River Leven catchment initiative: synthesis of current knowledge to help identify environmental management priorities to improve the water environment

The study addressed six main research questions. 1. What is the current condition of all rivers, lochs and ground waters in the River Leven catchment, based on available information? 2. What are the main pressures on the aquatic environment and the sources of those pressures? 3. What are the environmental management priorities for improving the water environment? 4. What is the baseline socio-economic condition of the River Leven catchment? 5. What is the current condition of Loch Leven and its catchment, and how have improvements supported socio-economic development? 6. What are the gaps in evidence and how can they be addressed? The output from this project provides a “first-pass” assessment of our understanding of the River Leven catchment. It is not intended to be a comprehensive review of all of the data and information available. Draft environmental priorities are suggested for further consideration

Maintenance of Sertoli Cell Number and Function in Immature Human Testicular Tissues Exposed to Platinum-Based Chemotherapy-Implications for Fertility Restoration

Background: Retrospective studies in adult survivors of childhood cancer show long-term impacts of exposure to alkylating chemotherapy on future fertility. We recently demonstrated germ cell loss in immature human testicular tissues following exposure to platinum-based chemotherapeutic drugs. This study investigated the effects of platinum-based chemotherapy exposure on the somatic Sertoli cell population in human fetal and pre-pubertal testicular tissues. Methods: Human fetal (n = 23; 14–22 gestational weeks) testicular tissue pieces were exposed to cisplatin (0.5 or 1.0 μg/ml) or vehicle for 24 h in vitro and analysed 24–240 h post-exposure or 12 weeks after xenografting. Human pre-pubertal (n = 10; 1–12 years) testicular tissue pieces were exposed to cisplatin (0.5 μg/ml), carboplatin (5 μg/ml) or vehicle for 24 h in vitro and analysed 24–240 h post-exposure; exposure to carboplatin at 10-times the concentration of cisplatin reflects the relative clinical doses given to patients. Immunohistochemistry was performed for SOX9 and anti-Müllerian hormone (AMH) expression and quantification was carried out to assess effects on Sertoli cell number and function respectively. AMH and inhibin B was measured in culture medium collected post-exposure to assess effects on Sertoli cell function. Results: Sertoli cell (SOX9(+ve)) number was maintained in cisplatin-exposed human fetal testicular tissues (7,647 ± 459 vs. 7,767 ± 498 cells/mm(2); p > 0.05) at 240 h post-exposure. No effect on inhibin B (indicator of Sertoli cell function) production was observed at 96 h after cisplatin (0.5 and 1.0 μg/ml) exposure compared to control (21 ± 5 (0.5 μg/ml cisplatin) vs. 23 ± 7 (1.0 μg/ml cisplatin) vs. 25 ± 7 (control) ng/ml, p > 0.05). Xenografting of cisplatin-exposed (0.5 μg/ml) human fetal testicular tissues had no long-term effect on Sertoli cell number or function (percentage seminiferous area stained for SOX9 and AMH, respectively), compared with non-exposed tissues. Sertoli cell number was maintained in human pre-pubertal testicular tissues following exposure to either 0.5 μg/ml cisplatin (6,723 ± 1,647 cells/mm(2)) or 5 μg/ml carboplatin (7,502 ± 627 cells/mm(2)) compared to control (6,592 ± 1,545 cells/mm(2)). Conclusions: This study demonstrates maintenance of Sertoli cell number and function in immature human testicular tissues exposed to platinum-based chemotherapeutic agents. The maintenance of a functional Sertoli cell environment following chemotherapy exposure suggests that fertility restoration by spermatogonial stem cell (SSC) transplant may be possible in boys facing platinum-based cancer treatment

Cisplatin and carboplatin result in similar gonadotoxicity in immature human testis with implications for fertility preservation in childhood cancer

Background Clinical studies indicate chemotherapy agents used in childhood cancer treatment regimens may impact future fertility. However, effects of individual agents on prepubertal human testis, necessary to identify later risk, have not been determined. The study aimed to investigate the impact of cisplatin, commonly used in childhood cancer, on immature (foetal and prepubertal) human testicular tissues. Comparison was made with carboplatin, which is used as an alternative to cisplatin in order to reduce toxicity in healthy tissues. Methods We developed an organotypic culture system combined with xenografting to determine the effect of clinically-relevant exposure to platinum-based chemotherapeutics on human testis. Human foetal and prepubertal testicular tissues were cultured and exposed to cisplatin, carboplatin or vehicle for 24 h, followed by 24-240 h in culture or long-term xenografting. Survival, proliferation and apoptosis of prepubertal germ stem cell populations (gonocytes and spermatogonia), critical for sperm production in adulthood, were quantified. Results Cisplatin exposure resulted in a significant reduction in the total number of germ cells (- 44%, p <0.0001) in human foetal testis, which involved an initial loss of gonocytes followed by a significant reduction in spermatogonia. This coincided with a reduction (- 70%, p <0.05) in germ cell proliferation. Cisplatin exposure resulted in similar effects on total germ cell number (including spermatogonial stem cells) in prepubertal human testicular tissues, demonstrating direct relevance to childhood cancer patients. Xenografting of cisplatin-exposed human foetal testicular tissue demonstrated that germ cell loss (- 42%, p <0.01) persisted at 12 weeks. Comparison between exposures to human-relevant concentrations of cisplatin and carboplatin revealed a very similar degree of germ cell loss at 240 h post-exposure. Conclusions This is the first demonstration of direct effects of chemotherapy exposure on germ cell populations in human foetal and prepubertal testis, demonstrating platinum-induced loss of all germ cell populations, and similar effects of cisplatin or carboplatin. Furthermore, these experimental approaches can be used to determine the effects of established and novel cancer therapies on the developing testis that will inform fertility counselling and development of strategies to preserve fertility in children with cancer.Peer reviewe

Response of Herbicide-Resistant Palmer Amaranth ( Amaranthus palmeri

Palmer amaranth is a very problematic weed in several crops in the southern USA due to its competitive ability and resistance to herbicides representing different mechanisms of action. Variation in growth and subsequent interference of North Carolina Palmer amaranth accessions has not been examined. A greenhouse experiment determined response of 15 North Carolina Palmer amaranth accessions to drought stress beginning 15 days after seedling emergence (DAE) for a duration of 3, 5, 7, and 9 days. Following exposure to drought, plants were grown under optimal moisture conditions until harvest at 30 DAE. Five accessions each of glyphosate-resistant (GR), acetolactate synthase inhibitor-resistant (ALSR), and acetolactate synthase inhibitor-susceptible and glyphosate-susceptible (ALSS/GS) were compared. Variation in response to drought stress, based on height and dry weight reduction relative to nonstressed controls, was noted among accessions. Stress for 3 or more days affected height and dry weight. Height and dry weight of GR and ALSR accession groups were reduced less by drought than the ALSS/GS accession group. Results suggest a possible relationship between herbicide resistance and ability of Palmer amaranth to withstand drought stress and thus a possible competitive advantage for resistant accessions under limited moisture availability

Evaluation of effectiveness and safety of the CorPath GRX robotic system in endovascular embolization procedures of cerebral aneurysms.

BACKGROUND Robotic-assisted neurointervention was recently introduced, with implications that it could be used to treat neurovascular diseases. OBJECTIVE To evaluate the effectiveness and safety of the robotic-assisted platform CorPath GRX for treating cerebral aneurysms. METHODS This prospective, international, multicenter study enrolled patients with brain aneurysms that required endovascular coiling and/or stent-assisted coiling. The primary effectiveness endpoint was defined as successful completion of the robotic-assisted endovascular procedure without any unplanned conversion to manual treatment with guidewire or microcatheter navigation, embolization coil(s) or intracranial stent(s) deployment, or an inability to navigate vessel anatomy. The primary safety endpoint included intraprocedural and periprocedural events. RESULTS The study enrolled 117 patients (74.4% female) with mean age of 56.6 years from 10 international sites,. Headache was the most common presenting symptom in 40/117 (34.2%) subjects. Internal carotid artery was the most common location (34/122, 27.9%), and the mean aneurysm height and neck width were 5.7±2.6 mm and 3.5±1.4 mm, respectively. The overall procedure time was 117.3±47.3 min with 59.4±32.6 min robotic procedure time. Primary effectiveness was achieved in 110/117 (94%) subjects with seven subjects requiring conversion to manual for procedure completion. Only four primary safety events were recorded with two intraprocedural aneurysm ruptures and two strokes. A Raymond-Roy Classification Scale score of 1 was achieved in 71/110 (64.5%) subjects, and all subjects were discharged with a modified Rankin Scale score of ≤2. CONCLUSIONS This first-of-its-kind robotic-assisted neurovascular trial demonstrates the effectiveness and safety of the CorPath GRX System for endovascular embolization of cerebral aneurysm procedures. TRIAL REGISTRATION NUMBER NCT04236856

The implications of three major new trials for the effect of water, sanitation and hygiene on childhood diarrhea and stunting: a consensus statement

BACKGROUND: Three large new trials of unprecedented scale and cost, which included novel factorial designs, have found no effect of basic water, sanitation and hygiene (WASH) interventions on childhood stunting, and only mixed effects on childhood diarrhea. Arriving at the inception of the United Nations' Sustainable Development Goals, and the bold new target of safely managed water, sanitation and hygiene for all by 2030, these results warrant the attention of researchers, policy-makers and practitioners. MAIN BODY: Here we report the conclusions of an expert meeting convened by the World Health Organization and the Bill and Melinda Gates Foundation to discuss these findings, and present five key consensus messages as a basis for wider discussion and debate in the WASH and nutrition sectors. We judge these trials to have high internal validity, constituting good evidence that these specific interventions had no effect on childhood linear growth, and mixed effects on childhood diarrhea. These results suggest that, in settings such as these, more comprehensive or ambitious WASH interventions may be needed to achieve a major impact on child health. CONCLUSION: These results are important because such basic interventions are often deployed in low-income rural settings with the expectation of improving child health, although this is rarely the sole justification. Our view is that these three new trials do not show that WASH in general cannot influence child linear growth, but they do demonstrate that these specific interventions had no influence in settings where stunting remains an important public health challenge. We support a call for transformative WASH, in so much as it encapsulates the guiding principle that - in any context - a comprehensive package of WASH interventions is needed that is tailored to address the local exposure landscape and enteric disease burden

Injury Mortality in Texas and the Lower Rio Grande Valley, 1980-1998

Aims: To compare age-adjusted injury mortality rates between Lower Rio Grande Valley (LRGV) Hispanics, Texas Hispanics and Texas Whites. Methods: Using data from the Texas Department of Health, we examined deaths from injuries including: motor vehicle accidents, homicide, and suicide from 1980 through 1998. Results: Injury deaths are the fourth leading cause of death in Texas. Mortality rates for all-cause injuries among LRGV Hispanics were 25% lower than rates among Texas Whites. Traffic accident mortality were quite similar among the study groups. From 1980, the average mortality from traffic accidents per 100,000 persons was 21.9 among Whites and 27.2 among LRGV Hispanics; in 1998 the respective rates were 19.3 and 15.2. Mortality from homicide is higher among Texas Hispanics than among Texas Whites and LRGV Hispanics. Although rates have been declining among all groups, Texas Hispanics still have approximately 3 times the homicide mortality as Texas Whites and LRGV Hispanics. In 1980, LRGV Hispanics had 25% more homicides than did Texas Whites and in 1998, they had 80% more homicide deaths. Suicide death rates are highest among Texas Whites and are similar among Texas and LRGV Hispanics. Hispanics experience half the suicide deaths as Texas Whites. However, suicide deaths have decreased nearly 10% among Texas Whites, nearly 20% among Texas Hispanics, and have remained constant among LRGV Hispanics. Over the study period, the difference in mortality has declined, primarily due to decreases in changes favorable to Texas Whites and unfavorable to LRGV Hispanics

Getting Reluctant Students to Engage With Critical Topics: The Power of Literary Learning Circles

Presenters will discuss their efforts to develop and implement an innovative small group, literary learning circle assignment in a graduate level Social Policy course. This new assignment was based on and adapted from the ETE Faculty Learning Circle model and was specifically designed to improve student engagement with challenging course material in a high resistance topic area. Based on preliminary data from a formal and comprehensive evaluation of students\u27 experience with this pedagogical approach, the learning circle assignment was exceptionally popular with students and extremely effective in increasing student engagement with, and understanding of critical, but previously unpopular course material