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1.
J Org Chem ; 89(11): 7913-7926, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38778786

ABSTRACT

A one-pot procedure for the oxidative amidation of aldehydes via the in situ generation of reactive nitrile imine (NI) intermediates has been developed. Distinct from our progenitor processes, mechanistic and control experiments revealed that the NI undergoes rapid oxidation to an acyl diazene species, which then facilitates N-acylation of an amine. A range of substrates have been explored, including application in the synthesis of pharmaceutically relevant compounds.

2.
Brain Commun ; 6(1): fcae008, 2024.
Article in English | MEDLINE | ID: mdl-38304004

ABSTRACT

The 18 kDa translocator protein is a well-known biomarker of neuroinflammation, but also plays a role in homeostasis. PET with 18 kDa translocator protein radiotracers [11C]PBR28 in humans and [18F]GE180 in mice has demonstrated sex-dependent uptake patterns in the healthy brain, suggesting sex-dependent 18 kDa translocator protein expression, although humans and mice had differing results. This study aimed to assess whether the 18 kDa translocator protein PET radiotracer [18F]LW223 exhibited sexually dimorphic uptake in healthy murine brain and peripheral organs. Male and female C57Bl6/J mice (13.6 ± 5.4 weeks, 26.8 ± 5.4 g, mean ± SD) underwent 2 h PET scanning post-administration of [18F]LW223 (6.7 ± 3.6 MBq). Volume of interest and parametric analyses were performed using standard uptake values (90-120 min). Statistical differences were assessed by unpaired t-test or two-way ANOVA with Sidak's test (alpha = 0.05). The uptake of [18F]LW223 was significantly higher across multiple regions of the male mouse brain, with the most pronounced difference detected in hypothalamus (P < 0.0001). Males also exhibited significantly higher [18F]LW223 uptake in the heart when compared to females (P = 0.0107). Data support previous findings on sexually dimorphic 18 kDa translocator protein radiotracer uptake patterns in mice and highlight the need to conduct sex-controlled comparisons in 18 kDa translocator protein PET imaging studies.

3.
J Cereb Blood Flow Metab ; 44(3): 397-406, 2024 03.
Article in English | MEDLINE | ID: mdl-37795635

ABSTRACT

Neuroinflammation is associated with a number of brain diseases, making it a common feature of cerebral pathology. Among the best-known biomarkers for neuroinflammation in Positron Emission Tomography (PET) research is the 18 kDa translocator protein (TSPO). This study aims to investigate the binding kinetics of a novel TSPO PET radiotracer, [18F]LW223, in mice and specifically assess its volume of non-displaceable binding (VND) in brain as well as investigate the use of simplified analysis approaches for quantification of [18F]LW223 PET data. Adult male mice were injected with [18F]LW223 and varying concentrations of LW223 (0.003-0.55 mg/kg) to estimate VND of [18F]LW223. Dynamic PET imaging with arterial input function studies and radiometabolite studies were conducted. Simplified quantification methods, standard uptake values (SUV) and apparent volume of distribution (VTapp), were investigated. [18F]LW223 had low VND in the brain (<10% of total binding) and low radiometabolism (∼15-20%). The 2-tissue compartment model provided the best fit for [18F]LW223 PET data, although its correlation with SUV90-120min or VTapp allowed for [18F]LW223 brain PET data quantification in healthy animals while using simpler experimental and analytical approaches. [18F]LW223 has the required properties to become a successful TSPO PET radiotracer.


Subject(s)
Neuroinflammatory Diseases , Receptors, GABA , Male , Mice , Animals , Receptors, GABA/metabolism , Brain/diagnostic imaging , Brain/metabolism , Positron-Emission Tomography/methods , Carrier Proteins/metabolism
4.
ACS Med Chem Lett ; 14(12): 1800-1806, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38116409

ABSTRACT

The androgen receptor (AR) is central to prostate cancer pathogenesis and has been extensively validated as a drug target. However, small-molecule anti-androgen therapies remain limited due to resistance and will eventually fail to suppress tumor growth, resulting in progression to castration-resistant prostate cancer (CRPC). The intrinsically disordered N-terminal domain (NTD) is crucial for AR transactivation and has been investigated as a suitable target in the presence of ligand binding domain mutations. A screening campaign identified biaryl isoxazole compound 7 as a weak inhibitor of the AR NTD. A library of biaryl analogues were synthesized, and their biological activities were assessed in a VCaP cell-based luciferase reporter gene assay. A structure-activity relationship (SAR) study revealed that indazole analogue 16 exhibited increased potency and favorable physicochemical properties with a benchmarked pharmacokinetic profile, providing a suitable starting point for further optimization of 16 as a CRPC therapeutic in the presence of AR mutations.

5.
Alzheimers Res Ther ; 15(1): 168, 2023 10 06.
Article in English | MEDLINE | ID: mdl-37803386

ABSTRACT

Tauopathies are a group of neurodegenerative disorders characterized by the aggregation of the microtubule-associated protein tau. Aggregates of misfolded tau protein are believed to be implicated in neuronal death, which leads to a range of symptoms including cognitive decline, behavioral change, dementia, and motor deficits. Currently, there are no effective treatments for tauopathies. There are four clinical candidates in phase III trials and 16 in phase II trials. While no effective treatments are currently approved, there is increasing evidence to suggest that various therapeutic approaches may slow the progression of tauopathies or improve symptoms. This review outlines the landscape of therapeutic drugs (indexed through February 28, 2023) that target tau pathology and describes drug candidates in clinical development as well as those in the discovery and preclinical phases. The review also contains information on notable therapeutic programs that are inactive or that have been discontinued from development.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Tauopathies , Humans , Brain/metabolism , Tauopathies/drug therapy , Tauopathies/metabolism , tau Proteins/metabolism , Cognitive Dysfunction/metabolism , Alzheimer Disease/pathology
6.
Med Res Rev ; 43(5): 1701-1747, 2023 09.
Article in English | MEDLINE | ID: mdl-37062876

ABSTRACT

The androgen receptor (AR) has been shown to be a key determinant in the pathogenesis of castration-resistant prostate cancer (CRPC). The current standard of care therapies targets the ligand-binding domain of the receptor and can afford improvements to life expectancy often only in the order of months before resistance occurs. Emerging preclinical and clinical compounds that inhibit receptor activity via differentiated mechanisms of action which are orthogonal to current antiandrogens show promise for overcoming treatment resistance. In this review, we present an authoritative summary of molecules that noncompetitively target the AR. Emerging small molecule strategies for targeting alternative domains of the AR represent a promising area of research that shows significant potential for future therapies. The overall quality of lead candidates in the area of noncompetitive AR inhibition is discussed, and it identifies the key chemotypes and associated properties which are likely to be, or are currently, positioned to be first in human applications.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Receptors, Androgen , Male , Humans , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Androgen Antagonists/therapeutic use , Cell Line, Tumor
7.
J Environ Manage ; 327: 116817, 2023 Feb 01.
Article in English | MEDLINE | ID: mdl-36459786

ABSTRACT

River barriers reduce river connectivity and lead to fragmentation of fish habitats, which can result in decline or even extinction of aquatic biota, including fish populations. In the Mekong basin, previous studies have mainly focused on the impacts of large dams but ignored the impacts of small-scale barriers, or drew conclusions from incomplete barrier databases, potentially leading to research biases. To test the completeness of existing databases and to evaluate the catchment-scale fragmentation level, a detailed investigation of river barriers for the whole Upper Mekong (Lancang catchment) was performed, by conducting visual interpretation of high-resolution remotely sensed images. Then, a complete catchment-scale barrier database was created for the first time. By comparing our barrier database with existing databases, this study indicates that 93.7% of river barriers were absent from the existing database, including 75% of dams and 99.5% of small barriers. Barrier density and dendritic connectivity index (DCID and DCIP) were used to measure channel fragmentation within the catchment. Overall, 50.5% of sub-catchments contained river barriers. The Middle region is the most fragmented area within the Lancang catchment, with a median [quartiles] barrier density of 5.34 [0.70-9.67] per 100 km, DCIP value of 49.50 [21.50-90.00] and DCID value of 38.50 [9.00-92.25]. Furthermore, since 2010, distribution ranges of two representative fish species Schizothorax lissolabiatus (a rheophilic cyprinid) and Bagarius yarrelli (a large catfish) have reduced by 19.2% and 32.8% respectively, probably due in part to the construction of river barriers. Our findings indicate that small-scale barriers, in particular weirs and also small dams are the main reason for habitat fragmentation in the Lancang and must be considered alongside large dams in water management and biodiversity conservation within the Mekong.


Subject(s)
Fishes , Rivers , Animals , Biodiversity , Ecosystem , Biota
8.
Org Lett ; 24(51): 9491-9496, 2022 12 30.
Article in English | MEDLINE | ID: mdl-36524745

ABSTRACT

We report the use of N-2,4-dinitrophenyltetrazoles as latent active esters (LAEs) in the synthesis of amide bonds. Activating the tetrazole generates an HOBt-type active ester without the requirement for exogenous coupling agents. The methodology was widely applicable to a range of substrates, with up to quantitative yields obtained. The versatility and functional group tolerance were exemplified with the one-step synthesis of various pharmaceutical agents and the N-acylation of resin-bound peptides.


Subject(s)
Amides , Esters , Peptides , Acylation , Tetrazoles/chemistry
9.
Fac Rev ; 11: 9, 2022.
Article in English | MEDLINE | ID: mdl-35509672

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is an intractable cancer and a leading cause of cancer deaths worldwide. Over 90% of patients die within 1 year of diagnosis. Deaths from PDAC are increasing and it remains a cancer of substantial unmet need. A number of factors contribute to its poor prognosis: namely, late presentation, early metastases and limited systemic therapy options because of chemoresistance. A variety of research approaches underway are aimed at improving patient survival. Here, we review high-risk groups and efforts for early detection. We examine recent developments in the understanding of complex molecular and metabolic alterations which accompany PDAC. We explore artificial intelligence and biological targets for therapy and examine the role of tumour stroma and the immune microenvironment. We also review recent developments with respect to the PDAC microbiome. It is hoped that current research efforts will translate into earlier diagnosis, improvements in treatment and better outcomes for patients.

10.
Front Surg ; 9: 860721, 2022.
Article in English | MEDLINE | ID: mdl-35465416

ABSTRACT

Objectives: Mortality and morbidity following hepatic resection is significantly affected by major intra-operative blood loss. This systematic review and meta-analysis evaluates whether selective hepatic vascular exclusion (SHVE) compared to a Pringle maneuver in hepatic resection reduces rates of morbidity and mortality. Methods: A systematic review and meta-analysis were conducted according to the PRISMA guidelines by screening EMBASE, MEDLINE/PubMed, CENTRAL and SCOPUS for comparative studies meeting the inclusion criteria. Pooled odds ratios or mean differences were calculated for outcomes using either fixed- or random-effects models. Results: Six studies were identified: three randomised controlled trials and three observational studies reporting a total of 2,238 patients. Data synthesis showed significantly decreased rates of mortality, overall complications, blood loss, transfusion requirements, air embolism, liver failure and multi-organ failure in the SHVE group. Rates of hepatic vein rupture, post-operative hemorrhage, operative and warm ischemia time, length of stay in hospital and intensive care unit were not statistically significant between the two groups. Conclusion: Performing SHVE in major hepatectomy may result in reduced rates of morbidity and mortality when compared to a Pringle maneuver. The results of this meta-analysis are based on studies where tumors were adjacent to major vessels. Further RCTs are required to validate these results. Clinical Trial Registration: PROSPERO (CRD42020212372) https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=212372.

11.
Sci Rep ; 12(1): 1114, 2022 01 21.
Article in English | MEDLINE | ID: mdl-35064119

ABSTRACT

There is increasing evidence that personality traits may drive dispersal patterns of animals, including invasive species. We investigated, using the widespread signal crayfish Pacifastacus leniusculus as a model invasive species, whether effects of personality traits on dispersal were independent of, or affected by, other factors including population density, habitat, crayfish size, sex and limb loss, along an invasion gradient. Behavioural traits (boldness, activity, exploration, willingness to climb) of 310 individually marked signal crayfish were measured at fully-established, newly-established and invasion front sites of two upland streams. After a period at liberty, recaptured crayfish were reassessed for behavioural traits (newly-established, invasion front). Dispersal distance and direction of crayfish movement, local population density, fine-scale habitat characteristics and crayfish size, sex and limb loss were also measured. Individual crayfish exhibited consistency in behavioural traits over time which formed a behavioural syndrome. Dispersal was both positively and negatively affected by personality traits, positively by local population density and negatively by refuge availability. No effect of size, sex and limb loss was recorded. Personality played a role in promoting dispersal but population density and local habitat complexity were also important determinants. Predicting biological invasion in animals is likely to require better integration of these processes.


Subject(s)
Animal Distribution/physiology , Astacoidea/physiology , Behavior, Animal/physiology , Introduced Species , Animals , Ecosystem , England , Population Density , Rivers
12.
Org Lett ; 24(1): 334-338, 2022 01 14.
Article in English | MEDLINE | ID: mdl-34964648

ABSTRACT

We report how the rearrangement of highly reactive nitrile imines derived from N-2-nitrophenyl hydrazonyl bromides can be harnessed for the facile construction of amide bonds. This amidation reaction was found to be widely applicable to the synthesis of primary, secondary, and tertiary amides and was used as the key step in the synthesis of the lipid-lowering agent bezafibrate. The orthogonality and functional group tolerance of this approach was exemplified by the N-acylation of unprotected amino acids.

13.
Sci Total Environ ; 802: 149720, 2022 Jan 01.
Article in English | MEDLINE | ID: mdl-34464804

ABSTRACT

Barrier removal and fish pass construction are increasingly used as tools to restore river connectivity and improve habitat quality, but the effectiveness of subcatchment-scale connectivity restoration on recovery of fish communities is poorly understood. We used a before-after-downstream-upstream methodology to determine the effects of subcatchment-scale connectivity restoration on fishes in a fragmented tributary of the River Wear, Northeast England, between 2013 and 2019. Following restoration (three barriers removed, five barriers fitted with fish passes, two barriers unaltered), riffle habitat increased, fine sediment decreased, and most fish species benefitted. Total fish abundance, comprising seven native species, increased 3 years after the restoration and remained elevated to the end of the study. Mean brown trout (Salmo trutta) density increased from 20.9 ±â€¯6.3 to 33.8 ±â€¯16.8 per 100m2 from 2013 to 2019, with Young-of-Year trout increasing from 10.6 ±â€¯4.6 to 19.8 ±â€¯11.8 per 100m2. Connectivity restoration reduced the mean age of trout, suggesting a change to an increased migratory component of the population. Density of bullhead (Cottus perifretum), a species with poor dispersal ability, increased from 4.6 ±â€¯2.7 to 32.6 ±â€¯17.9 per 100m2 over 2013 to 2019. Stone loach (Barbatula barbatula), also a less mobile species but tolerant to fine sediment, decreased in abundance where barriers were removed. Atlantic salmon (Salmo salar) were absent over the study timescale, despite being common in the Wear, and despite suitable habitat and water quality in the restored subcatchment, suggesting a hysteresis effect. Our findings indicate that, where good water quality exists, restoring river connectivity and hydromorphology at a subcatchment scale is beneficial for most native resident and migratory fishes. However, the ecological benefits of connectivity restoration, especially in rivers with many barriers, may take several years to develop. We encourage well-controlled long-term studies reporting the outcomes of large-scale connectivity restoration.


Subject(s)
Cypriniformes , Perciformes , Animals , Ecosystem , Fishes , Rivers , Trout
14.
Ecol Evol ; 11(17): 11974-11990, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34522354

ABSTRACT

Variations in behavioral traits are widely recognized to drive animal behaviors exhibited within a population. However, information on how behavior traits influence behavior in anthropogenically modified habitats is lacking. Many habitats have become highly fragmented as a result of human processes. To mitigate this and improve habitat connectivity, wildlife passes are increasingly employed, with the aim of enabling animals to move freely between habitats. However, wildlife passes (e.g., fishways) are not always effective in achieving passage and it remains uncertain what factors play a role in an individual's likelihood of passing successfully. This study measured three behavioral traits (boldness, exploration, and activity) in juvenile brown trout (Salmo trutta; n = 78) under field conditions within a river and tested whether these behavior traits influenced both the passage success and the behaviors exhibited during upstream fishway passage attempts. Although behavioral traits were found and collapsed into two behavioral trait dimensions, behavioral traits had low repeatability and so did not contribute to a personality spectrum. Boldness was found to negatively influence the number of passage attempts carried out by an individual and to positively influence passage success, with bolder individuals carrying out fewer attempts and having an increased probability of passage success. No behavioral traits were found to be related to other passage metrics (passage success, Time until First Attempt, and Passage Duration) during the first passage. But all three behavioral traits were significantly negatively related to the changes in passage behaviors at consecutive, successful passage attempts, with bolder, more exploratory and more active individuals passing through a fishway quicker on the second passage than on the first. This study suggests that bolder and more active individuals may perform better during fishway passage attempts, particularly within rivers where multiple barriers to movement exist.

15.
World J Surg ; 45(11): 3404-3413, 2021 11.
Article in English | MEDLINE | ID: mdl-34322717

ABSTRACT

BACKGROUNDS: Colorectal liver metastases were historically considered a contraindication to liver transplantation, but dismal outcomes for those with metastatic colorectal cancer and advancements in liver transplantation (LT) have led to a renewed interest in the topic. We aim to compare the current evidence for liver transplantation for non-resectable colorectal liver metastases (NRCLM) with the current standard treatment of palliative chemotherapy. METHODS: A systematic review and meta-analysis of proportions was conducted following screening of MEDLINE, EMBASE, SCOPUS and CENTRAL for studies reporting liver transplantation for colorectal liver metastases. Post-operative outcomes measured included one-, three- and five-year survival, overall survival, disease-free survival and complication rate. RESULTS: Three non-randomised studies met the inclusion criteria, reporting a total of 48 patients receiving LT for NRCLM. Survival at one-, three- and five-years was 83.3-100%, 58.3-80% and 50-80%, respectively, with no significant difference detected (p = 0.22, p = 0.48, p = 0.26). Disease-free survival was 35-56% with the most common site of recurrence being lung. Thirteen out of fourteen deaths were due to disease recurrence. CONCLUSION: Although current evidence suggests a survival benefit conferred by LT in NRCLM compared to palliative chemotherapy, the ethical implications of organ availability and allocation demand rigorous justification. Concomitant improvements in the management of patients following liver resection and of palliative chemotherapy regimens is paramount.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Liver Transplantation , Colorectal Neoplasms/surgery , Hepatectomy , Humans , Liver Neoplasms/surgery , Neoplasm Recurrence, Local
16.
Int J Surg ; 88: 105923, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33774175

ABSTRACT

BACKGROUND: Post-operative pancreatic fistula (POPF) and delayed gastric emptying (DGE) both remain problematic complications following pancreaticoduodenectomy. This systematic review and meta-analysis evaluates whether Roux-en-Y compared to a single loop reconstruction in pancreaticoduodenectomy significantly reduces rates of these complications. METHODS: A systematic review and meta-analysis was conducted according to the PRISMA guidelines by screening EMBASE, MEDLINE/PubMed, CENTRAL and bibliographic reference lists for comparative studies meeting the predetermined inclusion criteria. Post-operative outcome measures included: POPF, DGE, bile leak, operating time, blood loss, need for transfusion, wound infection, intra-abdominal collection, post-pancreatectomy haemorrhage, overall morbidity, re-operation, overall mortality, hospital length of stay. Pooled odds ratios or mean differences with 95% confidence intervals were calculated using either fixed- or random-effects models. RESULTS: Fourteen studies were identified including four randomised controlled trials (RCTs) and 10 observational studies reporting a total of 2,031 patients. Data synthesis showed no statistically significant difference between the two groups in any of the outcome measures except operating time, which was longer in those undergoing Roux-en-Y reconstruction. DISCUSSION: Roux-en-Y is not superior to single loop reconstruction in pancreaticoduodenectomy but may prolong operating time. Future high-quality randomised studies with appropriate study design and sample size power calculation may be required to further validate this conclusion.


Subject(s)
Anastomosis, Roux-en-Y/methods , Pancreaticoduodenectomy/methods , Plastic Surgery Procedures/methods , Humans , Operative Time , Pancreaticoduodenectomy/adverse effects , Postoperative Complications/prevention & control , Plastic Surgery Procedures/adverse effects
17.
Surgery ; 170(3): 650-656, 2021 09.
Article in English | MEDLINE | ID: mdl-33612291

ABSTRACT

BACKGROUND: Social media has an increasing role within professional surgical practice, including the publishing and engagement of academic literature. This study aims to analyze the relationship between social media use and traditional and alternative metrics among academic surgical journals. METHOD: Journals were identified through the InCites Journal Citation Reports 2019, and their impact factor, h-index, and CiteScore were noted. Social media platforms were examined, and Twitter activity interrogated between 1 January to 31 December 2019. Healthcare Social Graph score and an aggregated Altmetric Attention Score were also calculated for each journal. Statistical analysis was carried out to look at the correlation between traditional metrics, Twitter activity, and altmetrics. RESULTS: Journals with a higher impact factor were more likely to use a greater number of social media platforms (R2 = 0.648; P < .0001). Journals with dedicated Twitter profiles had a higher impact factor than journals without (median, 2.96 vs 1.88; Mann-Whitney U = 390; P < .001); however, over a 1-year period (2018-2019) having a Twitter presence did not alter impact factor (Mann-Whitney U = 744.5; P = .885). Increased Twitter activity was positively correlated with impact factor. Longitudinal analysis over 6 years suggested cumulative tweets correlated with an increased impact factor (R2 = 0.324, P = .004). Novel alternative measures including Healthcare Social Graph score (R2 = 0.472, P = .005) and Altmetric Attention Score (R2 = 0.779, P = .001) positively correlated with impact factor. CONCLUSION: Higher impact factor is associated with social media presence and activity, particularly on Twitter, with long-term activity being of particular importance. Modern alternative metrics correlate with impact factor. This relationship is complex, and future studies should look to understand this further.


Subject(s)
Benchmarking , General Surgery/organization & administration , Periodicals as Topic/trends , Professional Practice/standards , Publishing/organization & administration , Research Design/standards , Social Media/trends , Bibliometrics , Humans , Retrospective Studies
18.
BMJ Qual Saf ; 30(1): 27-37, 2021 01.
Article in English | MEDLINE | ID: mdl-32217699

ABSTRACT

BACKGROUND: Improving the quality and efficiency of healthcare is an international priority. A range of complex ward based quality initiatives have been developed over recent years, perhaps the most influential programme has been Productive Ward: Releasing Time to Care. The programme aims to improve work processes and team efficiency with the aim of 'releasing time', which would be used to increase time with patients ultimately improving patient care, although this does not form a specific part of the programme. This study aimed to address this and evaluate the impact using recent methodological advances in complex intervention evaluation design. METHOD: The objective of this study was to assess the impact of an augmented version of The Productive Ward: Releasing Time to Care on staff and patient outcomes. The design was a naturalistic stepped-wedge trial. The setting included fifteen wards in two acute hospitals in a Scottish health board region. The intervention was the Productive Ward: Releasing Time to Care augmented with practice development transformational change methods that focused on staff caring behaviours, teamwork and patient feedback. The primary outcomes included nurses' shared philosophy of care, nurse emotional exhaustion, and patient experience of nurse communication. Secondary outcomes covered additional key dimensions of staff and patient experience and outcomes and frequency of emergency admissions for same diagnosis within 6 months of discharge. RESULTS: We recruited 691 patients, 177 nurses and 14 senior charge nurses. We found statistically significant improvements in two of the study's three primary outcomes: patients' experiences of nurse communication (Effect size=0.15, 95% CI; 0.05 to 0.24), and nurses' shared philosophy of care (Effect size =0.42, 95% CI; 0.14 to 0.70). There were also significant improvements in secondary outcomes: patients' overall rating of ward quality; nurses' positive affect; and items relating to nursing team climate. We found no change in frequency of emergency admissions within six months of discharge. CONCLUSIONS: We found evidence that the augmented version of The Productive Ward: Releasing Time to Care Intervention was successful in improving a number of dimensions of nurse experience and ward culture, in addition to improved patient experience and evaluations of the quality of care received. Despite these positive summary findings across all wards, intervention implementation appeared to vary between wards. By addressing the contextual factors, which may influence these variations, and tailoring some elements of the intervention, it is likely that greater improvements could be achieved. TRIAL REGISTRATION NUMBER: UKCRN 14195.


Subject(s)
Communication , Hospitals , Delivery of Health Care , Humans , Patient Care
19.
Nature ; 588(7838): 436-441, 2020 12.
Article in English | MEDLINE | ID: mdl-33328667

ABSTRACT

Rivers support some of Earth's richest biodiversity1 and provide essential ecosystem services to society2, but they are often fragmented by barriers to free flow3. In Europe, attempts to quantify river connectivity have been hampered by the absence of a harmonized barrier database. Here we show that there are at least 1.2 million instream barriers in 36 European countries (with a mean density of 0.74 barriers per kilometre), 68 per cent of which are structures less than two metres in height that are often overlooked. Standardized walkover surveys along 2,715 kilometres of stream length for 147 rivers indicate that existing records underestimate barrier numbers by about 61 per cent. The highest barrier densities occur in the heavily modified rivers of central Europe and the lowest barrier densities occur in the most remote, sparsely populated alpine areas. Across Europe, the main predictors of barrier density are agricultural pressure, density of river-road crossings, extent of surface water and elevation. Relatively unfragmented rivers are still found in the Balkans, the Baltic states and parts of Scandinavia and southern Europe, but these require urgent protection from proposed dam developments. Our findings could inform the implementation of the EU Biodiversity Strategy, which aims to reconnect 25,000 kilometres of Europe's rivers by 2030, but achieving this will require a paradigm shift in river restoration that recognizes the widespread impacts caused by small barriers.


Subject(s)
Ecosystem , Rivers , Agriculture/statistics & numerical data , Altitude , Biodiversity , Datasets as Topic , Environmental Restoration and Remediation/methods , Environmental Restoration and Remediation/trends , Europe , Human Activities , Humans , Logistic Models , Machine Learning , Population Density , Power Plants/supply & distribution
20.
Biomed Res Int ; 2020: 6987198, 2020.
Article in English | MEDLINE | ID: mdl-33083478

ABSTRACT

BACKGROUND: The development and transformation of nursing within professional tertiary education have exerted a great pressure and challenge upon nursing students. Stress experienced by nursing students is a common precursor of psychological distress and attrition. However, no scale is specifically used to evaluate the sources of stress experienced by nursing students in Mainland China. Aims and Objective. This study is aimed at testing and comparing the reliability and validity including sensitivity and specificity of two nursing students' stress instruments, the Chinese version of Student Nurse Stress Index Scale (SNSI-CHI), and the Stressors in Student Nursing Scale (SINS-CN) in Chinese nursing students, and describing the stress status of nursing students in China. METHODS: A cross-sectional survey was conducted in two nursing schools in Henan Province from August 2017 to January 2018. Data were collected by using a questionnaire comprising the Chinese version of SNSI (SNSI-CHI), the Chinese version of SINS (SINS-CN), and the Chinese Perceived Stress Scale (CPSS). Homogeneity and stability, content, construct and concurrent validity, and sensitivity and specificity were assessed. RESULTS: The Cronbach's alpha (α) of SNSI-CHI was 0.90, and the item-to-total correlations ranged from 0.35 to 0.66. The Cronbach's α of SINS-CN was 0.93, and the item-to-total correlations ranged from 0.19 to 0.61. The findings of exploratory factor analysis (EFA) confirmed a good construct validity of SNSI-CHI and SINS-CN. The Pearson's rank correlation coefficients, between total scores of SNSI-CHI and CPSS and SINS-CN and CPSS, were assessed to 0.38 (P < 0.01) and 0.39 (P < 0.01), respectively. Regarding the CPSS, as the criterion, the cut-points of SNSI-CHI and SINS-CN for the area under the receiver operator characteristic (ROC) curve were 0.77and 0.66, respectively. CONCLUSION: Both scales are valid and reliable for evaluating the source of stress of student nurses in China. Each has its own characteristics, but the SNSI-CHI demonstrated marginal advantage over the SINS-CN. The SNSI-CHI is short, is easily understood, and with clear dimension for the nursing students, and the SNSI-CHI is more acceptable for the users in China.


Subject(s)
Psychometrics , Stress, Psychological/epidemiology , Students, Nursing , Adolescent , Adult , China/epidemiology , Cross-Sectional Studies , Factor Analysis, Statistical , Female , Humans , Male , Psychometrics/methods , Psychometrics/standards , Students, Nursing/psychology , Students, Nursing/statistics & numerical data , Surveys and Questionnaires , Young Adult
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