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Cytochrome bd–type quinol oxidases catalyze the reduction of molecular oxygen to water in the respiratory chain of many human-pathogenic bacteria. They are structurally unrelated to mitochondrial cytochrome c oxidases and are therefore a prime target for the development of antimicrobial drugs. We determined the structure of the Escherichia coli cytochrome bd-I oxidase by single-particle cryo–electron microscopy to a resolution of 2.7 angstroms. Our structure contains a previously unknown accessory subunit CydH, the L-subfamily–specific Q-loop domain, a structural ubiquinone-8 cofactor, an active-site density interpreted as dioxygen, distinct water-filled proton channels, and an oxygen-conducting pathway. Comparison with another cytochrome bd oxidase reveals structural divergence in the family, including rearrangement of high-spin hemes and conformational adaption of a transmembrane helix to generate a distinct oxygen-binding site.

The average annual base flow/recharge was determined for streamflow-gaging stations throughout Wisconsin by base-flow separation. A map of the State was prepared that shows the average annual base flow for the period 1970-99 for watersheds at 118 gaging stations. Trend analysis was performed on 22 of the 118 streamflow-gaging stations that had long-term records, unregulated flow, and provided aerial coverage of the State. The analysis found that a statistically significant increasing trend was occurring for watersheds where the primary land use was agriculture. Most gaging stations where the land cover was forest had no significant trend. A method to estimate the average annual base flow at ungaged sites was developed by multiple-regression analysis using basin characteristics. The equation with the lowest standard error of estimate, 9.5%, has drainage area, soil infiltration and base flow factor as independent variables. To determine the average annual base flow for smaller watersheds, estimates were made at low-flow partial-record stations in 3 of the 12 major river basins in Wisconsin. Regression equations were developed for each of the three major river basins using basin characteristics. Drainage area, soil infiltration, basin storage and base-flow factor were the independent variables in the regression equations with the lowest standard error of estimate. The standard error of estimate ranged from 17% to 52% for the three river basins.

The consumption of shallow groundwater with elevated concentrations of arsenic is causing widespread disease in many parts of South and Southeast Asia. In the Bengal Basin, a growing reliance on groundwater sourced below 150-m depth—where arsenic concentrations tend to be lower—has reduced exposure. Groundwater flow simulations have suggested that these deep waters are at risk of contamination due to replenishment with high-arsenic groundwater from above, even when deep water pumping is restricted to domestic use. However, these simulations have neglected the influence of sediment adsorption on arsenic migration. Here, we inject arsenic-bearing groundwater into a deep aquifer zone in Bangladesh, and monitor the reduction in arsenic levels over time following stepwise withdrawal of the water. Arsenic concentrations in the injected water declined by 70% after 24 h in the deep aquifer zone, owing to adsorption on sediments; concentrations of a co-injected inert tracer remain unchanged. We incorporate the experimentally determined adsorption properties of sands in the deep aquifer zone into a groundwater flow and transport model covering the Bengal Basin. Simulations using present and future scenarios of water-use suggest that arsenic adsorption significantly retards transport, thereby extending the area over which deep groundwater can be used with low risk of arsenic contamination. Risks are considerably lower when deep water is pumped for domestic use alone. Some areas remain vulnerable to arsenic intrusion, however, and we suggest that these be prioritized for monitoring. Elevated concentrations of arsenic are common in shallow groundwater in many parts of South and Southeast Asia. Field experiments and model simulations suggest that adsorption of arsenic to sediments could help to limit contamination of deep groundwater.

As a non-invasive monitoring method camera traps are noted as being an effective, accurate and rapid means of compiling species richness estimates of medium to large terrestrial mammals. However, crucial elements of camera trap survey design are rarely empirically addressed, which has raised the need for both a standardised and optimised camera trapping protocol. Our study confirms that an appropriate camera placement buffer and targeting areas of animal activity, contributes to more complete species richness estimates as well as significantly reducing the rate of false trigger events. However, attaining the required survey effort in terms of camera days was the most important factor in providing accurate species richness estimates. Our results suggest that reliable estimates of species richness can be achieved in open scrubland when cameras are spaced 1 × 1 km apart and left in the targeted area until a survey effort of a 1000 camera days is realised.

I am a relatively new fan to the sport of horse racing, but I am nonetheless enthusiastic. I look forward to the excitement of a day at the races with all its trappings; the regulars who always have an opinion on the next race, the smells and sounds, the joy on the faces of the winners as well as the disappointment of the not-so-lucky. I myself have wagered a bet from time to time. But win or lose, it's the sport itself and the elegance of a thoroughbred in motion that will always bring me back.

Urbanisation is associated with the loss and fragmentation of natural land, the disruption of ecosystem functioning and services, and the loss of biodiversity. Cape Town is situated in a global biodiversity hotspot, with high rates of endemism, but both agricultural and housing demands are increasing pressure on remaining patches of natural land and consequently the biodiversity they support. The aims of this study were to use a standardised camera trap survey to determine which native medium and large mammal species still survive in 12 City of Cape Town (CCT) municipal reserves (range 32–8400 ha), and to understand how reserve size, area-perimeter ratio, connectivity, habitat heterogeneity and presence of permanent freshwater aquatic habitat might influence medium and large mammal (>0.5 kg) community composition. Cameras were placed at 151 locations across all reserves using a stratified placement protocol that resulted in 13,360 independent trigger events by targeted taxa. Nineteen native species (11 carnivores, 7 herbivores, 1 omnivore) were recorded, which is 49% of the 39 species believed to have been present historically. Species richness varied from 1 to 12 species (mean ± SD = 7 ± 3.6) across reserves, and linear models showed that higher species richness and the presence of large carnivores was best explained by improved connectivity to large amounts of natural habitat. It is recommended that maintaining biodiversity in urban reserves will be best achieved by preserving and establishing corridors of suitable habitat that allow for the movement of animals to and from other patches.

Background Many patients with Alzheimer’s disease (AD) are physically frail or have substantial functional impairments. There is growing evidence that such patients are at higher risk for medication-induced adverse events. Furthermore, frailty seems to be more predictive of poor clinical outcomes than chronological age alone. To our knowledge, no systematic review of clinical trials examining drug therapy of AD or behavioural and psychological symptoms of dementia (BPSD) has specifically focused on the topic of physical frailty. Our objective was to evaluate the efficacy and safety of pharmacotherapy in AD patients with frailty or significant functional impairments. Methods We performed a systematic literature search in MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) of drug therapy of AD and BPSD in patients with significant functional impairments according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Cochrane research criteria. Significant functionally impaired patient populations were identified using the recommendations of the Medication and Quality of Life in frail older persons (MedQoL) Research Group. Screening, selection of studies, data extraction and risk of bias assessment were performed independently by two reviewers. Outcomes including functional status, cognitive function, changes in BPSD symptoms, clinical global impression and quality of life were analysed. For assessing harm, we assessed adverse events, drop-outs as a proxy for treatment tolerability and death. Results were analysed according to Cochrane standards and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Of 45,045 search results, 38,447 abstracts and 187 full texts were screened, and finally, 10 RCTs were included in the systematic review. Selected articles evaluated pharmacotherapy with acetylcholinesterase-inhibitors (AChEI), anticonvulsants, antidepressants and antipsychotics. Studies of AChEIs suggested that patients with significant functional impairments had slight but significant improvements in cognition and that AChEIs were generally well tolerated. Studies of antidepressants did not show significant improvements in depressive symptoms. Antipsychotics and anticonvulsants showed small effects on some BPSD items but also higher rates of adverse events. However, due to the very small number of identified trials, the quality of evidence for all outcomes was low to very low. Overall, the small number of eligible studies demonstrates that significantly functional impaired older patients have not been adequately taken into consideration in most clinical trials investigating drug therapy of AD and BPSD. Conclusion Due to lack of evidence, it is not possible to give specific recommendations for drug therapy of AD and BSPD in frail older patients or older patients with significant functional impairments. Therefore, clinical trials focussing on frail older adults are urgently required. A standardized approach to physical frailty in future clinical studies is highly desirable.

Background Within the ageing population of Western societies, an increasing number of older people have multiple chronic conditions. Because multiple health problems require the involvement of several health professionals, multimorbid older people often face a fragmented health care system. To address these challenges, in a two-group parallel randomized controlled trial, a newly developed care management approach (LoChro-Care) was compared with usual care. Methods LoChro-Care consists of individualized care provided by chronic care managers with 7 to 16 contacts over 12 months. Patients aged 65 + with chronic conditions were recruited from inpatient and outpatient departments. Healthcare utilization costs are calculated by using an adapted version of the generic, self-reporting FIMA©-questionnaire with the application of standardized unit costs. Questionnaires were given at 3 time points (T 0 baseline, T 1 after 12 months, T 2 after 18 months). The primary outcome was overall 3-month costs of healthcare utilization at T 1 and T 2 . The data were analyzed using generalized linear models with log-link and gamma distribution and adjustment for age, sex, level of care as well as the 3-month costs of care at T 0 . Results Three hundred thirty patients were analyzed. The results showed no significant difference in the costs of healthcare utilization between participants who received LoChro-Care and those who received usual care, regardless of whether the costs were evaluated 12 (adjusted mean difference € 130.99, 95%CI €-1477.73 to €1739.71, p = 0.873) or 18 (adjusted mean difference €192.99, 95%CI €-1894.66 to €2280.65, p = 0.856) months after the start of the intervention. Conclusion This study revealed no differences in costs between older people receiving LoChro-Care or usual care. Before implementing the intervention, further studies with larger sample sizes are needed to provide robust evidence on the cost effects of LoChro-Care. Trial registration German Clinical Trials Register (DRKS): DRKS00013904, https://drks.de/search/de/trial/DRKS00013904 ; date of first registration 02/02/2018.