Background A third of older people take five or more regular medications (polypharmacy). Conducting medication reviews in primary care is key to identify and reduce/ stop inappropriate medications (deprescribing). Recent recommendations for effective deprescribing include shared-decision making and a multidisciplinary approach. Our aim was to understand when, why, and how interventions for medication review and deprescribing in primary care involving multidisciplinary teams (MDTs) work (or do not work) for older people. Methods A realist synthesis following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards guidelines was completed. A scoping literature review informed the generation of an initial programme theory. Systematic searches of different databases were conducted, and documents screened for eligibility, with data extracted based on a Context, Mechanisms, Outcome (CMO) configuration to develop further our programme theory. Documents were appraised based on assessments of relevance and rigour. A Stakeholder consultation with 26 primary care health care professionals (HCPs), 10 patients and three informal carers was conducted to test and refine the programme theory. Data synthesis was underpinned by Normalisation Process Theory to identify key mechanisms to enhance the implementation of MDT medication review and deprescribing in primary care. Findings A total of 2821 abstracts and 175 full-text documents were assessed for eligibility, with 28 included. Analysis of documents alongside stakeholder consultation outlined 33 CMO configurations categorised under four themes: 1) HCPs roles, responsibilities and relationships; 2) HCPs training and education; 3) the format and process of the medication review 4) involvement and education of patients and informal carers. A number of key mechanisms were identified including clearly defined roles and good communication between MDT members, integration of pharmacists in the team, simulation-based training or team building training, targeting high-risk patients, using deprescribing tools and drawing on expertise of other HCPs (e.g., nurses and frailty practitioners), involving patents and carers in the process, starting with ‘quick wins’, offering deprescribing as ‘drug holidays’, and ensuring appropriate and tailored follow-up plans that allow continuity of care and management. Conclusion We identified key mechanisms that could inform the design of future interventions and services that successfully embed deprescribing in primary care.
The APOE4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). The contribution of microglial APOE4 to AD pathogenesis is unknown, although APOE has the most enriched gene expression in neurodegenerative microglia (MGnD). Here, we show in mice and humans a negative role of microglial APOE4 in the induction of the MGnD response to neurodegeneration. Deletion of microglial APOE4 restores the MGnD phenotype associated with neuroprotection in P301S tau transgenic mice and decreases pathology in APP/PS1 mice. MGnD–astrocyte cross-talk associated with β-amyloid (Aβ) plaque encapsulation and clearance are mediated via LGALS3 signaling following microglial APOE4 deletion. In the brains of AD donors carrying the APOE4 allele, we found a sex-dependent reciprocal induction of AD risk factors associated with suppression of MGnD genes in females, including LGALS3, compared to individuals homozygous for the APOE3 allele. Mechanistically, APOE4-mediated induction of ITGB8–transforming growth factor-β (TGFβ) signaling impairs the MGnD response via upregulation of microglial homeostatic checkpoints, including Inpp5d, in mice. Deletion of Inpp5d in microglia restores MGnD–astrocyte cross-talk and facilitates plaque clearance in APP/PS1 mice. We identify the microglial APOE4–ITGB8–TGFβ pathway as a negative regulator of microglial response to AD pathology, and restoring the MGnD phenotype via blocking ITGB8–TGFβ signaling provides a promising therapeutic intervention for AD.
Agglutinated foraminiferal assemblages of the Turonian–Coniacian from the GSSP (Global Boundary Stratotype Section and Point) of Salzgitter–Salder (Subhercynian Cretaceous Basin, Germany) and other sections, including Bielefeld–Ostwestfalendamm (Münsterland Cretaceous Basin, Germany) and the Dover–Langdon Stairs (Anglo-Paris Basin, England), from the temperate European shelf realm were studied in order to collect additional stratigraphic and paleoenvironmental information. Stable carbon isotopes were measured for the Bielefeld–Ostwestfalendamm section to establish a reliable stratigraphic correlation with other sections. Highly diverse agglutinated foraminiferal assemblages were obtained from sections in the German basins, whereas the fauna from Dover is less rich in taxa and less abundant. In the German basinal sections, a morphogroup analysis of agglutinated foraminifera and the calculated diversities imply normal marine settings and oligotrophic to mesotrophic bottom-water conditions. Furthermore, acmes of agglutinated foraminifera correlate between different sections and can be used for paleoenvironmental analysis. Three acmes of the species Ammolagena contorta are recorded for the Turonian–Coniacian (perplexus to lower striatoconcentricus zones, lower scupini Zone, and hannovrensis Zone) and likely imply a shift to more oligotrophic bottom-water conditions. In the upper scupini Zone below the Turonian–Coniacian boundary, an acme of Bulbobaculites problematicus likely indicates enhanced nutrient availability. In general, agglutinated foraminiferal morphogroups display a gradual shift from Turonian oligotrophic environments towards more mesotrophic conditions in the latest Turonian and Coniacian.
Background In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function. Methods Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child’s immunisation booklet containing records of birth weight and serial weights in the first year. Results 2373 children participated, 52% girls, median age (IQR), 10 years (8–13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms ‘wheeze in the last 12 months’; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and ‘trouble breathing’ 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (β) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008 and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027. Conclusion These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.
Highway pavements deteriorate over time as successive wheel loads cause rutting, cracking, texture loss, and so forth. Design standards and pavement performance models account for some of the known contributory factors, such as levels of traffic and vehicle composition. However, such models are limited in their predictive power, and highway authorities must conduct regular pavement condition surveys rather than relying on the standard deterioration models alone. The ways in which multiple factors affect pavement deterioration, including rutting, are complex and are believed to include feedback loops where rutting then influences driving position, exacerbating the rutting levels. Standard regression models are not well suited to representing such complex causal mechanisms. This paper compares two alternative modeling approaches, structural equation models and auto-machine learning, and evaluates the predictive ability and practicalities of each. The findings indicate that auto-machine learning (AutoML) may be superior in its predictive ability. However, the “black box” nature of AutoML results makes them potentially less useful to practitioners. A process of using machine learning to help inform a structural equation model is proposed.
Introduction Polycystic liver disease (PLD) is a rare genetic disease of the liver that can significantly affect quality of life (QoL) of patients and cause serious complications. The PLD-specific Questionnaire (PLD-Q) score (which can vary from 0 to 100) can objectively assess severity of PLD-related symptoms. We wished to assess whether PLD-Q scores varied between different demographic groups with PLD. Aims We investigated gender-based variations in the disease in terms of symptom burden, age of diagnosis, cyst characteristics (number and size of liver cysts assessed radiologically) and frequency of complications (abdominal hernias, cyst rupture and/or haemorrhage, cyst infections). Methods We calculated PLD-Q scores in 47 fully phenotyped PLD patients, where 30 were females and 17 were males. We also determined the age of PLD diagnosis from available records in the two groups. We further compared radiological characteristics including Qian’s grade (based on number of liver cysts) and presence of dominant cyst(s)( cyst size >8 cm), between the two genders and the rate of complications. Results The mean PLD-Q score in women was 41.1 while the median was 39.5. The mean PLD-Q score in men was 24.9 with a median score of 26. The mean PLD-Q score in women was higher than that in men by 16.2 and the difference was highly statistically significant (p=0.0031 at 95% CI, using two-tailed independent sample t-test). The mean age of PLD diagnosis in women was 48 years which was 9.8 years earlier than that in men (57.8 years) (p=0.032 at 95% CI, using two-tailed independent sample t-test).Of 27 female patients, 4 (~15%) had Qian’s Grade 2 disease (11–20 liver cysts), 13 (~48%) had Grade 3 cysts (>20 cysts) while 10 (~37%) had Grade 4 cysts (>20 cysts with symptomatic hepatomegaly). In the male group of 13 patients, the respective numbers were 3 (~23%), 9 (69%) and 1 (8%). With regards to complications, 10 out of 30 female patients (33.33%) had at least one complication while 6 out of 18 male patients (33.33%) had the same. Discussion Our data suggests that women with PLD tend to have more severe symptoms and are diagnosed at an earlier age compared to men. Grade 4 liver cysts are much more common in women. Interestingly, the disease seems to have the same frequency of complications in the two genders in our study population.
Chronological age classifies elite male gymnasts into developmental performance classifications: senior (18+ years), junior (14-18 years) and development (8-14 years). Here, we examine the influence of age and experience on the biomechanics of the high bar longswing across classifications. Joint angular kinematics and kinetics were obtained from 30 gymnasts performing three sets each of eight consecutive longswings. Differences between groups and relations between age, experience and key biomechanical variables were correlated. Kinetic variables and range of motion of the hip and knee were highest for development gymnasts. In all age groups, a dominant shoulder kinetic contribution was found, although circle location of the peak joint kinetics occurred earliest for junior gymnasts. Hip work contributed more prominently in development gymnasts. Age and experience were positively correlated to an increase in peak shoulder moments and powers and negatively correlated to peak hip and knee moments. The findings reveal that age and experience combine to influence the functional phase, joint kinematics and relative joint kinetic contribution, particularly with the senior group demonstrating a shoulder dominant technique. Changes in musculoskeletal loading across the age groups suggest that factors such as relative strength and practice may have influenced this joint mode transition of the longswing. ARTICLE HISTORY
Abstract Background Very little data is available about the involvement of lifeboat crews in medical emergencies at sea. The aim of this study is to analyze the medical operations at sea performed by the Royal Netherlands Sea Rescue Institution (KNRM). Methods This is a retrospective descriptive analysis of all medical operations at sea performed by the KNRM between January 2017 and January 2020. The operations were divided in three groups: with ambulance crew aboard the lifeboat, ambulance crew on land waiting for the arrival of the lifeboat, and autonomous operations (without ambulance crew involvement). The main outcome measures were circumstances, encountered medical problems, follow-up and crew departure time. Results The KNRM performed 282 medical operations, involving 361 persons. Operations with ambulance crew aboard the lifeboat (n = 39; 42 persons) consisted mainly of persons with serious trauma or injuries; 32 persons (76.2%) were transported to a hospital. Operations with ambulance crew on land (n = 153; 188 persons) mainly consisted of situations where time was essential, such as persons who were still in the water, with risk of drowning (n = 45, 23.9%), on-going resuscitations (n = 9, 4.8%) or suicide attempts (n = 7, 3.7%). 101 persons (53,7%) were transported to a hospital. All persons involved in the autonomous operations (n = 90; 131 persons) had minor injuries. 38 persons (29%) needed additional medical care, mainly for (suspected) fractures or stitches. In 115 (40.8%) of all operations lifeboat crews did not know that there was a medical problem at the time of departure. Crew departure time in operations with ambulance crew aboard the lifeboat (13.7 min, min. 0, max. 25, SD 5.74 min.) was significantly longer than in operations with ambulance crew on land (7.7 min, min. 0, max 21, SD 4.82 min., p
Climate change and its consequences are the most important issues affecting the UK economy over the coming century and will present a critical challenge for the UK government moving forward. In particular, the challenge of getting to net zero by 2050 is going to have major ramifications for the macroeconomy. In this commentary, I lay out some of the work that has been done on the implications of climate change and the transition to net zero for the macroeconomy. Economic activity as currently structured involves using fossil fuels as part of the production process. But this releases carbon dioxide into the atmosphere and leads to higher temperatures. I take this as given, simply noting that if this rise in temperature and the change in weather patterns associated with it are going to be stopped, if not reversed, at some point in the future, then we have to move to a ‘net zero’ (or even ‘net negative’) economy in which output is produced using only those inputs which do not produce greenhouse gases.
Virtual reality (VR) research has provided overviews of locomotion techniques, how they work, their strengths and overall user experience. Considerable research has investigated new methodologies, particularly machine learning to develop redirection algorithms. To best support the development of redirection algorithms through machine learning, we must understand how best to replicate human navigation and behaviour in VR, which can be supported by the accumulation of results produced through live-user experiments. However, it can be difficult to identify, select and compare relevant research without a pre-existing framework in an ever-growing research field. Therefore, this work aimed to facilitate the ongoing structuring and comparison of the VR-based natural walking literature by providing a standardised framework for researchers to utilise. We applied thematic analysis to study methodology descriptions from 140 VR-based papers that contained live-user experiments. From this analysis, we developed the LoCoMoTe framework with three themes: navigational decisions, technique implementation, and modalities. The LoCoMoTe framework provides a standardised approach to structuring and comparing experimental conditions. The framework should be continually updated to categorise and systematise knowledge and aid in identifying research gaps and discussions.
Performance and energy are the two most important objectives for optimization on heterogeneous high performance computing platforms. This work studies a mathematical problem motivated by the bi‐objective optimization of data‐parallel applications on such platforms for performance and energy. First, we formulate the problem and present an exact algorithm of polynomial complexity solving the problem where all the application profiles of objective type one are continuous and strictly increasing, and all the application profiles of objective type two are linear increasing. We then apply the algorithm to develop solutions for two related optimization problems of parallel applications on heterogeneous hybrid platforms, one for performance and dynamic energy and the other for performance and total energy. Our proposed solution methods are then employed to solve the two bi‐objective optimization problems for two data‐parallel applications, matrix multiplication and gene sequencing, on a hybrid platform employing five heterogeneous processors, namely, two different Intel multicore CPUs, an Nvidia K40c GPU, an Nvidia P100 PCIe GPU, and an Intel Xeon Phi.
Iatrogenic urinary tract injury (IUTI) is a severe complication of emergency digestive surgery. It can lead to increased postoperative morbidity and mortality and have a long-term impact on the quality of life. The reported incidence of IUTIs varies greatly among the studies, ranging from 0.3 to 1.5%. Given the high volume of emergency digestive surgery performed worldwide, there is a need for well-defined and effective strategies to prevent and manage IUTIs. Currently, there is a lack of consensus regarding the prevention, detection, and management of IUTIs in the emergency setting. The present guidelines, promoted by the World Society of Emergency Surgery (WSES), were developed following a systematic review of the literature and an international expert panel discussion. The primary aim of these WSES guidelines is to provide evidence-based recommendations to support clinicians and surgeons in the prevention, detection, and management of IUTIs during emergency digestive surgery. The following key aspects were considered: (1) effectiveness of preventive interventions for IUTIs during emergency digestive surgery; (2) intra-operative detection of IUTIs and appropriate management strategies; (3) postoperative detection of IUTIs and appropriate management strategies and timing; and (4) effectiveness of antibiotic therapy (including type and duration) in case of IUTIs.
The much we know about the mental health of internally displaced persons (IDPs) today comes from studies conducted with IDPs who stay in displacement camps. Little is known about IDPs’ mental health and experiences living outside the camps. This qualitative study explored the lived experiences of IDPs living outside displacement camps in Nigeria. Participants were eight IDPs ( M age = 36, SD = 1.6) selected from villages in Benue, Nigeria. Data were gathered through semi-structured interviews and studied using a hermeneutic phenomenological approach. Overarching themes from the data analysis suggested regret, worry, anxiety, prolonged grief, suicidal ideation, depression, and cumulative trauma. Collectively, these themes indicate the possible presence or emergence of psychopathologies. The findings from the study point to the urgent and compelling need for targeted mental health services for not just IDPs within displacement camps but also those who stay outside the displacement camps.
This article focuses on the English Early Childhood Education and Care (ECEC) sector’s perception of graduates in the workforce. Previous research has already highlighted the benefits of a graduate workforce, demonstrating a positive impact on provision and leading to high-quality education and care. However, there has been limited appetite for policy makers to reflect the wider need for graduates in non-compulsory provision. This research aimed to explore the ECEC sector’s perspectives on: higher education (HE) qualifications on the skills and knowledge graduates’ need to develop, both in training and in practice, to provide high-quality ECEC provision. Employing qualitative research approaches via survey (n = 105) and semi-structured interview (n = 16) methods, data were collected from ECEC owners, managers and practitioners. Our findings indicate the importance of HE qualifications as they give a sound foundational knowledge of child development and behaviour management to future staff; develop students’ and graduates reflective skills about their own, and others’ professional practice; support development of business management skills; and enhance further understanding and knowledge of how to interpret current legislation. The findings inform the understanding of the ways in which HE programmes can enable practitioners to develop themselves and contribute to their wider profession.
This study examines whether corporate commitment to climate change is driven by country-level factors related to cultural values and the legal system (LS) of a country. We also investigate the impact of corporate governance strength on climate change commitment and the extent to which there are moderating effects between corporate governance and cultural and LS influences. We use a large dataset of 21,564 firm-year observations of companies operating in the United States, UK, and China for the period 2013 to 2020 and develop a unique measure for climate change commitment using different proxies for measuring climate change practices. We find variations in climate change commitment among the three countries and that cultural values and LSs affect corporate commitment to climate change. Companies located in a socially oriented society, which are transparent and characterized by long-term orientation, are more strongly involved in climate change actions. The strength of corporate governance increases corporate commitment to climate change. Corporate governance also moderates some of the detrimental cultural influences on climate change commitment. These findings have implications for managers as they reveal that macro-level factors affect behavior and that corporate governance can help to moderate these factors.
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