect to the parameters and survival models, was evaluated for a set of pre-specified weights assigned to the historical information in the prior distributions. Results The operating characteristics varied according to the weights assigned to each source of historical information, the variance of the informative and vague component of the mixture prior and the level of commensurability between the historical and new data. When historical and new controls follow different survival distributions, we did not observe any advantage of choosing a piecewise exponential model compared to a Weibull model for the new trial analysis. However, we think that it remains appealing given the uncertainty that will often surround the shape of the survival distribution of the new data. Conclusion In the setting of Sarcome-13 trial, and other similar studies in rare diseases, the gains in power and accuracy made possible by incorporating different types of historical information commensurate with the new trial data have to be balanced against the risk of biased estimates and a possible loss in power if data are not commensurate. The weights allocated to the historical data have to be carefully chosen based on this trade-off. Further simulation studies investigating methods for incorporating historical data are required to generalise the findings.

(1) Background: There is a dearth of data on the levels and determinants of testing for drug-related infectious diseases among people who use drugs (PWUD). We assessed the proportions and determinants of testing for drug-related infectious diseases to inform ongoing interventions for PWUD. (2) Methods: A cross-sectional study involving 599 PWUD was conducted in Dar es Salaam and Tanga between January and February 2019. Data were collected through a researcher-administered questionnaire using handheld tablets. Logistic regression models were used to identify independent testing determinants for drug-related infectious diseases. (3) Results: A majority (98.0%) of participants were males, with a mean age of 36.8 (SD = 7.8) years. 75.0%, 40.6%, 38.6%, and 8.2% reported having ever tested for HIV, tuberculosis (TB), sexually transmitted infections (STIs), and viral hepatitis, respectively. The likelihood of HIV testing was higher among those living with someone (AOR = 2.18, 95% CI: 1.09–4.68) compared with those who were homeless and perceived treatment was appropriate (AOR = 2.18, 95% CI: 1.05–4.46), but was lower among those who experienced mild to moderate (AOR = 0.44, 95% CI: 0.21–0.95) and severe internalized stigma (AOR = 0.44, 95% CI: 0.22–0.94) compared with those reporting no internalized stigma, and among those who experienced financial difficulties resulting from spending on health care services (AOR = 0.60, 95% CI: 0.40–0.89). Perception of treatment appropriateness (AOR = 2.29, 96% CI: 1.10–5.06) and severe enacted stigma (AOR = 1.90, 95% CI: 1.06–3.42) were associated with increased odds of TB testing. The odds of STIs testing increased among those who were married (AOR = 2.31, 95% CI: 1.45–3.72) compared with those who were single and those who had experienced mild (AOR = 2.39, 95% CI: 1.28–4.53) or severe (AOR = 6.20, 95% CI: 1.99–23.83) sexual violence, compared with those who had not experienced sexual violence. However, the odds decreased among those who had been remanded in the past month (AOR = 0.64, 95% CI: 0.43–0.95) compared with those who were not remanded and among those who had financial difficulties resulting from spending on health care services (AOR = 0.66, 95% CI: 0.47–0.94). The likelihood of testing for viral hepatitis testing increased among those who had heard about the comprehensive HIV intervention package (CHIP) (AOR = 2.59, 95% CI: 1.40–4.94); however, it decreased among those who had financial difficulties resulting from spending on health care services (AOR = 0.48, 95% CI: 0.24–0.92). (4) Conclusions: Except for HIV, PWUD had undergone limited testing for drug-related infectious diseases. The study findings highlight some factors influencing testing for the selected infectious diseases investigated, which should be targeted for tailored interventions to improve diagnosis and treatment.

Background: The term ‘last mile’ has been used across disciplines to refer to populations who are farthest away, most difficult to reach, or last to benefit from a program or service. However, last mile research lacks a shared understanding around its conceptualization. Objectives: This project used a concept mapping process to answer the questions: what is last mile research in global health and, how can it be used to make positive change for health equity in the last mile? Methods: Between July and December 2019, a five-stage concept mapping exercise was undertaken using online concept mapping software and an in-person consensus meeting. The stages were: establishment of an expert group and focus prompt; idea generation; sorting and rating; initial analysis and final consensus meeting. Results: A group of 15 health researchers with experience working with populations in last mile contexts and who were based at the Matariki Network institutions of Queen’s University, CAN and Dartmouth College, USA took part. The resulting concept map had 64 unique idea statements and the process resulted in a map with five clusters. These included: (1) Last mile populations; (2) Research methods and approaches; (3) Structural and systemic factors; (4) Health system factors, and (5) Broader environmental factors. Central to the map were the ideas of equity, human rights, health systems, and contextual sensitivity. Conclusion: This is the first time ‘last mile research’ has been the focus of a formal concept mapping exercise. The resulting map showed consensus about who last mile populations are, how research should be undertaken in the last mile and why last mile health disparities exist. The map can be used to inform research training programs, however, repeating this process with researchers and members from different last mile populations would also add further insight.

Goal contagion is a social-cognitive approach to understanding how other people’s behavior influences one’s goal pursuit: An observation of goal-directed behavior leads to an automatic inference and activation of the goal before it can be adopted and pursued thereafter by the observer. We conducted a meta-analysis focusing on experimental studies with a goal condition, depicting goal-directed behavior and a control condition. We searched four databases (PsychInfo, Web of Science, ScienceDirect, and JSTOR) and the citing literature on Google Scholar, and eventually included e = 48 effects from published studies, unpublished studies and registered reports based on 4751 participants. The meta-analytic summary effect was small − 'g' = 0.30, '95%CI' [0.21; 0.40], τ² = 0.05, '95%CI' [0.03, 0.13] − implying that goal contagion might occur for some people, compared to when this goal is not perceived in behavior. However, the original effect seemed to be biased through the current publication system. As shown by several publication-bias tests, the effect could rather be half the size, for example, selection model: 'g' = 0.15, '95%CI' [–0.02; 0.32]. Further, we could not detect any potential moderator (such as the presentation of the manipulation and the contrast of the control condition). We suggest that future research on goal contagion makes use of open science practices to advance research in this domain.