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Future climate presents conflicting implications for forest biomass. We evaluate how plant hydraulic traits, elevated CO2 levels, warming, and changes in precipitation affect forest primary productivity, evapotranspiration, and the risk of hydraulic failure. We used a dynamic vegetation model with plant hydrodynamics (FATES-HYDRO) to simulate the stand-level responses to future climate changes in a wet tropical forest in Barro Colorado Island, Panama. We calibrated the model by selecting plant trait assemblages that performed well against observations. These assemblages were run with temperature and precipitation changes for two greenhouse gas emission scenarios (2086-2100: SSP2-45, SSP5-85) and two CO2 levels (contemporary, anticipated). The risk of hydraulic failure is projected to increase from a contemporary rate of 5.7% to 10.1-11.3% under future climate scenarios, and, crucially, elevated CO2 provided only slight amelioration. By contrast, elevated CO2 mitigated GPP reductions. We attribute a greater variation in hydraulic failure risk to trait assemblages than to either CO2 or climate. Our results project forests with both faster growth (through productivity increases) and higher mortality rates (through increasing rates of hydraulic failure) in the neo-tropics accompanied by certain trait plant assemblages becoming nonviable.

Abstract Grasslands cover approximately a third of the Earth’s land surface and account for about a third of terrestrial carbon storage. Yet, we lack strong predictive models of grassland plant biomass, the primary source of carbon in grasslands. This lack of predictive ability may arise from the assumption of linear relationships between plant biomass and the environment and an underestimation of interactions of environmental variables. Using data from 116 grasslands on six continents, we show unimodal relationships between plant biomass and ecosystem characteristics, such as mean annual precipitation and soil nitrogen. Further, we found that soil nitrogen and plant diversity interacted in their relationships with plant biomass, such that plant diversity and biomass were positively related at low levels of nitrogen and negatively at elevated levels of nitrogen. Our results show that it is critical to account for the interactive and unimodal relationships between plant biomass and several environmental variables to accurately include plant biomass in global vegetation and carbon models.

Abstract Background Under South Africa’s Universal Test and Treat (UTT) policy, CD4 counts are no longer required to determine HIV treatment eligibility. However, CD4 count at presentation remains an important marker of disease progression. We assessed whether CD4 testing declined in the UTT era and, if so, by how much. Methods We analysed CD4 count data from the National Health Laboratory Service (NHLS) National HIV Cohort and TIER.Net database for individuals in HIV care across five South African provinces. “First CD4 count” was defined as the first CD4 test recorded for each patient. In TIER.Net, “date of presentation” was the earliest date of HIV testing, CD4 measurement, or clinic visit. Trends in first CD4 testing volumes (2004–2018) were analyzed, with interrupted time-series analyses assessing the impact of UTT (September 2016). Results Data included 5,274,218 (NHLS) and 2,265,557 (TIER.Net) individuals with a first CD4 count. In NHLS, first CD4 counts increased from 47,604 in 2004 to 383,705 in 2010 and then declined. Lower volumes were recorded in TIER.Net. Adjusting for prior trends, first CD4 counts increased slightly after UTT, by 32 individuals/day in NHLS (95% CI: − 6 to 61) and 88 individuals/day in TIER.Net (95% CI: 30 to 148). Among TIER.Net patients, the percentage with a CD4 count decreased by 4.3% (95% CI: − 5.2 to − 3.0%). Conclusions We found no major decline in CD4 testing at presentation following UTT, contrasting findings from resource-constrained settings with greater reliance on external donors.

Technology has expanded the landscape of higher education. The ability to learn almost anything from anywhere at any time has impacted educational attainment, particularly for those who lacked access in the past. Many who enter the virtual classroom, however, do not stay. Completion rates for online learning fall short, especially when compared to in-person experiences. For all its advancements, online learning has also created a chasm in human connection that influences learning. We are not made to connect through wires. Though we may espouse having multitudes of "friends" online, developing a true sense of belonging and connection must be purposefully developed when working through a screen and keyboard. This reflective essay interrogates the use of technology in higher education and encourages the inclusion of positive psychology practices to bridge the gap of human connection that is an integral part of student success.

Atrial infarction is often undiagnosed in patients with underlying ischemic heart disease and is identified only later, upon autopsy. One of the main challenges in diagnosing the condition is its localization within the affected atria. Treatment of atrial infarction focuses on acute reperfusion therapy, long-term management of cardiovascular disease risk factors, consideration of antiarrhythmia medications, and anticoagulation therapy. This review covers the anatomy of the atrial vasculature, complications associated with atrial infarction, diagnostic criteria for use of electrocardiography and other imaging modalities, and overall prognosis and management.

Mutations of the Cullin-3 (Cul3) E3 ubiquitin ligase are associated with autism and schizophrenia, neurological disorders characterized by sleep disturbances and altered synaptic function. Cul3 engages dozens of adaptor proteins to recruit hundreds of substrates for ubiquitination, but the adaptors that impact sleep and synapses remain ill-defined. Here we implicate Insomniac (Inc), a conserved protein required for normal sleep and synaptic homeostasis in Drosophila, as a Cul3 adaptor. Inc binds Cul3 in vivo, and mutations within the N-terminal BTB domain of Inc that weaken Inc-Cul3 associations impair Inc activity, suggesting that Inc function requires binding to the Cul3 complex. Deletion of the conserved C-terminus of Inc does not alter Cul3 binding but abolishes Inc activity in the context of sleep and synaptic homeostasis, indicating that the Inc C-terminus has the properties of a substrate recruitment domain. Mutation of a conserved, disease-associated arginine in the Inc C-terminus also abolishes Inc function, suggesting that this residue is vital for recruiting Inc targets. Inc levels are negatively regulated by Cul3 in neurons, consistent with Inc degradation by autocatalytic ubiquitination, a hallmark of Cullin adaptors. These findings link Inc and Cul3 in vivo and support the notion that Inc-Cul3 complexes are essential for normal sleep and synaptic function. Furthermore, these results indicate that dysregulation of conserved substrates of Inc-Cul3 complexes may contribute to altered sleep and synaptic function in autism and schizophrenia associated with Cul3 mutations.

Oligo-deoxythymidine (oligo-dT) ligand-based affinity chromatography is a robust method for purifying mRNA drug substances within the manufacturing process of mRNA-based products, including vaccines and therapeutics. However, the conventional batch mode of operation for oligo-dT chromatography has certain drawbacks that reduce the productivity of this process. Here, we report a new continuous oligo-dT chromatography process for the purification of in vitro transcribed mRNA, which reduces losses, improves the efficiency of oligo-dT resin use, and intensifies the chromatography process. Furthermore, the quality by design (QbD) framework was used to establish a design space for the newly developed method. The optimization of process parameters (PPs), including salt type, salt concentration, load flow rate and mRNA load concentration both in batch and the continuous mode, achieved a greater than 90% yield (mRNA recovery) along with greater than 95% mRNA integrity and greater than 99% purity. The productivity of continuous chromatography was estimated to be 5.75-fold higher, and the operating cost was estimated 15% lower, when compared with batch chromatography. Moreover, the QbD framework was further used to map the relationship between critical quality attributes and key performance indicators as a function of critical process parameters and critical material attributes.

Nicola Luigi Bragazzi,1– 4 Hicham Khabbache,5 Khalid Ouazizi,6 Driss Ait Ali,6 Hanane El Ghouat,6 Laila El Alami,6 Hisham Atwan,7 Ruba Tuma,8– 10 Nomy Dickman,10 Raymond Farah,10,11 Rola Khamisy-Farah9,10 1Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Parma, Italy; 2Laboratory for Industrial and Applied Mathematics (LIAM), Department of Mathematics and Statistics, York University, Toronto, ON, Canada; 3Postgraduate School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy; 4United Nations Educational, Scientific and Cultural Organization (UNESCO) Chair, Health Anthropology Biosphere and Healing Systems, University of Genoa, Genoa, Italy; 5Director of the UNESCO Chair “Lifelong Learning Observatory” (UNESCO/UMSBA), Fez, Morocco; 6Department of Psychology, Faculty of Arts and Human Sciences Fès-Saïss, Sidi Mohamed Ben Abdellah University, Fez, Morocco; 7Department of Internal Medicine, Kaplan Medical Centre, Hebrew University, Rehovot, Israel; 8Department of Obstetrics and Gynecology, Galilee Medical Center, Nahariya, Galilee, Israel; 9Clalit Health Services, Akko, Israel; 10Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; 11Department of Internal Medicine B, Ziv Medical Center, Safed, IsraelCorrespondence: Nicola Luigi Bragazzi, Human Nutrition Unit (HNU), Department of Food and Drugs University of Parma, Via Volturno 39, Parma, 43125, Italy, Tel +39 0521 903121, Email nicolaluigi.bragazzi@unipr.itPurpose: Sex and Gender-Based Medicine (SGBM) addresses the influence of sex and gender on health and healthcare, emphasizing personalized care. Integrating SGBM into medical education is challenging. This study examines the implementation of an SGBM course in an Israeli university during the first year of the medical school.Methods: The course integrated lectures, group work, online gender studies resources, workshops, teacher training, and essential literature. The curriculum spanned pre-clinical and clinical aspects, featuring seven 90-minute sessions. Surveys assessed course structure, content, and lecturers using a 5-point Likert scale and qualitative feedback. Quantitative analysis involved descriptive statistics, and thematic analysis was used for qualitative data.Results: Of the 84 students surveyed, 35 (41.7%) responded to the first part, and 30 (35.7%) to the second. The SGBM course received high satisfaction with an average score of 3.63, surpassing other first-year courses (average 3.21). Students appreciated the supportive academic atmosphere (mean score 4.20) and diverse teaching methods (mean score 4.03), while the development of feminist thinking was less appreciated (average score 3.49). Lecturers received high ratings (average score 4.33). Qualitative feedback highlighted the value of group work, the significance of the subject matter, and the helpfulness of supplementary videos. Students requested more content on contemporary issues like gender transition and patient perspectives. The feminist medicine aspect was contentious, with students seeking better gender balance and scientific evidence.Conclusion: Introducing SGBM into the first-year curriculum yielded positive results with high student satisfaction for content and lecturers. An expanded course module is planned, to be assessed at the end of the next academic year.Keywords: sex- and gender-based medicine, medical education, medical training, curriculum integration

The cheetah Acinonyx jubatus has suffered considerable range contractions in recent decades. Despite the importance of up-to-date information on distribution to guide conservation, such information is lacking for large areas within the species’ remaining potential range. In Tanzania, the largest tract of potential cheetah habitat without such data is the Selous–Nyerere ecosystem. Although the cheetah is considered possibly extant in this landscape, the last confirmed sighting was in the late 1990s. During 2020–2022, we carried out sign-based (spoor) and camera-trap surveys across Selous Game Reserve and Nyerere National Park. We did not record any evidence of cheetah presence, and opportunistic enquiries with tourism operators and protected area management staff did not provide any evidence of current or recent presence. Our findings suggest that current cheetah presence is unlikely, and that Selous–Nyerere should not be treated as potential contemporary cheetah range. We discuss the possibility that Selous–Nyerere may have never hosted a resident cheetah population, and was either occasionally occupied by dispersers from other populations or represented the edge of populations that spanned areas now treated as corridors.

Nocturnal polyuria (NP) is a leading cause of nocturia in adults. While diagnostic criteria for NP have been established in adult men, they have not been validated in other demographic groups including women, adolescents, and children, and little is known about appropriate reference values in these populations. Accordingly, the present study aimed to determine an hourly nocturnal urine production (NUP) rate in adolescents most predictive of the presence of nocturia. We analyzed prospectively collected data of 100 male and female adolescents aged 10-18 years. All subjects completed nocturnal voiding diaries and significant nocturia was defined as ≥1 or more voids per night. Receiver operating characteristic (ROC) curves were used to test the performance of different NUP values in predicting nocturia. On ROC, the area under curve (AUC) was 0.85. On multivariable logistic regression with variables of sex, obesity, and elevated blood pressure, adding NUP as a categorical variable maximally increased the predictive value of the model upon utilizing a cutoff of 50 ml/h, increasing the R2 from 0.491 to 0.683. A NUP >50 ml/h had a sensitivity of 62.2% and a specificity of 96.4% in predicting nocturia. A cut-off value of NUP >50 ml/h may be relevant to the clinical management of adolescents with nocturia.

Cisplatin, a commonly used chemotherapy drug, is well-established for its ototoxic effects, primarily attributed to the damage it inflicts on cochlear hair cells. However, its impact on the vestibular system remains inadequately understood. Here, we provide a comprehensive review of existing literature concerning cisplatin-induced vestibulotoxicity. Animal studies have shown that cisplatin induces a vestibular hair cell loss that is dose-dependent, with the severity of damage also varying according to the route of administration. Notably, intratympanic and systemic injections in animal models have manifested significant damage primarily to utricular hair cells, with a lesser degree of damage observed for the other vestibular end organs. The underlying mechanisms of cisplatin induced vestibular hair cell loss include apoptosis, oxidative stress, and inflammatory cytokines. Several protective agents, such as Pifithrin-α, DAPT, Ginkgolide B, and heat shock proteins, have demonstrated efficacy in inhibiting cisplatin-induced vestibular damage in preclinical studies. Human clinical findings indicate that cisplatin treatment can cause vestibular dysfunction, characterized by symptoms ranging from transient dizziness to persistent vertigo. Challenges in diagnosis, including the limited utilization of comprehensive vestibular testing for many patients, contribute to the variability in reported outcomes. Cisplatin-induced vestibulotoxicity is a significant complication of chemotherapy, necessitating further research to understand its mechanisms and to improve diagnosis and management, ultimately aiming to enhance the quality of life for cancer patients undergoing cisplatin therapy.

IntroductionApproximately 75% of caregivers providing unpaid care to family members or friends experience persistent pain. Simultaneously, individuals who require caregiving commonly experience pain. The inherent complexity of pain is enhanced by relationship dynamics of two closely tied individuals (i.e., caregiving dyad = caregivers and care recipients). Currently there are no proven pain interventions that target the caregiving dyad. Thus, the purpose of this pilot study was to assess the feasibility of a new behavioral multi-modal intervention, the Merging Yoga and self-management to develop Skills (MY-Skills) intervention.MethodsEach participant was part of a caregiving dyad and all participants had moderate to severe musculoskeletal pain, a score of ≥4 of 6 on the short mini-mental status exam, were ≥18 years old, sedentary, able to speak English, able to stand, and living at home. Participants were randomized to MY-Skills or the control group. MY-Skills was offered twice a week for eight weeks and each two-hour session included yoga and self-management education developed specifically for caregiving dyads experiencing persistent pain. MY-Skills was group based and developed as an in-person intervention. Due to Covid-19, the intervention was moved online and data are presented for in-person and online cohorts. Benchmarks for feasibility were set a priori, addressing: recruitment, attrition, attendance, safety, acceptability/satisfaction, and study completion.ResultsThirteen participants completed the in-person MY-Skills intervention (caregivers n = 7, care-receivers n = 6) and 18 individuals completed the online MY-Skills intervention (9 dyads). Most participants had pain for ≥10 years. Recruitment and attrition benchmarks for the in-person intervention were not met; yet they were met for the online version. In-person and online MY-Skills intervention attendance, safety, acceptability/satisfaction, and completion exceeded benchmark criteria.DiscussionThe MY-Skills intervention appears feasible and acceptable, however changes to recruitment criteria are necessary. Additional testing and larger sample sizes are required to test efficacy. Trial registrationClinicaltrials.gov, #NCT03440320.

Abstract Public policy addressing biodiversity loss is most likely to be effective when it is informed by appropriate evidence and considers potential unintended consequences. We evaluate key evidence relating to the Hunting Trophies (Import Prohibition) Bill that was discussed in the UK Parliament between 2022 and 2024. We characterize the UK's role in international hunting trophy trade by analyzing CITES (Convention on International Trade in Endangered Species of Wild Fauna and Flora) trade data for 2000–2021 and 2015–2021. For CITES‐listed species imported to/exported from the UK as hunting trophies in these periods we use data from the International Union for Conservation of Nature (IUCN) Red List of Threatened Species to determine whether hunting designated as “trophy hunting” is (i) likely a major threat contributing to species being of elevated conservation concern, (ii) likely or possibly causing localized declines, or (iii) not a threat. We then use the Red List to determine whether such hunting provides, or potentially provides, benefits for species and/or people. Finally, we evaluate the UK Government's impact assessment of the bill. In 2000–2021 an estimated 3494 hunting trophies from 73 CITES‐listed species and subspecies were exported to the UK involving an estimated 2549 whole organism equivalents (WOEs), that is, individual animals. Imports involved 158.86 ± 66.53 (mean ± SD) trophies/year (115.83 ± 32.27 WOEs/year). In 2015–2021, 79% of imports were from countries where populations of the hunted species are stable, increasing, or abundant. Legal hunting for trophies is not a major threat to any of the species or subspecies imported to the UK, but likely or possibly represents a local threat to some populations of eight species. This hunting does, or could potentially, benefit 20 species and subspecies, and people. Among other concerns, the impact assessment failed to adequately consider the costs and benefits to local communities in countries where such hunting occurs. Informed by these analyses we discuss alternative regulatory options.

Purpose: We describe a patient after customized crosslinking (CXL) for progressive keratoconus who developed corneal edema with spontaneous resolution. Observations: A 24-year-old male with progressive keratoconus of the left eye underwent a customized CXL procedure with a total energy of 10 J/cm2 for 16.4 minutes. Preoperative corrected distance visual acuity (CDVA) was 20/30 with a maximum keratometry (K)-value of 58.6 diopter (D) and the thinnest point measured 414 μm. The preoperative endothelial cell density (ECD) was 2414 cells/mm2. During treatment, corneal thickness was 325 μm after epithelial debridement and 375 μm after the application of 0.1 % riboflavin containing HPMC. After the treatment, antibiotic and steroid drops were prescribed for 5 days and 3 weeks, respectively. At the 1-month post-CXL visit the patient had no complaints, visual acuity and clinical examination showed no irregularities. At the 4-months post-CXL visit the patient complained of blurry vision. The CDVA was 20/100 and slit-lamp examination showed microcystic corneal edema. The corneal thickness at the thinnest point measured 440 μm. One month later the edema had resolved spontaneously and CDVA had restored to 20/25. Corneal thickness at the thinnest point measured 415 μm, the ECD was 1514 cells/mm2 and confocal microscopy showed normal structural changes in the anterior stroma after CXL, with the demarcation line located at a depth of 414 μm, just above the corneal endothelium. Conclusions and importance: We report a case of corneal edema following customized CXL with endothelial cell loss that resolved spontaneously. We recommend either adhering to a minimal stromal thickness of 400 μm before administering UV-A irradiation, using a contact lens or adjusting the irradiation to prevent this complication.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). Commonly used methods for both clinical diagnosis of SARS-CoV-2 infection and management of infected patients involve the detection of viral RNA, but the presence of infectious virus particles is unknown. Viability PCR (v-PCR) uses a photoreactive dye to bind non-infectious RNA, ideally resulting in the detection of RNA only from intact virions. This study aimed to develop and validate a rapid v-PCR assay for distinguishing intact and compromised SARS-CoV-2. Propidium monoazide (PMAxx) was used as a photoreactive dye. Mixtures with decreasing percentages of intact SARS-CoV-2 (from 100% to 0%) were prepared from SARS-CoV-2 virus stock and a clinical sample. Each sample was divided into a PMAxx-treated part and a non-PMAxx-treated part. Reverse transcription-PCR (RT-PCR) using an in-house developed SARS-CoV-2 viability assay was then applied to both sample sets. The difference in intact SARS-CoV-2 was determined by subtracting the cycle threshold (Ct) value of the PMAxx-treated sample from the non-PMAxx-treated sample. Mixtures with decreasing concentrations of intact SARS-CoV-2 showed increasingly lower delta Ct values as the percentage of intact SARS-CoV-2 decreased, as expected. This relationship was observed in both high and low viral load samples prepared from cultured SARS-CoV-2 virus stock, as well as for a clinical sample prepared directly from a SARS-CoV-2 positive nasopharyngeal swab. In this study, a rapid v-PCR assay has been validated that can distinguish intact from compromised SARS-CoV-2. The presence of intact virus particles, as determined by v-PCR, may indicate SARS-CoV-2 infectiousness.IMPORTANCEThis study developed a novel method that can help determine whether someone who has been diagnosed with coronavirus disease 2019 (COVID-19) is still capable of spreading the virus to others. Current tests only detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, but cannot tell whether the particles are still intact and can thus infect cells. The researchers used a dye that selectively blocks the detection of damaged virions and free RNA. They showed that this viability PCR reliably distinguishes intact SARS-CoV-2 capable of infecting from damaged SARS-CoV-2 or free RNA in both cultured virus samples and a clinical sample. Being able to quickly assess contagiousness has important implications for contact tracing and safely ending isolation precautions. This viability PCR technique provides a simple way to obtain valuable information, beyond just positive or negative test results, about the actual risk someone poses of transmitting SARS-CoV-2 through the air or surfaces they come into contact with.

Introduction Linked administrative data are widely used in epidemiology to capture patient data across multiple databases. Linkage error rates, critical to measure linkage performance, are rarely reported due to difficulty in obtaining representative gold standard. We propose a training and validation approach for linkage procedures that yield unbiased performance estimates even with a non-representative gold standard. Methods We linked patient records from two non-deduplicated databases for HIV monitoring in South Africa, TIER.Net and NHLS laboratory database, using a network-based probabilistic linkage and deduplication approach. National IDs (gold standard) were available for a non-representative minority of records (10%). We calculated sensitivity (Sen, share of true matches identified by the algorithm) and positive predictive value (PPV, share of algorithm-identified matches that were true matches). We adjusted for bias due to informative missingness in National IDs using inverse probability weights to break the link between missingness and match probability. Results 111,755 record pairs were considered. National IDs were not missing completely at random. Match probabilities for National ID record pairs exhibited substantially less uncertainty (mid-range match probabilities), inflating Sen and PPV. Before bias correction, Sen and PPV were estimated at 97.0% and 97.8% respectively. After bias correction for missing National IDs, Sen and PPV were estimated at 95.7% and 96.6%. Failure to address this bias understated the overlinkage rate (100% - PPV) by 35% and the underlinkage rate (100% - Sen) by 30%. Conclusion Failure to adjust for informative missingness in the gold standard may lead to biased validation metrics and over/underconfidence in linked data.

Background HIV cohort data are crucial for understanding the effects of HIV infection and treatment. Linkage between HIV clinical and population records unlocks potential to understand the cause and consequences of social-economic factors on HIV-care seeking behaviors and mortality outcomes. We created HIV data infrastructure by linking HIV treatment records with routinely collected records. Methods We linked HIV cohort data(n=119,434) to Health and Demographic Surveillance(n=256,425), laboratory tests(n=617,314), clinic visits and hospital admissions(n=170,325) from KwaZulu-Natal, an HIV-endemic setting in rural South Africa. We used graph-based probabilistic record linkage algorithm to link the data for HIV patients accessing care at 17 clinics within the Hlabisa sub-district. Africa Health Research Institute (AHRI) has collected health and demographic surveillance data since 2000. AHRI has set up a hospital information system in the district to capture ICD-10 code admissions and discharges. Results From the 5% sample of 462,524 linkage clusters, the computed F-score was 0.88, sensitivity was 88% and positive predictive value was 91%. 38.5% of the patient ID clusters contained records linked across multiple databases. 36% of the HIV patient ID clusters contained records linked with laboratory tests. 19.5% of the HIV patient ID clusters contained data on demographic surveillance. 12.5% of the HIV patient ID clusters contained records linked with clinic visits and hospital admissions. 4% of patient IDs contained records across all four databases. Conclusion We have successfully created a cross-sectorial HIV cohort through probabilistic record linkage methods. The cohort provides a platform to answer policy-relevant questions.