ABSTRACT
There is growing concern about the fate of tropical forests in the face of rising global temperatures. Doughty et al. (2023) suggest that an increase in air temperature beyond ∼4 °C will ...result in massive death of tropical forest leaves and potentially tree death. However, this prediction relies on assumptions that likely underestimate the heat tolerance of tropical leaves.
Tropical tree leaves have greater heat tolerance than previously assumed by some scientists.
Population serological testing (specifically measuring SARS-CoV-2-specific IgG antibody titres) can estimate the total number of infections by assessing the number of individuals who have mounted an ...immune response, regardless of whether an infection was subclinical or happened in the recent past (current data suggest antibodies persist for at least 4 weeks).8 By providing estimates of who is and is not immune to SARS-CoV-2, serological data can be used in at least four ways. ...to strategically deploy immune health-care workers to reduce exposure of the virus to susceptible individuals. ...to assess the effect of non-pharmaceutical interventions at the population-level and inform policy changes to release such measures, Fourth, to identify individuals who mounted a strong immunological response to the virus and whose antibody isolates can be used to treat patients via plasma therapy.9 Although the potential for serological assays to help control the COVID-19 pandemic is substantial, the complexity of developing and validating a diagnostic test is not fully elucidated by Yong and colleagues.4 Serological assays are currently being developed for widespread use.10 Yet, several challenges remain: first, assessing the sensitivity and specificity of tests, particularly for determining disease during the acute phase of infection; second, verifying the test is not detecting cross-reactivity with other viral pathogens that result in false-positive results; third, understanding antibody kinetics over time to distinguish thresholds of immunity, because we do not know how long immunity to this novel coronavirus might last; and finally, ensuring the test is reliable for distribution and is cost-efficient.
Rainfall has been shown to be the main cause of elevated nutrient pollution in groundwater beneath landfills. However, groundwater monitoring is often based on predetermined schedules without ...considering rainfall patterns. This study examined how rainfall patterns affect fluctuations in groundwater quality at the Coastal Park landfill in Cape Town, South Africa, and the relevance of current groundwater sampling schedules. Boreholes upstream and downstream of two large waste cells, one lined and the other unlined, were monitored for 15 weeks during the onset of the rainy season to detect changes in the groundwater level, pH, conductivity, dissolved oxygen, ammonia, nitrate, and phosphate. Rainfall patterns strongly affected the groundwater parameters, with widely varying fluctuation patterns and lag times. Conductivity peaked downstream of the lined cell 10 weeks later than at the unlined cell, with widely different fluctuation patterns (R2 = 0.36). Ammonia peaked downstream of both the unlined and lined cells well before the early rains, with very similar fluctuation patterns (R2 = 0.97), although it peaked 6 times higher in the unlined cell. Nitrate peaked at Weeks 2 to 4 downstream of the unlined and the lined cell, with a weak correlation (R2 = 0.56). A shorter nitrate peak and a net decrease throughout the rainy season were observed downstream of the lined cell. Phosphate showed a brief, multi-fold increase at Week 3 downstream of both the unlined and lined cells, displaying pH-induced mobilisation and a very strong correlation (R2 = 0.99) between these locations. Lag times and fluctuation patterns varied depending on the presence of liners, and rainfall patterns. Therefore, the low frequency sampling required by many South African landfill waste management permits and licences cannot identify pollutant peak concentrations or describe their trends, and high frequency sampling should be considered.
The Post-Operative Radiation Therapy in Endometrial Carcinoma (PORTEC)-4a trial is a randomized trial for women with high-intermediate risk endometrial cancer (EC), comparing individualized adjuvant ...treatment based on a molecular-integrated risk profile to standard adjuvant treatment; vaginal brachytherapy. To evaluate patient acceptability and pathology logistics of determining the risk profile, a pilot phase was included in the study.
PORTEC-4a is ongoing and the first 50 patients enrolled were included in the pilot phase. Primary endpoints of the pilot phase were patient acceptance, evaluated by analyzing the screening logs of the participating centers, and logistical feasibility of determination of the risk profile within 2 weeks, evaluated by analyzing the pathology database.
In the first year, 145 eligible women were informed about the trial at 13 centers, of whom 50 (35%) provided informed consent. Patient accrual ranged from 0 to 57% per center. Most common reasons for not participating were: not willing to participate in any trial (43.2%) and not willing to risk receiving no adjuvant treatment (32.6%). Analysis of the pathology database showed an average time between randomization and determination of the molecular-integrated risk profile of 10.2 days (1–23 days). In 5 of the 32 patients (15.6%), pathology review took >2 weeks.
The PORTEC-4a trial design was proven feasible with a satisfactory patient acceptance rate and an optimized workflow of the determination of the molecular-integrated risk profile. PORTEC-4a is the first randomized trial to investigate use of a molecular-integrated risk profile to determine adjuvant treatment in EC.
•Molecular-integrated risk profiling holds promise to improve individualization of treatment in endometrial cancer (EC).•PORTEC-4a is the first randomized clinical trial investigating molecular profile-based adjuvant treatment in EC.•The trial design was proven feasible with a good patient acceptance rate and logistical feasibility; accrual is ongoing.
Highlights • NPY acts at Y1 receptors in the dorsal horn to decrease inflammatory hyperalgesia. • NPY inhibits substance P release from primary afferent neurons. • Y1 is broadly co-expressed with ...CGRP in DRG neurons. • Inflammation increases coupling between Y1 receptors and G-proteins in the dorsal horn of the spinal cord. • Inflammation enhances NPY-Y1 mediated inhibition of substance P release and hyperalgesia.
This paper discusses the potential use of ‘managed aquifer recharge’ (MAR) in Cape Town to provide additional water supplies to the city that are fit-for-purpose. The paper investigates the ...feasibility of implementing MAR by simulating the artificial recharge of winter stormwater into the Cape Flats Aquifer (CFA), an extensive sandy, unconfined aquifer that covers most of metropolitan Cape Town’s urban landscape. The objective is to assess the storage capacity and supply potential of two MAR sites by modelling various scenarios in order to determine the feasibility of MAR as a viable strategy for achieving improved water security by augmenting groundwater water supply. The selected scenarios demonstrated that MAR could be used to minimise the risk of seawater intrusion and maximise the amount of water available for abstraction from the CFA. Six MAR scenarios provided strong evidence to suggest that there is sufficient storage capacity within the CFA for using stormwater to improve the wellfield yield in two regions of the CFA and which can sustainably yield approximately 18 Mm3 per year. The study concluded that the use of stormwater or treated wastewater could be deliberately used to recharge the CFA and as a viable option in support of the City of Cape Town’s intention to establish a water-resilient city by 2030.
Opioid receptor antagonists increase hyperalgesia in humans and animals, which indicates that endogenous activation of opioid receptors provides relief from acute pain; however, the mechanisms of ...long-term opioid inhibition of pathological pain have remained elusive. We found that tissue injury produced μ-opioid receptor (MOR) constitutive activity (MORCA) that repressed spinal nociceptive signaling for months. Pharmacological blockade during the posthyperalgesia state with MOR inverse agonists reinstated central pain sensitization and precipitated hallmarks of opioid withdrawal (including adenosine 3',5'-monophosphate overshoot and hyperalgesia) that required N-methyl-D-aspartate receptor activation of adenylyl cyclase type 1. Thus, MOR CA initiates both analgesic signaling and a compensatory opponent process that generates endogenous opioid dependence. Tonic MOR CA suppression of withdrawal hyperalgesia may prevent the transition from acute to chronic pain.
Recent studies suggest that targeting transcriptional machinery can lead to potent and selective anticancer effects in cancers dependent on high and constant expression of certain transcription ...factors for growth and survival. Cyclin-dependent kinase 7 (CDK7) is the catalytic subunit of the CDK-activating kinase complex. Its function is required for both cell-cycle regulation and transcriptional control of gene expression. CDK7 has recently emerged as an attractive cancer target because its inhibition leads to decreased transcript levels of oncogenic transcription factors, especially those associated with super-enhancers. Here, we describe a selective CDK7 inhibitor SY-1365, which is currently in clinical trials in populations of patients with ovarian and breast cancer (NCT03134638).
, SY-1365 inhibited cell growth of many different cancer types at nanomolar concentrations. SY-1365 treatment decreased MCL1 protein levels, and cancer cells with low BCL2L1 (BCL-XL) expression were found to be more sensitive to SY-1365. Transcriptional changes in acute myeloid leukemia (AML) cell lines were distinct from those following treatment with other transcriptional inhibitors. SY-1365 demonstrated substantial antitumor effects in multiple AML xenograft models as a single agent; SY-1365-induced growth inhibition was enhanced in combination with the BCL2 inhibitor venetoclax. Antitumor activity was also observed in xenograft models of ovarian cancer, suggesting the potential for exploring SY-1365 in the clinic in both hematologic and solid tumors. Our findings support targeting CDK7 as a new approach for treating transcriptionally addicted cancers. SIGNIFICANCE: These findings demonstrate the molecular mechanism of action and potent antitumor activity of SY-1365, the first selective CDK7 inhibitor to enter clinical investigation.
In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose ...of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose.
Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district.
Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.
PDF
