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Abstract Small‐cell lung cancer (SCLC) is the most lethal type of lung cancer. Specifically, MYC‐driven non‐neuroendocrine SCLC is particularly resistant to standard therapies. Lurbinectedin was recently approved for the treatment of relapsed SCLC, but combinatorial approaches are needed to increase the depth and duration of responses to lurbinectedin. Using high‐throughput screens, we found inhibitors of ataxia telangiectasia mutated and rad3 related (ATR) as the most effective agents for augmenting lurbinectedin efficacy. First‐in‐class ATR inhibitor berzosertib synergized with lurbinectedin in multiple SCLC cell lines, organoid, and in vivo models. Mechanistically, ATR inhibition abrogated S‐phase arrest induced by lurbinectedin and forced cell cycle progression causing mitotic catastrophe and cell death. High CDKN1A/p21 expression was associated with decreased synergy due to G1 arrest, while increased levels of ERCC5/XPG were predictive of increased combination efficacy. Importantly, MYC‐driven non‐neuroendocrine tumors which are resistant to first‐line therapies show reduced CDKN1A/p21 expression and increased ERCC5/XPG indicating they are primed for response to lurbinectedin–berzosertib combination. The combination is being assessed in a clinical trial NCT04802174.

Student-created videos engage students' interests, creativity, and content knowledge and enrich collaborative learning in STEM education. These videos enhance critical thinking and analytical skills, which are essential tools in the fields of science, technology, engineering, and mathematics (STEM). This study presents the results of such an assignment across several STEM areas (biology, chemistry, exercise science, information technology, and mathematics) at a minority-serving, liberal arts higher education institution in the southeast region of the United States. Undergraduate students (n = 557) across varied, online course modalities (synchronous and asynchronous) were required to create four problem-solving videos 3–8 min in duration. Assessment tools included a self-assessment of learning gains survey given to control and experimental groups and a post-video creation survey given only to experimental groups. Grade data was also collected from all sections. Comparing the experimental and control groups, students showed a statistically significant gain in their ability to give oral presentations, create videos, and edit videos. Qualitative data from free-response questions corroborate these gains and suggest that students also grew in content knowledge and conceptual understanding through these assignments. Our study implements a multimedia theoretical framework which suggests students learn more effectively from consuming presentations with both auditory and visual components. Our results suggest students see similar gains from producing presentations with both auditory and visual components. Further our results suggest that multimedia production enhances students' presentation skills. From a practical perspective, this study suggests that faculty should incorporate student-created videos in online classes, which typically require oral presentations in person. Faculty are also advised to require oral and visual components within these videos to maximize learning gains from the perspective of a multimedia theoretical framework. [ABSTRACT FROM AUTHOR]

Mass extinctions are considered to be quintessential examples of Court Jester drivers of macroevolution, whereby abiotic pressures drive a suite of extinctions leading to huge ecosystem changes across geological timescales. Most research on mass extinctions ignores species interactions and community structure, limiting inference about which and why species go extinct, and how Red Queen processes that link speciation to extinction rates affect the subsequent recovery of biodiversity, structure and function. Here, we apply network reconstruction, secondary extinction modelling and community structure analysis to the Early Toarcian (Lower Jurassic; 183 Ma) Extinction Event and recovery. We find that primary extinctions targeted towards infaunal guilds, which caused secondary extinction cascades to higher trophic levels, reproduce the empirical post-extinction community most accurately. We find that the extinction event caused a switch from a diverse community with high levels of functional redundancy to a less diverse, more densely connected community of generalists. Recovery was characterised by a return to pre-extinction levels of some elements of community structure and function prior to the recovery of biodiversity. Full ecosystem recovery took ~7 million years at which point we see evidence of dramatically increased vertical structure linked to the Mesozoic Marine Revolution and modern marine ecosystem structure. Mass extinctions have repeatedly restructured communities through geological time, but biotic interactions are rarely considered in investigations of extinction dynamics and ecosystem recovery. Here the authors present evidence that secondary extinction cascades were important during a Jurassic hyperthermal extinction event and that it took over 7 million years for community structure to fully recover. [ABSTRACT FROM AUTHOR]

We study the transport properties of underdoped trilayer cuprate HgBa2Ca2Cu3O8+δ with doping level p = 0.10–0.12 in magnetic field up to 88 T. We report for the first time in a cuprate superconductor a dramatic change of the quantum oscillation spectrum versus temperature, which is accompanied by a sign change of the Hall effect below T ≈10 K. Based on numerical simulations, we infer a Fermi surface reconstruction in the inner plane from an antiferromagnetic state (hole pockets) to a biaxial charge density wave state (electron pockets). We show that both orders compete and share the same hotspots of the Fermi surface, and we discuss our result in the context of spin-fermion models. [ABSTRACT FROM AUTHOR]

We developed a covalent antithrombin-heparin complex (ATH) with superior In vivo anticoagulant efficacy compared to non-covalent antithrombin (AT) + unfractionated heparin (H). Previous in vitro studies of ATH, investigating the mechanisms behind its efficacy, were done in the absence of endothelium. Since the endothelial surface modulates hemostasis, we investigated its impact on the in vitro anticoagulant properties of ATH and AT+H. Discontinuous second order rate constant enzyme inhibition assays, fibrin formation, and plasma clot generation were performed in the presence of ATH or AT+H, with and without endothelium present. ATH had an increased rate of direct inhibition of IIa and Xa, and increased inhibition of IIa-induced fibrin formation, compared to AT+H. When compared at equal anti-Xa levels, ATH was less effective than AT+H at catalyzing inhibition of plasma clot generation. These results were found in both the presence and absence of endothelium. Endothelium decreased the rate of IIa inhibition, and reduced clot time in IIa-induced fibrin formation and plasma clot generation assays, for both ATH and AT+H. Endothelium did not impact the activity of ATH differently to AT+H. This supports the growing body of evidence suggesting ATH may be a beneficial anticoagulant for potential clinical use. [ABSTRACT FROM AUTHOR]

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Politics and science are inextricably connected, particularly in relation to the climate emergency and other environmental crises, yet science education is an often overlooked site for engaging with the political dimensions of environmental issues. This study examines how science teachers in England experience politics—specifically political participation—in relation to the environment in school science, against a background of increased obstruction in civic space. The study draws on an analysis of theoretically informed in-depth interviews with eleven science teachers about their experiences of political participation in relation to environmental issues. We find that politics enters the science classroom primarily through informal conversations initiated by students rather than planned by teachers. When planned for, the emphasis is on individual, latent–political (civic) engagement rather than manifest political participation. We argue that this is a symptom of the post-political condition and call for a more enabling environment for discussing the strengths and limitations of different forms of political participation in school science. [ABSTRACT FROM AUTHOR]

Recent observations of Jupiter's atmosphere showing unexpected depletion of ammonia below the ammonia cloud-forming region has brought up the question of whether a single point measurement below the cloud decks in a giant planet atmosphere can provide sufficient information to answer fundamental science questions. We outline here the science questions that can only be answered by in situ observations in the giant planet atmospheres, many of which are location invariant. These questions are identified in the recent planetary science decadal survey as high priority for answering over the next decade. We evaluate the implications of the ammonia observations at Jupiter for the specific measurements needed and demonstrate that they do not invalidate single point measurements made to answer these questions. [ABSTRACT FROM AUTHOR]

The tumour suppressor p16/CDKN2A and the metabolic gene, methyl-thio-adenosine phosphorylase (MTAP), are frequently co-deleted in some of the most aggressive and currently untreatable cancers. Cells with MTAP deletion are vulnerable to inhibition of the metabolic enzyme, methionine-adenosyl transferase 2A (MAT2A), and the protein arginine methyl transferase (PRMT5). This synthetic lethality has paved the way for the rapid development of drugs targeting the MAT2A/PRMT5 axis. MAT2A and its liver- and pancreas-specific isoform, MAT1A, generate the universal methyl donor S-adenosylmethionine (SAM) from ATP and methionine. Given the pleiotropic role SAM plays in methylation of diverse substrates, characterising the extent of SAM depletion and downstream perturbations following MAT2A/MAT1A inhibition (MATi) is critical for safety assessment. We have assessed in vivo target engagement and the resultant systemic phenotype using multi-omic tools to characterise response to a MAT2A inhibitor (AZ'9567). We observed significant SAM depletion and extensive methionine accumulation in the plasma, liver, brain and heart of treated rats, providing the first assessment of both global SAM depletion and evidence of hepatic MAT1A target engagement. An integrative analysis of multi-omic data from liver tissue identified broad perturbations in pathways covering one-carbon metabolism, trans-sulfuration and lipid metabolism. We infer that these pathway-wide perturbations represent adaptive responses to SAM depletion and confer a risk of oxidative stress, hepatic steatosis and an associated disturbance in plasma and cellular lipid homeostasis. The alterations also explain the dramatic increase in plasma and tissue methionine, which could be used as a safety and PD biomarker going forward to the clinic. [ABSTRACT FROM AUTHOR]

Background: Vitamin D (25OHD) can modulate pathways and mechanisms that regulate blood pressure (BP). Observational studies in children and adults have shown an inverse association between 25OHD and BP. Studies evaluating associations between 25OHD and BP in pediatric chronic kidney disease are limited. Methods: We evaluated the associations between 25OHD and BP using data from the Chronic Kidney Disease in Children (CKiD) study. Clinic or ambulatory BP index was defined as participant's BP divided by 95th age-sex-height-specific BP percentile, an index > 1 suggests hypertension. Primary outcomes of interest were changes in systolic and diastolic clinic and ambulatory BP indices over follow-up. Linear mixed-effects models were used to evaluate associations between BP indices and 25OHD. Results: The study cohort consisted of 370 participants who contributed 970 person-visits. A subset of 194 participants with ambulatory BP data contributed 465 person-visits. There was an association between baseline 25OHD levels and clinic systolic BP index such that for every 10 ng/ml lower 25OHD, clinic systolic BP index was 1.0% higher (95%CI: 0.2–1.8, p = 0.016) between participants. The association between clinic diastolic BP index with baseline 25OHD was not significant. For within-person changes, longitudinal decreases in 25OHD were not significantly associated with concomitant increases in clinic systolic or diastolic BP index. There were no significant associations between 25OHD levels at baseline or longitudinally with 24-h ABPM indices. Conclusions: Low 25OHD levels were associated with higher clinic systolic BP in children with CKD. Vitamin D supplementation to maintain normal 25OHD levels might be a useful adjunctive treatment in optimizing BP control in these high-risk patients. [ABSTRACT FROM AUTHOR]

Abstract Year 2020 will mark History, with the emergence of the new Covid-19 virus, and more importantly, the consequent political decisions to apply freedom restriction at such a large-scale. Identifying the human behaviours during this extraordinary period represents a unique opportunity to both improve our fundamental knowledge and to improve future management of similar issues. Throughout almost all the duration of the French lockdown (from March 24, 2020 to May 10, 2020), we carried out an online survey on more than 12,000 individuals well distributed over the country. This online survey was performed by using both LimeSurvey and Google Forms services and was addressed to adults living in France. Statistical analyses combined classical inferential approach, mapping, clustering and text mining. The results showed that a significant part of the population moved out just before the lockdown (around 10% of our sample) and we highlighted three different profiles of participants. The results emphasised that the lockdown measures compliance was lower in two cases: (i) an unfavourable living environment (referring to social and economic inequity) associated with a high feeling of fear and a lack of trust towards Governmental measures; or (ii) the feeling that the risk was low due to the fact that others complied with the measures. In case a similar situation should occur again, it is recommended that Governments broadcast clear speeches to improve trust, limit fear and increase cooperative behaviours.

Background: Crohn's disease (CD) significantly affects patients' health-related quality of life and well-being. Aims: Communicating Needs and Features of IBD Experiences (CONFIDE) survey explores the experience and impact of moderate-to-severe CD symptoms on patients' lives and identifies communication gaps between patients and health care professionals (HCPs). Methods: Online, quantitative, cross-sectional surveys of patients, and HCPs were conducted in the United States (US), Europe (France, Germany, Italy, Spain, United Kingdom), and Japan. Criteria based on previous treatment, steroid use, and/or hospitalization defined moderate-to-severe CD. US and Europe data are presented as descriptive statistics. Results: Surveys were completed by 215 US and 547 European patients and 200 US and 503 European HCPs. In both patient groups, top three symptoms currently (past month) experienced were diarrhea, bowel urgency, and increased stool frequency, with more than one-third patients wearing diaper/pad/protection at least once a week in past 3 months due to fear of bowel urgency-related accidents. HCPs ranked diarrhea, blood in stool, and increased stool frequency as the most common symptoms. Although 34.0% US and 27.2% European HCPs ranked bowel urgency among the top five symptoms affecting patient lives, only 12.0% US and 10.9% European HCPs ranked it among top three most impactful symptoms on treatment decisions. Conclusion: Bowel urgency is common and impactful among patients with CD in the US and Europe. Differences in patient and HCP perceptions of experiences and impacts of bowel urgency exist, with HCPs underestimating its burden. Proactive communication between HCPs and patients in clinical settings is crucial for improving health outcomes in patients with CD. [ABSTRACT FROM AUTHOR]

Background: The Insomnia Severity Index (ISI) is a widely used measure of insomnia severity. Various ISI research findings suggest different factor solutions and meaningful within-individual change (MWIC) to detect treatment response in patients with insomnia. This study examined an ISI factor solution and psychometric indices to define MWIC in a robust patient sample from clinical trial settings. Methods: We endeavored to improve upon previous validation of ISI by examining structural components of confirmatory factor analysis (CFA) models using two large, placebo-controlled clinical trials of lemborexant for insomnia. Using the best-fitting two-factor solution, we evaluated anchor-based, distribution-based and receiver operating characteristic (ROC) curve methods to derive an estimate of the MWIC. Results: The model structure for the 7-item scale proposed in other research did not fit the observed data from our two lemborexant clinical trials (N = 1956) as well as a two-factor solution based on 6 items did. Using triangulation of anchor-based, distribution-based, and ROC methods, we determined that a 5-point reduction using 6 items best represented a clinically meaningful improvement in individuals with insomnia in our patient sample. Conclusions: A 6-item two-factor scale had better psychometric properties than the 7-item scale in this patient sample. On the 6-item scale, a reduction of 5 points in the ISI total score represented the MWIC. Generalizability of the proposed MWIC may be limited to patient populations with similar demographic and clinical characteristics. [ABSTRACT FROM AUTHOR]

Background: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. Methods: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. Results: 132 pts were included. Median age was 56 years (28–91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5–6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. Conclusion: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience. [ABSTRACT FROM AUTHOR]

Background: Cognitive impairment associated with schizophrenia (CIAS) represents a distinct, persistent, and core group of schizophrenia symptoms. Cognitive symptoms have been shown to have an impact on quality of life. There are several published CIAS measures, but none based on direct patient self-report. It is important to capture the patient's perspective to supplement performancebased outcome measures of cognition to provide a complete picture of the patient's experience. This paper describes additional validation work on the Patient-Reported Experience of Cognitive Impairment in Schizophrenia (PRECIS) instrument. Methods: Data from two large, international, pharmaceutical clinical trials in medically and psychiatrically stable English-speaking patients with schizophrenia and 88 healthy controls were analyzed. An exploratory factor analysis (EFA) was conducted in one trial (n = 215), using the original 35-item PRECIS. The factor structure suggested by EFA was further evaluated using item response theory (IRT; Samejima's graded response model), and tested using confirmatory factor analysis (CFA). Both EFA and CFA results were tested in a second trial with similar inclusion/exclusion characteristics (n = 410). Additional statistical properties were evaluated in healthy controls. Results: EFA suggested that the best solution after item reduction suggested a factor structure of 6 factors based on 26 items (memory, communication, self-control, executive function, attention, sharpness of thought), supporting a total score, with an additional 2-item bother score (28 items in all). IRT analysis indicated the items were well-ordered within each domain. The CFA demonstrated excellent model fit, accounting for 69% of the variance. The statistical properties of the 28-item version of the PRECIS were confirmed in the second trial. Evidence for internal consistency and test-retest reliability was robust. Known-groups validity was supported by comparison of healthy controls with patients with schizophrenia. Correlations indicated moderate associations between PRECIS and functioning instruments like the Schizophrenia Cognition Rating Scale (SCoRS), but weak correlations with performance-based outcomes like MATRICS Consensus Cognitive Battery (MCCB). Discussion: Using two clinical trial samples, we identified a robust factor structure for the PRECIS and were able to replicate it in the second sample. Evaluation of the meaningful score difference (MSD) should be repeated in future studies, as these samples did not show enough change for it to be evaluated. Conclusions: This analysis provides strong evidence for the reliability and validity of the PRECIS, a 28-item, patient-reported instrument to assess cognitive impairment associated with schizophrenia. The correlation with functioning and the weak correlation with performance on cognitive tasks suggests that patient reports of cognitive impairment measure a unique aspect of patient experience. [ABSTRACT FROM AUTHOR]

Curcumin, an important bioactive compound and natural photosensitizer, which exhibits various biological properties, was loaded into inorganic carriers MgAl/ZnAl layered double hydroxides (LDH). The supporting matrices were obtained by co-precipitation, and a surfactant was used for including the organic drug. The structural, morphological, and spectral properties of the obtained composites were followed by X-ray diffraction, FTIR, SEM, UV–Vis, and fluorescence spectroscopy in solid state and in different solvents. The prepared formulations, the curcumin-loaded carriers, were introduced in alcohol-aqueous mixtures and the effect of solvent on the spectral properties of the formulations was investigated. Interactions between the keto-enol group of the pigment and the metals in LDHs laminates as well as inter-molecular bonds between alcohols and curcumin were evidenced. As a consequence, it was concluded that the composition of the carrier as well as the nature of the solvent determine the structural changes of the formulations. MgAl-LDH in powder has better spectral characteristics in the low-energy range (UV–Vis and fluorescence) than ZnAl-LDH. Their spectra are altered when methanol and water are present in the solvent mixture. The released curcumin concentration is in the range for photosensitization applications. The results have potential utilizations in many fields such as food, pharmaceutical, and biology. [ABSTRACT FROM AUTHOR]

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear. Loss of inner ear hair cells leads to permanent hearing loss and balance dysfunction. Whether human utricular cells regenerate is unknown. Here, the authors present a single-cell resource of utricular cells from organ donors and schwannoma patients and describe transcriptional changes during homeostasis and in response to damage. [ABSTRACT FROM AUTHOR]

This theme-based book review considers four recent titles related to governments? role in development and public finance: Sustainable Urban Futures in Africa, edited by Patrick Brandful Cobbinah and Michael Addaney; Research Handbook on Public Financial Management, edited by Komla D. Dzigbede and W. Bartley Hildreth; Decisions, Preferences, and Heuristics: An Introduction to Economic Psychology and Behavioral Economics, by Pere Mir-Artigues; and China?s Economic Development: Implications for the World, by Cai Fang. [ABSTRACT FROM AUTHOR]

The exploration of carbon-to-oxygen ratios has yielded intriguing insights into the composition of close-in giant exoplanets, giving rise to a distinct classification: carbon-rich planets, characterized by a carbon–to–oxygen ratio ≥ 1 in their atmospheres, as opposed to giant planets exhibiting carbon–to–oxygen ratios close to the protosolar value. In contrast, despite numerous space missions dispatched to the outer solar system and the proximity of Jupiter, Saturn, Uranus, and Neptune, our understanding of the carbon-to-oxygen ratio in these giants remains notably deficient. Determining this ratio is crucial as it serves as a marker linking a planet’s volatile composition directly to its formation region within the disk. This article provides an overview of the current understanding of the carbon-to-oxygen ratio in the four gas giants of our solar system and explores why there is yet no definitive dismissal of the possibility that Jupiter, Saturn, Uranus, or Neptune could be considered carbon-rich planets. Additionally, we delve into the three primary formation scenarios proposed in existing literature to account for a bulk carbon-to-oxygen ratio ≥ 1 in a giant planet. A significant challenge lies in accurately inferring the bulk carbon-to-oxygen ratio of our solar system’s gas giants. Retrieval methods involve integrating in situ measurements from entry probes equipped with mass spectrometers and remote sensing observations conducted at microwave wavelengths by orbiters. However, these methods fall short of fully discerning the deep carbon-to-oxygen abundance in the gas giants due to their limited probing depth, typically within the 10–100 bar range. To complement these direct measurements, indirect determinations rely on understanding the vertical distribution of atmospheric carbon monoxide in conjunction with thermochemical models. These models aid in evaluating the deep oxygen abundance in the gas giants, providing valuable insights into their overall composition. [ABSTRACT FROM AUTHOR]

Paediatric imaging protocols should be carefully optimised to maintain the desired image quality while minimising the delivered patient dose. A paediatric chest phantom was designed, constructed and evaluated to optimise chest CT examinations for infants. The phantom was designed to enable dosimetry and image quality measurements within the anthropomorphic structure. It was constructed using tissue equivalent materials to mimic thoracic structures of infants, aged 0–6 months. The phantom materials were validated across a range of diagnostic tube voltages with resulting CT numbers found equivalent to paediatric tissues observed via a survey of clinical paediatric chest studies. The phantom has been successfully used to measure radiation dose and evaluate various image quality parameters for paediatric specific protocols. [ABSTRACT FROM AUTHOR]

Music is a universal yet diverse cultural trait transmitted between generations. The extent to which global musical diversity traces cultural and demographic history, however, is unresolved. Using a global musical dataset of 5242 songs from 719 societies, we identify five axes of musical diversity and show that music contains geographical and historical structures analogous to linguistic and genetic diversity. After creating a matched dataset of musical, genetic, and linguistic data spanning 121 societies containing 981 songs, 1296 individual genetic profiles, and 121 languages, we show that global musical similarities are only weakly and inconsistently related to linguistic or genetic histories, with some regional exceptions such as within Southeast Asia and sub-Saharan Africa. Our results suggest that global musical traditions are largely distinct from some non-musical aspects of human history. Human groups preserve cultural history in songs passed between generations. Here the authors show that musical histories are largely independent of the history preserved in genes and languages. [ABSTRACT FROM AUTHOR]

Intersectionality and positionality can be used to examine how various aspects of identity are analyzed in the context of learners' lived experiences. When examining how learners are recognized for their skills and competencies, there are several ways in which education and credentials can be leveraged. Autoethnographies were used to examine the lived experience of how the authors used micro-credentials and digital badges to verify skills that were unrecognized in traditional contexts. Lessons from these lived experiences will be derived from a co-reflection process. Further, these lessons will be used to provide suggestions for how learning ecologies can be designed to support historically and systematically excluded learners with ways to have their skills recognized and verified. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease of 2019 (COVID-19) has disproportionately affected adults with kidney disease. Data regarding outcomes among children with kidney disease are limited. The North American Pediatric Renal Trials Collaborative Studies Registry (NAPRTCS) has followed children with chronic kidney disease (CKD) since 1987 at 87 participating centers. This study aimed to evaluate the impact of COVID-19 among participants enrolled in the three arms of the registry: CKD, dialysis, and transplant. Methods: This was a retrospective cohort study of COVID-19 among participants in the NAPRTCS CKD, dialysis, and transplant registries from 2020 to 2022. Where appropriate, t-tests, chi-square analyses, and univariate logistic regression were used to evaluate the data. Results: The cohort included 1505 NAPRTCS participants with recent data entry; 260 (17%) had documented COVID-19. Infections occurred in all three registry arms, namely, 10% (n = 29) in CKD, 11% (n = 67) in dialysis, and 26% (n = 164) in transplant. The majority of participants (75%) were symptomatic. Hospitalizations occurred in 17% (n = 5) of participants with CKD, 27% (n = 18) maintenance dialysis participants, and 26% (n = 43) of transplant participants. Fourteen percent (n = 4) of CKD participants and 10% (n = 17) of transplant participants developed acute kidney injury (AKI), and a total of eight participants (one CKD, seven transplant) required dialysis initiation. Among transplant participants with moderate to severe illness, 40–43% developed AKI and 29–40% required acute dialysis. There were no reported deaths. Conclusions: COVID-19 was documented in 17% of active NAPRTCS participants. While there was no documented mortality, the majority of participants were symptomatic, and a quarter required hospitalization. [ABSTRACT FROM AUTHOR]

Background: Children with chronic kidney disease (CKD) are at risk for abnormalities in pubertal development. We aimed to describe the timing of pubertal onset by luteinizing hormone (LH) levels and the association between hormonal onset of puberty with changes in GFR. Methods: Data from the Chronic Kidney Disease in Children (CKiD) study were collected prospectively. GFR was estimated at annual visits and measured by iohexol clearance every other year. LH was measured from stored repository serum samples in a nested sample of 124 participants. Hormonal onset of puberty was defined as LH level greater than or equal to 0.3 IU/L. A mixed effects model with random intercepts and slopes was used to compare the slope of decline of GFR before and after hormonal onset of puberty. The model was adjusted for age, glomerular disease diagnosis, baseline proteinuria on the log scale, and BMI. Results: Median age at hormonal onset of puberty was 9.9 years (IQR 8.1, 11.9) in girls and 10.2 years (IQR 9.2, 11.0) in boys. The mixed effects model showed faster decline in both estimated GFR and measured GFR in boys after hormonal onset of puberty (p < 0.001), and a similar but attenuated accelerated estimated GFR decline was observed for girls with no difference for measured GFR. Conclusions: LH levels in the post-pubertal range were observed prior to clinical manifestations of puberty in children with CKD. Hormonal onset of puberty was associated with faster decline in GFR, particularly among boys with CKD. [ABSTRACT FROM AUTHOR]

An outbreak of SARS-CoV-2 (1 March to 10 May 2021) with an attack rate of 26.5% among approximately 1150 workers at a storage and distribution centre in England prompted a multidisciplinary outbreak investigation (5 May to 6 August 2021), with the aim of better understanding worker- and workplace-related risk factors for viral transmission in the warehousing sector. Overall, environmental factors (e.g., ventilation, humidity and temperature) were assessed to be appropriate at the facility. Nevertheless, 39 (51.3%) surface samples from across the site tested positive for low/ very low levels of SARS-CoV-2 RNA (Ct value ≥ 32.0 for all). Among the study participants, of whom 35.6% were confirmed or suspected cases, 95.5% reported having received COVID-19 prevention training, 100.0% reported handwashing, and 80.0% reported use of face coverings at work. Notably, 43.9% and 19.0% reported working with a symptomatic and a positive contact respectively. Furthermore, 80.5% and 46.3% had concerns regarding reduction in their income and future unemployment, respectively, due to self-isolation. The findings of this study suggest that, in addition to targeted workplace infection control measures and tailored work area specific risk assessments, an enhanced and equitable sick leave policy may help limit presenteeism and viral transmission in large workplaces. [ABSTRACT FROM AUTHOR]

Direct numerical simulation (DNS) of turbulent wall-bounded flows requires long streamwise computational domains to establish the correct spatial evolution of large-scale structures with high fidelity. In contrast, experimental measurements can relatively easily capture large-scale structures but struggle to resolve the dissipative flow scales with high fidelity. One methodology to overcome the shortcomings of each approach is by incorporating experimental velocity field measurements into DNS as an inflow boundary condition. This hybrid approach combines the strengths of DNS and experimental measurements, allowing for a reduction in the streamwise computational domain and accelerated development of large-scale structures in turbulent wall-bounded flows. To this end, this paper reports the results of an investigation to establish the impact of limited spatial resolution and limited near-wall experimental inflow data on the DNS of a wall-bounded turbulent shear flow. Specifically, this study investigates the spatial extent required for the DNS of a turbulent channel flow to recover the turbulent velocity fluctuations and energy when experimental inflow data is typically unable to capture fluctuations down to the viscous sub-layer or the smallest viscous scales (i.e. the Kolmogorov scale or their surrogate viscous scale in wall-bounded turbulent shear slows) is used as the inflow to a DNS. A time-resolved numerically generated experimental field is constructed from a periodic channel flow DNS (PCH-DNS) at R e τ = 550 and 2300, which is subsequently used as the inflow velocity field for an inflow–outflow boundary conditions DNS. The time-resolved experimental inflow field is generated by appropriately filtering the small scales from the PCH-DNS velocity by integrating over a spatial domain that is representative of a particle image velocimetry interrogation window. This study shows that the recovery of small scales requires a longer domain as the spatial resolution at the inflow decreases with all flow scales recovered and their correct scale-dependent energy is re-established once the flow has developed for 3 channel heights. [ABSTRACT FROM AUTHOR]

The digital humanities have developed in concert with online systems that increase the accessibility and speed of learning. Whereas previously students were immersed in the fluidity of campus life, they have become suspended and drawn-into various streams and currents of digital pedagogy, which articulate new forms of epistemological movement, often operating at speeds outside the lived time and rhythm of human thought. When assessing learning technologies, we have to consider the degree to which they complement the rhythms immanent to human thought, knowledge, investigation, and experimentation. In this paper, we examine learning from a humanities perspective, arguing that reading, writing, and thinking are ways of learning underscored by various genres of movement that segue with or diverge from the movements inherent to digital technologies, especially those deployed in learning systems. Using the work of thinkers such as John Dewey and Michel Serres, we examine the importance of movement in dialogue, where to truly learn involves embedding oneself in the flow of thought, accepting the flexibility of concepts, and aligning oneself with a community of thinkers. [ABSTRACT FROM AUTHOR]

Purpose: Vascular anomalies are classified as either vascular tumors or vascular malformations. Vascular malformations can be difficult to diagnose and treat in the pediatric population and can masquerade as malignant processes. Understanding the genetics behind vascular malformations can lead to identification of specific mutations which can be treated with targeted immunotherapy. Methods: Our case presents a pediatric patient with progressively enlarging vascular malformation despite multiple surgical resections and systemic medical treatments who underwent genetic evaluation and was found to have PIK3CA mutation. Results: After identification of PIK3CA mutation, our patient was successfully treated with the p110ɑ-specific inhibitor, alpelisib, with both shrinkage of malformation on follow-up imaging as well as gains in her developmental milestones. Conclusion: Progressive vascular malformations in the pediatric population can be hard to diagnose and treat and are thought to arise from somatic mutations. Our case highlights a patient with progressive malformation despite multiple surgical resections who was successfully treated with targeted immunotherapy after proper identification of genetic mutation. [ABSTRACT FROM AUTHOR]

A major clinical challenge today is the large number of bone defects caused by diseases or trauma. The development of three-dimensional (3D) scaffolds with adequate properties is crucial for successful bone repair. In this study, we prepared biomimetic mesoporous bioactive glass (MBG)-based scaffolds with and without ceria addition (up to 3 mol %) to explore the biological structure and chemical composition of the marine sponge Spongia Agaricina (SA) as a sacrificial template. Micro-CT examination revealed that all scaffolds exhibited a highly porous structure with pore diameters primarily ranging from 143.5 μm to 213.5 μm, facilitating bone ingrowth. Additionally, smaller pores (< 75 μm), which are known to enhance osteogenesis, were observed. The undoped scaffold displayed the highest open porosity value of 90.83%. Cytotoxicity assessments demonstrated that all scaffolds were noncytotoxic and nongenotoxic toward osteoblast cells. Moreover, scaffolds with higher CeO2 content promoted osteogenic differentiation of dental pulp stem cells, stimulating calcium and osteocalcin secretion. The scaffolds also exhibited antimicrobial and antibiofilm effects against Staphylococcus aureus (S. aureus) as well as drug delivery ability. Our research findings indicated that the combination of MBG, natural biological structure, and the addition of Ce exhibited a synergistic effect on the structure and biological properties of scaffolds for applications in bone tissue engineering. [ABSTRACT FROM AUTHOR]

A 42-year climate data record of global sea surface temperature (SST) covering 1980 to 2021 has been produced from satellite observations, with a high degree of independence from in situ measurements. Observations from twenty infrared and two microwave radiometers are used, and are adjusted for their differing times of day of measurement to avoid aliasing and ensure observational stability. A total of 1.5 × 1013 locations are processed, yielding 1.4 × 1012 SST observations deemed to be suitable for climate applications. The corresponding observation density varies from less than 1 km−2 yr−1 in 1980 to over 100 km−2 yr−1 after 2007. Data are provided at their native resolution, averaged on a global 0.05° latitude-longitude grid (single-sensor with gaps), and as a daily, merged, gap-free, SST analysis at 0.05°. The data include the satellite-based SSTs, the corresponding time-and-depth standardised estimates, their standard uncertainty and quality flags. Accuracy, spatial coverage and length of record are all improved relative to a previous version, and the timeseries is routinely extended in time using consistent methods. [ABSTRACT FROM AUTHOR]

This theme-based book review considers three recent titles focusing on public administration in China: Handbook of Public Policy and Public Administration in China, edited by Xiaowei Zang and Hon S. Chan; Governance and Public Administration in China, edited by Toby S. James, Wei Liu, and Caixia Man; and Public Administration and Governance in China: Chinese Insights with Global Perspectives, by Leizhen Zang and Yanyan Gao. [ABSTRACT FROM AUTHOR]

Multi-type characters, including uppercase and lowercase letters, symbols, and numbers, are essential in text entry activities. Although multi-type characters are used in passwords, instant messages, and document composition, there has been limited exploration of multi-character text entry for virtual reality head-mounted displays (VR HMDs). Typically, multi-type character entry requires four kinds of keyboards between which users need to switch. In this research, we explore hands-free approaches for rapid multi-type character entry. Our work explores two efficient and usable hands-free approaches for character selection: eye blinks and dwell. To enable quick switching between keyboards, we leverage the usability and efficiency of continuous head motions in the form of cross-based activation. In a pilot study, we explored the usability and efficiency of four locations of the switch keys, the two hands-free selection mechanisms, and crossing-based switching. In the main experiment, we evaluated four user-inspired layouts designed according to the findings from the pilot study. Results show that both blinking and dwell can work well with crossing-based switching and could lead to a relatively fast text entry rate (5.64 words-per-minute (WPM) with blinking and 5.42 WPM with dwell) with low errors (lower than 3% not corrected error rate (NCER)) for complex 8-digit passwords with upper/lowercase letters, symbols, and numbers. For sentences derived from the Brown Corpus, participants can reach 8.48 WPM with blinking and 7.78 WPM with dwell. Overall, as a first exploration, our results show that it is usable and efficient to perform hands-free text entry in VR using either eye blinks or dwell for character selection and crossing for mode switching. [ABSTRACT FROM AUTHOR]

Background: Injuries are common in adult recreational athletes. Exercise-based injury prevention programmes offer the potential to reduce the risk of injury and have been a popular research topic. Yet, syntheses and meta-analyses on the effects of exercise-based injury prevention programmes for adult recreational athletes are lacking. Objectives: We aimed to synthesise and quantify the pooled intervention effects of exercise-based injury prevention programmes delivered to adults who participate in recreation sports. Methods: Studies were eligible for inclusion if they included adult recreational athletes (aged > 16 years), an exercise-based intervention and used a randomised controlled trial design. Exclusion criteria were studies without a control group, studies using a non-randomised design and studies including participants who were undertaking activity mandatory for their occupation. Eleven literature databases were searched from earliest record, up to 9 June, 2022. The Physiotherapy Evidence Database (PEDro) scale was used to assess the risk of bias in all included studies. Reported risk statistics were synthesised in a random-effects meta-analysis to quantify pooled treatment effects and associated 95% confidence intervals and prediction intervals. Results: Sixteen studies met the criteria. Risk statistics were reported as risk ratios [RRs] (n = 12) or hazard ratios [HRs] (n = 4). Pooled estimates of RRs and HRs were 0.94 (95% confidence interval 0.80–1.09) and 0.65 (95% confidence interval 0.39–1.08), respectively. Prediction intervals were 0.80–1.09 and 0.16–2.70 for RR and HR, respectively. Heterogeneity was very low for RR studies, but high for HR studies (tau = 0.29, I2 = 81%). There was evidence of small study effects for RR studies, evidenced by funnel plot asymmetry and Egger's test for small study bias: − 0.99 (CI − 2.08 to 0.10, p = 0.07). Conclusions: Pooled point estimates were suggestive of a reduced risk of injury in intervention groups. Nevertheless, these risk estimates were insufficiently precise, too heterogeneous and potentially compromised by small study effects to arrive at any robust conclusion. More large-scale studies are required to clarify whether exercise-based injury prevention programmes are effective in adult recreational athletes. Clinical Trial Registration: The protocol for this review was prospectively registered in the PROSPERO database (CRD42021232697). [ABSTRACT FROM AUTHOR]

For decades, academic freedom and shared governance have stood as cornerstones of higher education in the United States, but these principles face unprecedented challenges. Recent developments point to a disturbing decline in these critical values, stirring debates on the future viability of the higher education system. This study delves into the problematic trajectory of modern higher education, spotlighting the rise of corporate practices within academic institutions, the swelling ranks of university administration, and the disproportionate weight given to student evaluations in assessing faculty. These factors have converged to push academia into an unstable transition, a liminal phase fueled by external and internal forces. This study examines the evolving landscape of academic freedom within the corporatized university model. Utilizing the concept of liminality, it explores the transitional challenges faced by academia in balancing traditional scholarly values with emerging market-driven paradigms, arguing that the corporatization of universities represents a liminal phase, wherein the identity and purpose of academic institutions are in flux, significantly impacting the notion of academic freedom. The shift toward a consumer-oriented ethos endangers the foundational principles of higher education, risking substituting educational substance with the mere transaction of educational services. The study concludes by issuing a call to action for all stakeholders in higher education to acknowledge and confront these detrimental trends, thereby safeguarding the principles of academic freedom, shared governance, and the educational system's overall integrity and dynamism. [ABSTRACT FROM AUTHOR]

The Eyes Absent proteins (EYA1-4) are a biochemically unique group of tyrosine phosphatases known to be tumour-promoting across a range of cancer types. To date, the targets of EYA phosphatase activity remain largely uncharacterised. Here, we identify Polo-like kinase 1 (PLK1) as an interactor and phosphatase substrate of EYA4 and EYA1, with pY445 on PLK1 being the primary target site. Dephosphorylation of pY445 in the G2 phase of the cell cycle is required for centrosome maturation, PLK1 localization to centrosomes, and polo-box domain (PBD) dependent interactions between PLK1 and PLK1-activation complexes. Molecular dynamics simulations support the rationale that pY445 confers a structural impairment to PBD-substrate interactions that is relieved by EYA-mediated dephosphorylation. Depletion of EYA4 or EYA1, or chemical inhibition of EYA phosphatase activity, dramatically reduces PLK1 activation, causing mitotic defects and cell death. Overall, we have characterized a phosphotyrosine signalling network governing PLK1 and mitosis. The Eyes Absent proteins (EYA1-4) are a group of tyrosine phosphatases. Here, the authors report a signalling pathway in which EYA4 and EYA1 dephosphorylate Polo-like kinase 1 (PLK1) at pY445 to support PLK1 activation and mitosis. [ABSTRACT FROM AUTHOR]

Background: Suicide, especially by firearm, remains a leading cause of death in military populations in the USA. Reducing access to firearms, especially during high risk times, may help prevent suicide and other forms of violence. The purpose of this study was to adapt a promising existing lethal means safety intervention (Project Safe Guard, PSG) for cross-cutting violence prevention and peer support in active-duty service communities using community engagement methods. Methods: A two-pronged community-engaged research approach was employed, including the Community Translation (CT) process that engaged 15 Service Members from one installation to help adapt PSG successfully. In addition, qualitative data was collected from 40 active-duty service members and military violence prevention specialists through in-depth interviews and focus group discussions. Results: Qualitative data and CT feedback led to site-specific PSG adaptations. Participants emphasized the importance of peer-to-peer discussions and highlighted resource allocation, leadership support, and stigma on firearm ownership as potential implementation challenges. Conclusions: Findings demonstrate the feasibility of community-engaged research to adapt lethal means safety interventions within military populations. PSG implementation should consider resource allocation, leadership support, and addressing stigma. This study has implications for future policies and standards for performing research on sensitive topics, particularly among military populations. [ABSTRACT FROM AUTHOR]

Declining Arctic sea ice is increasing polar bear land use. Polar bears on land are thought to minimize activity to conserve energy. Here, we measure the daily energy expenditure (DEE), diet, behavior, movement, and body composition changes of 20 different polar bears on land over 19–23 days from August to September (2019–2022) in Manitoba, Canada. Polar bears on land exhibited a 5.2-fold range in DEE and 19-fold range in activity, from hibernation-like DEEs to levels approaching active bears on the sea ice, including three individuals that made energetically demanding swims totaling 54–175 km. Bears consumed berries, vegetation, birds, bones, antlers, seal, and beluga. Beyond compensating for elevated DEE, there was little benefit from terrestrial foraging toward prolonging the predicted time to starvation, as 19 of 20 bears lost mass (0.4–1.7 kg•day−1). Although polar bears on land exhibit remarkable behavioral plasticity, our findings reinforce the risk of starvation, particularly in subadults, with forecasted increases in the onshore period. Declining Arctic sea ice is increasing polar bear land use. Here, the authors follow 20 different polar bears on land over 3 years and measure daily energy expenditure finding that despite behavioural and diet plasticity the bears are at risk of starvation. [ABSTRACT FROM AUTHOR]

Background: In the UK, it is estimated that there are 250,000 burn injuries each year. Appropriate management of burns requires targeted education for physicians managing burns within emergency units, primary care, and specialised hospital units. Prior research has shown a deficit in exposure to plastic surgery and burn-related teaching during undergraduate studies. The purpose of this study was to investigate the level of undergraduate knowledge, confidence, and teaching in burns within multiple cohorts of penultimate and final-year medical students based across medical schools within the UK. Methods: We utilised a validated online questionnaire, disseminated to medical students in their penultimate and final years, via the UK Plastics Research Collaborative’s local university leads, employing a well-known survey platform (Google Forms). Results: Out of the 950 responses received from 10 medical schools, 34% (n = 323) reported no burn-related instruction until the current academic year. Overall, 63.8% of students were not confident in assessing total body surface burns, 57.3% were not confident in initiating burn first aid management, and 69.5% were not confident in calculating fluid requirements for resuscitation. Moreover, 84.2% felt that they had not received adequate teaching in burns during their undergraduate training. Conclusions: This study demonstrates a lack of undergraduate exposure, teaching, and confidence in the basics of burn assessment and management. It calls for enhanced training at the undergraduate level, potentially incorporating simulation training to boost confidence in burn management. Level of evidence: Not ratable. [ABSTRACT FROM AUTHOR]

Multiple correspondence analysis (MCA) has started to gain popularity within sociology as a method of mapping 'fields' and 'social spaces' in the style of Pierre Bourdieu, its capacity to document multidimensional geometric relationships within data being a snug fit for the relational mode of thought he championed. There is a risk, however, of over-relying on MCA when the data suggest alternative methods and, as a result, drawing unsound conclusions. As a case in point, I take a recent analysis of political attitudes in the UK using MCA that drew bold inferences about the relationship with social class and reanalyse the same data with categorical principal components analysis (CatPCA). The results suggest the opposite conclusion to what was originally argued. I thus urge greater methodological flexibility and openness among those wishing to chart fields and social spaces and, more specifically, I make a case for CatPCA as a tool of geometric data analysis. [ABSTRACT FROM AUTHOR]

Cochlear melanocytes are intermediate cells in the stria vascularis that generate endocochlear potentials required for auditory function. Human PAX3 mutations cause Waardenburg syndrome and abnormalities of skin and retinal melanocytes, manifested as congenital hearing loss (~ 70%) and hypopigmentation of skin, hair and eyes. However, the underlying mechanism of hearing loss remains unclear. Cochlear melanocytes in the stria vascularis originated from Pax3-traced melanoblasts and Plp1-traced Schwann cell precursors, both of which derive from neural crest cells. Here, using a Pax3-Cre knock-in mouse that allows lineage tracing of Pax3-expressing cells and disruption of Pax3, we found that Pax3 deficiency causes foreshortened cochlea, malformed vestibular apparatus, and neural tube defects. Lineage tracing and in situ hybridization show that Pax3+ derivatives contribute to S100+, Kir4.1+ and Dct+ melanocytes (intermediate cells) in the developing stria vascularis, all of which are significantly diminished in Pax3 mutant animals. Taken together, these results suggest that Pax3 is required for the development of neural crest cell-derived cochlear melanocytes, whose absence may contribute to congenital hearing loss of Waardenburg syndrome in humans. [ABSTRACT FROM AUTHOR]

Performing quality assurance checks on hydrochemical data prior to interpreting these data is important as shown in this case study. The informative hydrochemistry paper authored by Mora et al. (Environ Monit Assess 189:394–408, 2017. https://doi.org/10.1007/s10661-017-6096-y) presents a significant amount of hydrogeochemical data for 30 large-yield wells, interpretation (including advanced statistics), findings, and conclusions for the Monterrey metropolitan area (MMA), Mexico. The author concludes that the probable analytical inaccuracy (notable bias and imprecision) and data conversion errors contained in the Mora et al. (2017) paper do not appreciably impact negatively their hydrogeochemical findings and conclusions. The author performed the cation–anion balance (CAB) quality assurance (QA) check method and discovered systematic error (bias) ranging from − 20.8% (Well S1) to 16.5% (Well S9), with 14 well analyses associated with CAB errors ≥ 5.0%. Coupling this simple but effective QA check with other QA algorithms, the author determined for nine well major-ion analyses, HCO3 concentrations were notably low, and 10 well analyses were identified as possessing anomalously low Ca concentrations. These QA check methods will enhance: (1) the accuracy and defensibility of analytical results, and (2) potentially the interpretation and findings of hydrochemical investigations. Additionally, this paper provides new hydrogeochemical evaluation, interpretation, and findings for the MMA, i.e., Na/Cl molar ratios ≤ 0.88 for six studied wells strongly suggest that the groundwater supplying these wells has been impacted by seawater intrusion most likely sourced by the Western Interior Seaway. At least four of these wells occur in an area underlain by marine sedimentary rocks. [ABSTRACT FROM AUTHOR]

Under climate change, model ensembles suggest that declines in phytoplankton biomass amplify into greater reductions at higher trophic levels, with serious implications for fisheries and carbon storage. However, the extent and mechanisms of this trophic amplification vary greatly among models, and validation is problematic. In situ size spectra offer a novel alternative, comparing biomass of small and larger organisms to quantify the net efficiency of energy transfer through natural food webs that are already challenged with multiple climate change stressors. Our global compilation of pelagic size spectrum slopes supports trophic amplification empirically, independently from model simulations. Thus, even a modest (16%) decline in phytoplankton this century would magnify into a 38% decline in supportable biomass of fish within the intensively-fished mid-latitude ocean. We also show that this amplification stems not from thermal controls on consumers, but mainly from temperature or nutrient controls that structure the phytoplankton baseline of the food web. The lack of evidence for direct thermal effects on size structure contrasts with most current thinking, based often on more acute stress experiments or shorter-timescale responses. Our synthesis of size spectra integrates these short-term dynamics, revealing the net efficiency of food webs acclimating and adapting to climatic stressors. Using a global synthesis of size spectra data from pelagic food webs, this study finds that size structure is not driven by temperature as often suggested, but by the nutrient status of the system. This means that modest phytoplankton declines projected for key fishing grounds at mid-latitudes will amplify into substantial reductions in the supportable biomass of fish. [ABSTRACT FROM AUTHOR]

The study explored the dependence of the spatio-temporal pattern of rainfall and its variability on the spatial distribution of forests in the central Indian landscape, which covers ~1 million km2, includes five states, and supports a population of 329 million people. The monsoon rainfall is, thus, a crucial source of freshwater for these population. We analyzed the relationship between rainfall and satellite-derived vegetation vigor, vegetation fraction, and elevation across 22 experimental zones across central India (i.e., forested, non-forested, and agricultural regions; buffer zones within and outside forests). Around 87% of annual rainfall is received during the monsoon, with maximum rainfall (~1600 mm) in Odisha and minimum (~900 mm) in Maharashtra. The average rainfall was greater (~1500 mm) inside forests than in non-forested regions (~1000 mm). Moreover, 245 mm km−2 year−1 of rainfall was observed over forests during monsoon, but only 215 mm km−2 year−1 in non-forested areas. Overall, rainfall increases from the forest edge towards the forest core logarithmically at a rate of ~10 mm km−1 year−1, and it decreases exponentially when moving away from the forest edge at an average rate of −20 mm km−1 year−1 over 0-to-50 km range, and at a rate of −7.5 mm km−1 year−1 over the 50-to-100 km range. This rate of decrease was maximum in Madhya Pradesh and Jharkhand and minimum in Chhattisgarh. The results confirmed the crucial role of forests in the distribution of monsoon rainfall, but in the elevated and Western Ghats regions, the orographic effect is dominant. These findings are of great concern to forest policymakers to conserve and protect the central Indian forests. [ABSTRACT FROM AUTHOR]

Objective: Image-guided biopsy is well-established in the diagnosis of musculoskeletal lesions. While several studies have demonstrated a high diagnostic yield in image-guided biopsy, there are no current guidelines around procedural factors such as number of cores. Furthermore, there have been mixed results regarding which lesions are more favourable to a diagnostic biopsy. We wanted to evaluate diagnostic yield and concordance for image-guided biopsies for musculoskeletal lesions. The null hypothesis was that there are no controllable factors that contribute to positive yield. Materials and methods: Retrospective review of consecutive patients who underwent image-guided biopsy at a large teaching hospital for musculoskeletal lesions discussed at the sarcoma multi-disciplinary meeting. The formal biopsy histology report was evaluated, and biopsies were considered diagnostic or non-diagnostic. In those that had subsequent surgery (by wide excision or open biopsy), final and initial histology was compared and biopsies were considered concordant or not. Overall diagnostic yield and concordance were calculated. Statistical analysis was performed with Stata 13.0 (StataCorp). Results: Over the 14-year period, 429 biopsies were included. Diagnostic yield was 85% and concordance was 100%. No cases of malignant lesions were initially called benign on biopsy. One biopsy had a complication (0.2%). Factors associated with higher diagnostic yield included soft tissue versus bone lesions, three or more cores and longer total specimen length. Factors that were not associated included core size, use of FNA cytology, gender, age, benign versus malignant, anatomic location and lesion appearance. Conclusion: The null hypothesis is rejected. The main predictor of diagnostic biopsy was total specimen length, independent of number of cores taken. Three or more cores and longer cores are optimal, though these factors are influenced by lesion biology and not always able to be controlled. [ABSTRACT FROM AUTHOR]