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Hydrological prediction in ungauged basins based on spatiotemporal characteristics

Hydrological prediction in ungauged basins often relies on the parameter transplant method, which incurs high labor costs due to its dependence on expert input. To address these issues, we propose a novel hydrological prediction model named STH-Trans, which leverages multiple spatiotemporal views to enhance its predictive capabilities. Firstly, we utilize existing geographic and topographic indicators to identify and select watersheds that exhibit similarities. Subsequently, we establish an initial regression model using the TrAdaBoost algorithm based on the hydrologic data from the selected watershed stations. Finally, we refine the initial model by incorporating multiple spatiotemporal views, employing semi-supervised learning to create the STH-Trans model. The results of our experiments underscore the efficiency of the STH-Trans model in predicting runoff for ungauged basins. This innovation leads to a substantial increase in model accuracy ranging from 7.9% to 30% compared to various conventional methods. The model not only offers data support for water resource management, flood mitigation, and disaster relief efforts, but also provides decision support for hydrologists.

Adjuvant Nivolumab for Localized Renal Cell Carcinoma at High Risk of Recurrence After Nephrectomy: Part B of the Randomized, Placebo-Controlled, Phase III CheckMate 914 Trial

PURPOSE CheckMate 914 is a two-part, randomized phase III trial evaluating adjuvant nivolumab plus ipilimumab (part A) or adjuvant nivolumab monotherapy (part B) versus placebo in mutually exclusive populations of patients with localized renal cell carcinoma (RCC) at high risk of postnephrectomy recurrence. Part A showed no disease-free survival (DFS) benefit for adjuvant nivolumab plus ipilimumab versus placebo. We report results from part B. METHODS Patients were randomly assigned (2:1:1) to nivolumab (240 mg once every 2 weeks for up to 12 doses), placebo, or nivolumab (240 mg once every 2 weeks for up to 12 doses) plus ipilimumab (1 mg/kg once every 6 weeks for up to four doses). The planned treatment duration was 24 weeks (approximately 5.5 months). The primary end point was DFS per blinded independent central review (BICR) for nivolumab versus placebo; safety was a secondary end point. RESULTS Overall, 825 patients were randomly assigned to nivolumab (n = 411), placebo (n = 208), or nivolumab plus ipilimumab (n = 206). With a median follow-up of 27.0 months (range, 18.0-42.4), the primary end point of improved DFS per BICR with nivolumab versus placebo was not met (hazard ratio [HR], 0.87 [95% CI, 0.62 to 1.21]; P = .40); the median DFS was not reached in either arm, and 18-month DFS rates were 78.4% versus 75.4%. The HR for DFS per investigator was 0.80 (95% CI, 0.58 to 1.12; P = .19). Grade 3-4 all-cause adverse events (AEs) occurred in 17.2%, 15.0%, and 28.9% of patients with nivolumab, placebo, and nivolumab plus ipilimumab, respectively. Any-grade treatment-related AEs led to discontinuation in 9.6%, 1.0%, and 28.4%, respectively. CONCLUSION Part B of CheckMate 914 did not meet the primary end point of improved DFS for nivolumab versus placebo in patients with localized RCC at high risk of postnephrectomy recurrence.

First report of a major management target species, chironomid Paratanytarsus grimmii (Diptera: Chironomidae) larvae, in drinking water treatment plants (DWTPs) in South Korea

Ensuring the supply of safe and high-quality drinking water can be compromised by the presence of chironomid larvae in drinking water treatment plants (DWTPs), which may contaminate municipal water systems through freshwater resources. Chironomids are dominant species known for their resilience to a broad range of extreme aquatic environments. This study aimed to identify the morphological characteristics and obtain genetic information of the chironomid Paratanytarsus grimmii found in the water intake source and freshwater resource of DWTPs in Korea, highlighting the potential possibility of a parthenogenetic chironomid outbreak within DWTP networks. The distribution of chironomid larvae at the water intake source site (DY) of the Danyang DWTP and the freshwater resource (ND) of the Nakdong River was investigated. A total of 180 chironomid individuals, encompassing three subfamilies and six species from six 6 genera were identified at the DY site, with Procladius nigriventris being the dominant species. At the ND site, fifty chironomid individuals, encompassing two subfamilies and six species from six genera, were identified, with Cricotopus sylvestris being the dominant species. The morphological characteristics of the head capsule, mentum, mandible, and antennae of six P. grimmii larvae collected from the DY and ND sites were characterized. DNA barcoding and phylogenetic analysis revealed distinct mitochondrial diversities between the P. grimmii larvae from DY and those from ND. These results provide crucial information for the morphological identification and DNA barcoding of the key management target chironomid P. grimmii larvae, which can be used to detect the occurrence of this chironomid species in DWTPs.

Reply to C. Fuchao et al

Protocol for extracting flow hydrograph shape metrics for use in time-series flood hydrology analysis

The shape characteristics of flow hydrographs hold essential information for understanding, monitoring and assessing changes in flow and flood hydrology at reach and catchment scales. However, the analysis of individual hydrographs is time consuming, making the analysis of hundreds or thousands of them unachievable. A method or protocol is needed to ensure that the datasets being generated, and the metrics produced, have been consistently derived and validated. In this lab protocol, we present workflows in Python for extracting flow hydrographs with any available temporal resolution from any Open Access or publicly available gauging station records. The workflow identifies morphologically-defined flow and flood types (i.e. in-channel fresh, high flow and overbank flood) and uses them to classify hydrographs. It then calculates several at-a-station and upstream-to-downstream hydrograph shape metrics including kurtosis, skewness, peak hydrograph stage, peak arrival time, rate-of-rise, peak-to-peak travel time, flood wave celerity, flood peak attenuation, and flood wave attenuation index. Some metrics require GIS-derived data, such as catchment area and upstream-to-downstream channel distance between gauges. The output dataset provides quantified hydrograph shape metrics which can be used to track changes in flow and flood hydrographs over time, or to characterise the flow and flood hydrology of catchments and regions. The workflows are flexible enough to allow for additional hydrograph shape indicators to be added or swapped out, or to use a different hydrograph classification method that suits local conditions. The protocol could be considered a change detection tool to identify where changes in hydrology are occurring and where to target more sophisticated modelling exercises to explain the changes detected. We demonstrate the workflow using 117 Open Access gauging station records that are available for coastal rivers of New South Wales (NSW), Australia.

<i>TERT</i> Expression and Clinical Outcome in Pulmonary Carcinoids

PURPOSE The clinical course of pulmonary carcinoids ranges from indolent to fatal disease, suggesting that specific molecular alterations drive progression toward the fully malignant state. A similar spectrum of clinical phenotypes occurs in pediatric neuroblastoma, in which activation of telomerase reverse transcriptase ( TERT ) is decisive in determining the course of disease. We therefore investigated whether TERT expression defines the clinical fate of patients with pulmonary carcinoid. METHODS TERT expression was examined by RNA sequencing in a test cohort and a validation cohort of pulmonary carcinoids (n = 88 and n = 105, respectively). A natural TERT expression cutoff was determined in the test cohort on the basis of the distribution of TERT expression, and its prognostic value was assessed by Kaplan-Meier survival estimates and multivariable analyses. Telomerase activity was validated by telomere repeat amplification protocol assay. RESULTS Similar to neuroblastoma, TERT expression exhibited a bimodal distribution in pulmonary carcinoids, separating tumors into TERT -high and TERT- low subgroups. A natural TERT cutoff discriminated unfavorable from favorable clinical courses with high accuracy both in the test cohort (5-year overall survival [OS], 0.547 ± 0.132 v 1.0; P &lt; .001) and the validation cohort (5-year OS, 0.788 ± 0.063 v 0.913 ± 0.048; P &lt; .001). In line with these findings, telomerase activity was largely absent in TERT -low tumors, whereas it was readily detectable in TERT- high carcinoids. In multivariable analysis considering TERT expression, histology (typical v atypical carcinoid), and stage (≤IIA v ≥IIB), high TERT expression was an independent prognostic marker for poor survival, with a hazard ratio of 5.243 (95% CI, 1.943 to 14.148; P = .001). CONCLUSION Our data demonstrate that high TERT expression defines clinically aggressive pulmonary carcinoids with fatal outcome, similar to neuroblastoma, indicating that activation of TERT may be a defining feature of lethal cancers.

The impact of de-familization on green innovation: Evidence from SRDI family firms in China

Green innovation is essential for sustainable development, especially in China’s Specialized-Refined-Differentiated-Innovative (SRDI) enterprises. Family-owned SRDI firms, in particular, have attracted attention due to their de-familization strategies and their influence on green innovation. Our study analyzes panel data from 2016 to 2021 for listed SRDI family firms to investigate how de-familization in management rights and ownership impacts green innovation. Using socio-emotional wealth (SEW) theory and a fixed-effects model, we find that de-familization significantly negatively affects green innovation, with corporate governance serving as a mediating factor. Digital transformation moderates these negative effects, while market concentration exacerbates them. These impacts are more pronounced in firms before being designated as "Little Giants," those receiving higher government subsidies, those located in eastern regions, or those not classified as major polluters. This research provides actionable insights for SRDI family firms to strategically manage de-familization, optimize resource allocation, implement customized governance strategies, and promote sustainable growth.

Phase III Evaluation of Treatment Combinations in Three-Arm Trials

Phase III trials that randomly assign patients to a control treatment (C), an experimental treatment (A), or a combination treatment (AB) should be designed with the goal to recommend the best treatment: AB (if it is better than A and C), A (if it is better than C, and AB is not better than A), or C (if neither AB nor A is better than C). However, this goal can be challenging to achieve with statistical confidence. We performed a survey of cancer trials published in five journals from January 2018 to May 2024 to assess the trial designs being used in this setting and found that three quarters of them did not have a provision for a formal comparison of the AB treatment arm with the A treatment arm, a possible shortcoming. A limited simulation evaluates two analysis strategies that incorporate an AB versus A comparison and is used to formulate some recommendations for designing these types of trials.

Measuring women’s empowerment in aquaculture in northwestern Bangladesh using a project level women’s empowerment in fisheries index (pro-WEFI)

Gender equality and women’s empowerment have been increasingly emphasised in food production systems, including fisheries and aquaculture. Accurate assessment and understanding of the state, progress and changes in women’s empowerment in the sub-sectors is required. We applied the project level Women’s Empowerment in Fisheries and Aquaculture Index (pro-WEFI), which is based on the project-level women’s empowerment in agriculture index (pro-WEAI) to standardize the measurement of women’s agency and empowerment in fisheries and aquaculture. Drawing on a survey conducted in north-western Bangladesh, we examined quantitative pro-WEFI data collected from 217 households engaged in aquaculture. Only 33% of the women and 48% of the men in the sample achieved empowerment in aquaculture, attaining scores of 0.75 and above. The mean disempowerment score (1-3DE) revealed that both women and men failed to achieve adequacy on average in nearly 28% of the indicators. Nearly 40% of the dual adult households did not attain gender parity with women achieving lower adequacy scores than men from the same household. Women’s disempowerment was primarily driven by lack of autonomy in their use of income (18.5%), inability to visit important locations (17.4%), and inadequate access to and decision making on financial services (13.4%). Our findings emphasize the significance of conducting comprehensive assessments of women’s empowerment in aquaculture initiatives and its various domains and indicators inform the development of targeted and effective interventions. By identifying domains where gender inequality is most pronounced, projects can better design interventions to create targeted impacts in critical areas.

Will Prolyl Hydroxylase Inhibitors Supplant Erythropoiesis-Stimulating Agents and IV Iron in the Treatment of Chemotherapy-Induced Anemia?

Enhancing semantical text understanding with fine-tuned large language models: A case study on Quora Question Pair duplicate identification

Semantical text understanding holds significant importance in natural language processing (NLP). Numerous datasets, such as Quora Question Pairs (QQP), have been devised for this purpose. In our previous study, we developed a Siamese Convolutional Neural Network (S-CNN) that achieved an F1 score of 82.02% (95% C.I.: 81.83%-82.20%). Given the growing attention toward large language models (LLMs) like ChatGPT, we aimed to explore their effectiveness in text similarity tasks. In this research, we leveraged 5 pretrained LLMs, conducted various fine-tuning approaches (prompt engineering, n-shot learning, and supervised learning using the low-rank adaptation [LoRA]), and compared their performance using F1 score. To ensure a fair comparison, we followed our previous study’s design and dataset by employing a 10-fold cross-validation for supervised model training and evaluation. Additionally, we conducted a secondary study by introducing a recent larger LLM with 70B parameters and comparing it with the 7B model using the GLUE benchmark, and both models were finetuned with the corpus. The fine-tuned LLaMA model with 7B parameters (qLLaMA_LoRA-7B) using 100,000 QQP corpus yielded the best results, achieving an F1 score of 84.9% (95% C.I.: 84.13%-85.67%), which outperformed the Alpaca_LoRA-65B (finetuned based on LLaMA-65B) (F1: 64.98% [64.72%-65.25%]; P&lt;0.01) and had a 3% improvement compared to our previously published best model, S-CNN. The finetuned LLaMA3.1-70B (qLLaMA3.1_LoRA-70B) with 70B parameters (F1: 74.4%) outperformed the qLLaMA_LoRA-7B (F1: 71.9%) using the GLUE benchmark. The study demonstrated an effective LLM finetuning framework, which highlights the importance of finetuning LLMs for improved performance. Our task-specific supervised finetuning demonstrated improved LLM performance compared to larger pretrained models with or without n-shot learning; moreover, finetuning a larger LLM further improved performance compared to finetuning a smaller LLM. Our LLM-based finetuning framework may potentially improve various document similarity tasks, such as matching resumes with job descriptions, recommending subject-matter experts, or identifying potential reviewers for grant proposals or manuscript submissions.

Dual Immune Checkpoint Inhibition in Melanoma and PD-L1 Expression: The Jury Is Still Out

This comment discusses the use of PD-L1 as a biomarker to guide treatment decisions for metastatic melanoma.

Impact of capacity building through learning, training, and coaching on agricultural innovation

Successful innovation requires employees to have intellectual and technical capacity. This study explored the effects of capacity building through educational learning, organizational training, and coaching on agricultural innovation. A sample of 142 operational-level agriculture scientists working within a public sector agricultural research organisation in Zimbabwe. Six key informants were also consulted. Descriptive statistics, factor analysis, principal component analysis (PCA), correlation analysis, and binary logistic regression analysis were employed. Results showed significant positive relationships between the variables stating that operational scientists receive adequate academic study opportunities from the research organisation and the one stating that they have relevant academic qualifications to help drive agriculture innovation (r = 0.421***). This reflects that once capacitated through educational learning, the employees gain the confidence and ability to innovate, which could be attributed to improved intelligence quotient (IQ). A significant positive relationship was also observed between the variables, stating that research employees required further training and that improving training would significantly improve innovation (r = 0.47***). Lastly, the variables, stating that direct supervisors offer adequate guidance to stimulate innovation positively correlated to the one stating that coaching has helped improve the operational staff’s innovativeness (P = 0.493***). This implies that efforts being put in by supervisors significantly contribute to innovation. Budgetary constraints were the leading challenge mentioned by 90.1% of the sample. Notably, there is a critical need to improve physical training workshops, exposure visits, and short courses to enhance innovativeness, as revealed by more than 70% of the respondents. The study also suggests cost-effective strategies to enhance capacity building and consequently stimulate innovation.

Sexual Health and Quality of Life in Patients With Low-Risk Early-Stage Cervical Cancer: Results From GCIG/CCTG CX.5/SHAPE Trial Comparing Simple Versus Radical Hysterectomy

PURPOSE Simple hysterectomy and pelvic node assessment (SHAPE) is a phase III randomized trial (ClinicalTrials.gov identifier: NCT01658930 ) reporting noninferiority of simple compared with radical hysterectomy for oncologic outcomes in low-risk cervical cancer. This study presents secondary outcomes of sexual health and quality of life (QOL) of the SHAPE trial. METHODS Participants were randomly assigned to receive either radical or simple hysterectomy. Sexual health was assessed up to 36 months postoperatively using the Female Sexual Function Index (FSFI) and Female Sexual Distress Scale-Revised and QOL using European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Cervical Cancer-Specific Module (QLQ-CX24) questionnaires. RESULTS Among participants with at least one QOL measure, clinical and pathologic characteristics were balanced and with no differences in preoperative baseline scores for sexual health or QOL between groups. FSFI total score met the cutoff for dysfunction up to 6 months ( P = .02) in the radical hysterectomy group. Group differences favored simple hysterectomy for FSFI subscales: desire and arousal at 3 months ( P ≤ .001) and pain and lubrication up to 12 months ( P ≤ .018). Both groups met the cutoff for sexual distress but was higher in radical hysterectomy at 3 months ( P = .018). For QLQ-CX24, symptom experience was significantly better up to 24 months ( P = .031) and body image better at 3, 24, and 36 months ( P ≤ .01) for simple hysterectomy. Sexual-vaginal functioning was significantly better up to 24 months ( P ≤ .022) and more sexual activity up to 36 months ( P = .024) in the simple hysterectomy arm. Global health status was significantly higher at 36 months for simple hysterectomy ( P = .025). CONCLUSION Simple hysterectomy was associated with lower rates of sexual dysfunction than radical hysterectomy, with a lower proportion of women having sustained sexual-vaginal dysfunction. These results further support the benefit of surgical de-escalation for low-risk cervical cancer.

FRESH extrusion 3D printing of type-1 collagen hydrogels photocrosslinked using ruthenium

The extrusion bioprinting of collagen material has many applications relevant to tissue engineering and regenerative medicine. Freeform Reversible Embedding of Suspended Hydrogels (FRESH) technology is capable of 3D printing collagen material with the specifications and details needed for precise tissue guidance, a crucial requirement for effective tissue repair. While FRESH has shown repeated success and reliability for extrusion printing, the mechanical properties of completed collagen prints can be improved further by post-print crosslinking methodologies. Photoinitiator-based crosslinking methods are simple and have proven effective in strengthening protein-based materials. The ruthenium and sodium persulfate photoinitiator system (Ru(bpy)3/SPS) has been suggested as an effective crosslinking method for collagen materials. Herein, we describe the procedure our group has developed to combine extrusion-based 3D printing of type-1 collagen using FRESH technology with Ru(bpy)3/SPS photoinitiated crosslinking methods to improve the strength and stability of 3D printed collagen structures. Mechanical testing and cell biocompatibility assessments were performed to investigate the impact of Ru(bpy)3/SPS photoinitiated crosslinking and highlight the potential limitations of this method. These results demonstrate a significant improvement in the compressive strength of type-1 collagen samples as the Ru(bpy)3/SPS concentration increases. Additionally, type-1 collagen samples crosslinked with up to 1/10 mM Ru(bpy)3/SPS support PC12 cell viability over a period of 7 days. The primary limitations that were observed and described in detail in this protocol are: the FRESH slurry preparation, printing environment, extrusion printer hardware, and quality of the ruthenium reagent.

Incidence of Medication-Related Osteonecrosis of the Jaw in Patients With Breast Cancer During a 20-Year Follow-Up: A Population-Based Multicenter Retrospective Study

PURPOSE Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of antiresorptive therapy, which is standard practice for patients with breast cancer and bone metastases. However, the population-based incidence of MRONJ is not well established. We therefore performed a retrospective multicenter study to assess the incidence for a whole Austrian federal state (Tyrol). MATERIALS AND METHODS This retrospective multicenter study was conducted between 2000 and 2020 at all nine breast centers across Tyrol, Austria. Using the cancer registry, the total Tyrolean population was screened for all patients with breast cancer. All patients with breast cancer and bone metastases receiving antiresorptive therapy were finally included in the study. RESULTS From 8,860 patients initially screened, 639 individuals were eligible and included in our study. Patients received antiresorptive therapy once per month without de-escalation of therapy. MRONJ was diagnosed in 56 (8.8%, 95% CI, 6.6 to 11.0) patients. The incidence of MRONJ was 11.6% (95% CI, 8.0 to 15.3) in individuals treated with denosumab only, 2.8% (95% CI, 0.7 to 4.8) in those treated with bisphosphonates only, and 16.3% (95% CI, 8.8 to 23.9) in the group receiving bisphosphonates followed by denosumab. Individuals developed MRONJ significantly earlier when treated with denosumab. Time to MRONJ after treatment initiation was 4.6 years for individuals treated with denosumab only, 5.1 years for individuals treated with bisphosphonates only, and 8.4 years for individuals treated with both consecutively. CONCLUSION MRONJ incidence in breast cancer patients with bone metastases was found to be considerably higher, especially for patients receiving denosumab, when compared with available data in the literature. Additionally, patients treated with denosumab developed MRONJ significantly earlier.

Synthesising enablers and barriers to hepatocellular carcinoma surveillance—A systematic review of qualitative findings

Background &amp; aims This systematic literature review of qualitative findings aims to identify the perceived barriers and enablers for hepatocellular carcinoma (HCC) surveillance from patient and clinician perspectives. Methods A systematic search of databases using key term combinations with the following inclusion criteria: 1) qualitative and quantitative (survey) studies exploring barriers and enablers of HCC surveillance, and 2) qualitative and quantitative (survey) studies exploring barriers and enablers of enagagement in clinical care for patients with cirrhosis and/or viral hepatitis. Results The search returned 445 citations: 371 did not meet the study criteria and were excluded. 74 studies proceeded to full-text review, leading to 21 included studies (15 studies from searching with a further six studies from citation review) progressing to data extraction by two independent reviewers. Results from studies exploring patients’ perspectives reinforce that barriers are experienced by patients across different health settings, cultures, and regions. Logistical barriers including costs and transportation, and knowledge/awareness barriers were commonly identified. Studies that included clinician perspectives highlighted the need for healthcare provider education and system-level interventions to optimize HCC surveillance uptake in clinical practice. Conclusion These findings highlight the critical need for interventions that enable engagement in HCC surveillance in health services.

Antibiotic consumption and utilization at a large tertiary care level hospital in Uganda: A point prevalence survey

Introduction Effective antimicrobial stewardship programs require data on antimicrobial consumption (AMC) and utilization (AMU) to guide interventions. However, such data is often scarce in low-resource settings. We describe the consumption and utilization of antibiotics at a large tertiary-level hospital in Uganda. Methods In this cross-sectional study at Kiruddu National Referral Hospital, we analyzed medicine delivery records for the period July 2021 to June 2022, accessed on 12/08/2022, to extract AMC data expressed as defined daily doses (DDDs) per 1000 inhabitants per day (DID). We used the WHO point prevalence survey (PPS) to analyze AMU data with a systematic sampling of outpatient department (OPD) for a period between June and August 2022 and selected all inpatient department (IPD) patients admitted before 8:00 AM on 27/11/2022. AMU data was analyzed as the proportion of individual antibiotic prescriptions, indications for prescriptions, and compliance with the national treatment guidelines. Both AMC and AMU data were categorized by the WHO AWaRe (access, watch, and reserve) criteria. Results In the year 2021–2022, a total of 6.05 DID of antibiotics were consumed comprising 3.61 DID (59.6%) access, 2.44 DID (40.3%) watch, and 0.003 (0.1%) reserve antibiotics. The most consumed antibiotics comprised penicillin (1.61 DID, 26.7%), cephalosporins (1.51, 25%), and imidazole (1.10 DID, 18.1%). A total of 119/211 (56%) patients in the OPD and 99/172 (57.5%) patients in the IPD were prescribed antibiotics. Of the 158 OPD antibiotic prescriptions, 73 (46.2%) were access, 72 (45.6%) were watch, 0 (0%) were reserve, and 13 (8.2%) were unclassified antibiotics. Of the 162 IPD antibiotic prescriptions, 62 (38.3%) were access, 88 (54.3%) were watch, 01 (0.6%) was reserve, and 11 (6.8%) were unclassified antibiotics. Indications for antibiotic prescriptions in the OPD comprised respiratory tract infections (53, 38.1%), urinary tract infections (34, 26.6%), gastrointestinal infections (20, 14.4%), sepsis (17, 12.2%), and medical prophylaxis (12, 8.7%). The indications for antibiotic prescriptions in the IPD comprised sepsis (28.2%), respiratory tract infections (18.3%), burn wounds (14.1%), and gastrointestinal infections (14.1%). Conclusion Prescription of watch antibiotics in both OPD and IPD hospital settings was high. Establishment of robust antimicrobial stewardship measures could help improve the rational prescription of antibiotics.

Measuring social, economic, policy, and health system determinants of maternal health and survival: An urgent global priority

In 2015, the World Health Organization (WHO) released global targets and strategies for reducing maternal mortality in the Sustainable Development Goal (SDG) period developed through broad stakeholder consultations. The targets and strategies identified in the “Strategies toward Ending Preventable Maternal Mortality (EPMM)” report are grounded in a systemic and human rights approach to maternal health and aim to address the broad spectrum of key social, political, economic, and health system determinants of maternal health and survival, as exemplified by 11 Key Themes. These upstream determinants of maternal survival are not well represented in maternal health measurement efforts, which tend to focus on service delivery. Thus, work was undertaken to develop a core set of maternal health indicators that could drive progress toward achieving the recommendations laid out in the EPMM Strategies that identified a menu of 25 indicators and 7 standard stratifiers related to the legal and policy environment, accountability mechanisms, inequities in access and quality, and empowerment of women, girls, families, and communities. Measurement experts have called for more research to ensure that indicators for monitoring maternal health, including its upstream determinants, are valid, which is critical if such measures are to be effective for driving and tracking progress toward ending preventable maternal deaths. This paper describes nine research reports emanating from seven discrete research studies to validate ten indicators in India, Ghana and Argentina that are compiled in a PLOS Collection with the aim of illustrating the breadth of the validation work, extracting some unifying themes and common findings, and discussing the implications for policy and practice they suggest.

Anatomical variations in Eurasian wolf (Canis lupus lupus) (Carnivora: Canidae) of the salivary glands: A histological and histochemical investigation

The study involved a gross anatomical description of the parotid gland, mandibular gland, monostomatic sublingual gland, polystomatic sublingual gland, and zygomatic gland in 12 adult Eurasian wolves (Canis lupus lupus) (wild free-ranging individuals and their zoo counterparts), including their morphometry and microscopic evaluation using hematoxylin &amp; eosin, mucicarmine, azan trichrome, PAS, AB pH 1.0, AB pH 2.5; AB pH 2.5/PAS, and HDI stainings. Topographically, the salivary glands were located similarly to those of other terrestrial Carnivora. The parotid gland in all wolves had a shape similar to a trapezoid (four angles). The parotid duct opened onto the fourth upper premolar (P4). The parotid gland was a branched alveolar complex that produced serous secretion. In captive specimens, the mandibular gland was a complex branched tubular gland producing mucous secretion, while in free-ranging wolves it was a branched tubuloalveolar gland producing mucoserous secretion. The monostomatic sublingual gland in free-ranging wolves was a complex branched tubuloalveolar gland that produced seromucous secretion, while in captive wolves, it revealed a mucoserous secretion character. The polystomatic sublingual gland consisted of several independent packets (from 6–7 to 7–8) and was a complex branched tubuloalveolar gland with seromucous secretion. The zygomatic duct opened onto the last upper molar tooth (M3), and this gland was a complex branched tubular gland producing mucous secretion. The anatomical and histological similarities between the salivary glands of the oral cavity in captive and free-ranging wolves, compared to other terrestrial carnivores, provide valuable insights for veterinary treatments and understanding pathological conditions. These findings emphasize the need for further research on diverse populations of wolves and related species within the Canidae family to better understand the influence of diet on salivary gland morphology.