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Shears, being everyday objects, have received significantly less attention by archaeometallurgists than other edged tools or weapons. Yet, shear blades were forged with the same techniques as blades of, e.g. knives and swords. The most common shear type in ancient times was the bow shears, where the bow had to be flexible so it could be repeatedly bent without cracking or breaking. The shear-maker, therefore, faced the challenge of combining hard steel (the blades) with soft/flexible steel (the bow). In fact, bow shears are one of the first tools to be invented, where metal acts as a spring. Thus, ancient bow shears can be used for investigating the history and development of spring steel technology, which is currently unclear. Here, we present the metallurgical characterization of two 11th–12th c. single-bow shears from Sigtuna, Sweden. Both the blades and the bows of the two shears were found to be of decent quality and much better than in older shears from the Roman period. Although the steel qualities are not quite up to modern standards, this does not in itself prove that the Sigtuna blacksmiths lacked the technological knowledge to make ideal spring steel. Shears are relatively cheap everyday objects intended to be used until they break, at which point they are discarded. Therefore, it might not have been worth the Medieval blacksmiths’ time and effort to perfect the material properties of steel used in shears. The shears’ blades are on par with Medieval-period knife blades, and future studies on ancient shear-making should preferably involve comparisons of shears and knives from the same origins.

Aims Cardiovascular risk factor control fluctuates, tends to change over time, and is potentially impacted by multifactorial interactions. Currently, the presence of risk factors, rather than their variability or interplay with one another, is taken into account to define the population at risk. The association between variability of risk factors and cardiovascular morbidity and mortality risk among patients with Type 2 diabetes mellitus (T2DM) remains debatable. Methods and results Using registry-derived data, we identified 29 471 people with T2DM, without cardiovascular disease (CVD) at baseline, and with at least five measurements of risk factors. Variability for each variable was expressed as quartiles of the standard deviation during 3 years (exposure). The incidence of myocardial infarction, stroke, and all-cause mortality was assessed during 4.80 (2.40–6.70) years following the exposure phase. The association between the measures of variability and the risk of developing the outcome was investigated through multivariable Cox proportional-hazards regression analysis with stepwise variable selection. Then, the recursive partitioning and amalgamation (RECPAM) algorithm was used to explore the interaction among the variability of risk factors associated with the outcome. An association between the variability of HbA1c, body weight, systolic blood pressure, and total cholesterol with the outcome considered was found. Among the six classes of risk identified by RECPAM, patients with a high variability of both body weight and blood pressure had the highest risk [Class 6, hazard ratio (HR) = 1.81; 95% confidence interval (CI) 1.61–2.05] compared with patients with low variability of both body weight and total cholesterol (Class 1, reference), despite a progressive reduction in the mean level of risk factors during successive visits. Individuals with high weight variability but low–moderate systolic blood pressure variability (Class 5, HR = 1.57; 95% CI 1.28–1.68), patients with moderate/high weight variability associated with high/very high HbA1c variability (Class 4, HR = 1.33; 95% CI 1.20–1.49), subjects with moderate/high weight variability and with low/moderate HbA1c variability (Class 3, HR = 1.12; 95% CI 1.00–1.25), as well as those with low weight variability associated with high/very high total cholesterol variability (Class 2, HR = 1.14; 95% CI 1.00–1.30) also showed a significant increase in the risk of an event. Conclusion Combined high variability of two risk factors, particularly body weight and blood pressure, is associated with cardiovascular risk among patients with T2DM. These findings highlight the importance of continuous balancing of multiple risk factors.

Purpose Suboptimal adherence to adjuvant endocrine treatment (AET) is an important clinical concern. A correlation between CYP2D6 activity and tamoxifen discontinuation has been described. The main aim of this study was to investigate the consistency between pharmacy dispensation data and medical records on adherence to AET. Methods Adherence was calculated for patients with at least 4.5 years of follow up and was defined as Medical Possession Rate ≥ 80%. Subgroup analyses were performed based on menopausal status, recurrence risk and CYP2D6 activity. Results In 86% of the 1235 included patients the consistency between the two sources of information was within 80–125%. Poor consistency, Conclusions There was a good consistency between medical records and pharmacy dispensing data on the use of AET. Adherence to AET was adequate, especially when including switch to aromatase inhibitors. Surprisingly, CYP2D6 PMs had low adherence to tamoxifen, despite a likely reduced risk of side effects according to previous data.

We demonstrate that measurements obtained from NASA’s magnetospheric multiscale (MMS) mission support quasi-adiabatic electron heating in quasi-perpendicular shocks with temperature Te⊥ ∝ B1 + α, where B is the magnetic field strength and α represents departure from adiabaticity. Adiabatic heating (α = 0) results from the conservation of magnetic moment on spatially increasing magnetic field inside the shock ramp. Negative α < 0 is observed in most situations, where perpendicular energy gain from adiabatic heating is redistributed by interactions with waves to the parallel direction leading to a lower isotropic temperature increase. Positive α is observed when the stochastic heating of electrons is activated by the E × B wave acceleration mechanism by electrostatic waves leading to a higher temperature increase. By using test-particle simulations in a realistic shock model we have elucidated the process of stochastic wave acceleration. We have also shown the equivalence of adiabatic heating and acceleration by gradient B drift at shocks with low Mach numbers and demonstrated that the cross-shock potential does not contribute to the electron heating. Signatures of quasi-adiabatic heating and/or stochastic heating of electrons are observed in all shocks analysed with measurements by the MMS.

Most modern studies of Swedish phonology take the view that the underlying vowel inventory of Central Standard Swedish comprises nine, rather than seventeen or eighteen, mutually contrasting vowel phonemes. A residual problem of a classic phonological type concerns the borrowed entities, rendered in traditional Swedish orthography as au and eu, whose ‘status in the vowel system is unclear’ (Riad 2014:42). The present paper scrutinizes earlier and current phonological interpretations of these entities, adduces evidence for and against each proposal, and concludes that the case for treating them as phonemic diphthongs /V͡V/, as /VC/-sequences, or as monosyllabic /VV̯/-sequences is weak and that they should in the first place be viewed as underlying heterosyllabic vowel sequences /VV/, subject to a special phonological stipulation valid for a borrowed sub-domain of the lexicon. Typologically, Central Standard Swedish should continue to be subsumed under the category of languages that lack phonological diphthongs.

We estimate static and dynamic agglomeration effects on earnings among university graduates using Swedish longitudinal population register data. The prime interest lies with whether and how the dynamic effects of big city work experience vary by observed ability of workers and whether the effects are portable after relocation. Urban wage premium and spatial sorting of university graduates are analysed by using information on school grades, parental education and university rank. We find that the value of accumulated big city work experience increases with observed ability. The dynamic premium of working in bigger cities is not lost when moving to smaller cities, suggesting that it reflects learning effects and human capital accumulation. Our findings indicate systematic spatial sorting on observed indicators of ability as well as on unobserved productive traits. Sorting on unobserved abilities is driven primarily by graduates in the upper part of the observed ability distribution and is apparent also when taking dynamic learning effects into consideration.

This study examines news media framing of the opioid crisis in Canada to advance an understanding of the dominant discourses and identify the narratives shaping public and policymakers’ opinions and preferred solutions. We conducted a content and frame analysis of 2,273 Canadian news articles published between January 2016 and December 2019. The analysis revealed that harm reduction and treatment were the preferred solutions instead of criminalization, and public health framing predominantly occurred. The overall tone emerged as empathetic and softer and, generally, the leading policy choices and opioid crisis were framed contradistinct from past drug epidemics.

OBJECTIVE To investigate trends, optimal levels for cardiometabolic risk factors, and multifactorial risk control in diabetic nephropathy and end-stage kidney disease (ESKD) in patients with diabetes and matched control subjects. RESEARCH DESIGN AND METHODS This study included 701,622 patients with diabetes from the Swedish National Diabetes Register and 2,738,137 control subjects. Trends were analyzed with standardized incidence rates. Cox regression was used to assess excess risk, optimal risk factor levels, and risk according to the number of risk factors, in diabetes. RESULTS ESKD incidence among patients with and without diabetes initially declined until 2007 and increased thereafter, whereas diabetic nephropathy decreased throughout follow-up. In patients with diabetes, baseline values for glycated hemoglobin, systolic blood pressure (SBP), triglycerides, and BMI were associated with outcomes. Hazard ratio (HR) for ESKD for patients with type 2 diabetes who had all included risk factors at target was 1.60 (95% CI 1.49–1.71) compared with control subjects and for patients with type 1 diabetes 6.10 (95% CI 4.69–7.93). Risk for outcomes increased in a stepwise fashion for each risk factor not at target. Excess risk for ESKD in type 2 diabetes showed a HR of 2.32 (95% CI 2.30–2.35) and in type 1 diabetes 10.92 (95% CI 10.15–11.75), compared with control. CONCLUSIONS Incidence of diabetic nephropathy has declined substantially, whereas ESKD incidence has increased. Traditional and modifiable risk factors below target levels were associated with lower risks for outcomes, particularly notable for the causal risk factors of SBP and HbA1c, with potential implications for care.

Background: The role of diabetes in the development of valvular heart disease, and, in particular, the relation with risk factor control, has not been extensively studied. Methods: We included 715 143 patients with diabetes registered in the Swedish National Diabetes Register and compared them with 2 732 333 matched controls randomly selected from the general population. First, trends were analyzed with incidence rates and Cox regression, which was also used to assess diabetes as a risk factor compared with controls, and, second, separately in patients with diabetes according to the presence of 5 risk factors. Results: The incidence of valvular outcomes is increasing among patients with diabetes and the general population. In type 2 diabetes, systolic blood pressure, body mass index, and renal function were associated with valvular lesions. Hazard ratios for patients with type 2 diabetes who had nearly all risk factors within target ranges, compared with controls, were as follows: aortic stenosis 1.34 (95% CI, 1.31–1.38), aortic regurgitation 0.67 (95% CI, 0.64–0.70), mitral stenosis 1.95 (95% CI, 1.76–2.20), and mitral regurgitation 0.82 (95% CI, 0.79–0.85). Hazard ratios for patients with type 1 diabetes and nearly optimal risk factor control were as follows: aortic stenosis 2.01 (95% CI, 1.58–2.56), aortic regurgitation 0.63 (95% CI, 0.43–0.94), and mitral stenosis 3.47 (95% CI, 1.37–8.84). Excess risk in patients with type 2 diabetes for stenotic lesions showed hazard ratios for aortic stenosis 1.62 (95% CI, 1.59–1.65), mitral stenosis 2.28 (95% CI, 2.08–2.50), and excess risk in patients with type 1 diabetes showed hazard ratios of 2.59 (95% CI, 2.21–3.05) and 11.43 (95% CI, 6.18–21.15), respectively. Risk for aortic and mitral regurgitation was lower in type 2 diabetes: 0.81 (95% CI, 0.78–0.84) and 0.95 (95% CI, 0.92–0.98), respectively. Conclusions: Individuals with type 1 and 2 diabetes have greater risk for stenotic lesions, whereas risk for valvular regurgitation was lower in patients with type 2 diabetes. Patients with well-controlled cardiovascular risk factors continued to display higher risk for valvular stenosis, without a clear stepwise decrease in risk between various degrees of risk factor control.

Introduction A post hoc analysis of the PIONEER 1–5 and 8 trials assessed the clinically relevant composite endpoints of HbA1c (glycated haemoglobin) reduction ≥ 1% and body weight loss of ≥ 5% or ≥ 10% with orally administered semaglutide versus comparators. Methods In the PIONEER trials, people with type 2 diabetes were randomised to orally administered semaglutide versus placebo (PIONEER 1, 4, 5 and 8), empagliflozin (PIONEER 2), sitagliptin (PIONEER 3) and liraglutide (PIONEER 4) for 26–78 weeks. This analysis assessed the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% at week 26 and at end of treatment, and the proportion of people achieving an HbA1c reduction of ≥ 1% and body weight loss of ≥ 10% at end of treatment. Results Overall, 3506 people in PIONEER 1–5 and 8 were included. At week 26 and at end of treatment, odds of achieving the composite endpoint of an HbA1c reduction of ≥ 1% and body weight loss of ≥ 5% were significantly greater with orally administered semaglutide 14 mg than with placebo (PIONEER 1, 4, 5 and 8; all p

This paper presents the third edition of the CM SAF cLoud, Albedo and surface RAdiation dataset from AVHRR data, CLARA-A3. The content of earlier CLARA editions, namely cloud, surface albedo, and surface radiation products, has been extended with two additional surface albedo products (blue and white sky albedo), three additional surface radiation products (net shortwave and longwave radiation, surface radiation budget) and two top of atmosphere radiation budget products (reflected solar flux and outgoing longwave radiation). The record length is extended to 42 years (1979–2020) by also incorporating results from the first version of the Advanced Very High Resolution Radiometer (AVHRR) imager (AVHRR/1). A continuous extension of the climate data record (CDR) has also been implemented by processing an interim climate data record (ICDR) based on the same set of algorithms but with slightly changed ancillary input data. All products are briefly described together with validation results and inter-comparisons with currently existing similar CDRs. The extension of the product portfolio and the temporal coverage of the data record, together with product improvements, is expected to enlarge the potential of using CLARA-A3 for climate change studies and, in particular, studies of potential feedback effects between clouds, surface albedo and radiation. The CLARA-A3 data record is hosted by the European Organisation for the Exploitation of Meteorological Satellites (EUMETSAT) Satellite Application Facility on Climate Monitoring (CM SAF) and is freely available at https://doi.org/10.5676/EUM_SAF_CM/CLARA_AVHRR/V003.

Meteorological forecast models, notably snowfall predictions, require accurate knowledge of the properties of snow particles, such as their size, cross-sectional area, mass, shape, and fall speed. Therefore, measurements of individual snow particles’ fall speed and their cross-sectional area, from which a size parameter and area ratio can be derived, provide very useful datasets. We have compiled such a dataset from measurements with the Dual Ice Crystal Imager (D-ICI) in Kiruna during several winter seasons from 2014 to 2019. Using that data, we have previously studied shape-dependent relationships between fall speed and particle size, cross-sectional area, and particle mass. While we had used maximum dimension as the size parameter, we have found that it seems unsuitable for certain shapes like columnar particles. Here, we investigate which particle size parameter should be used depending on the shape or if one size parameter is suitable for all shapes. With a more suitable particle size parameter, we aim to improve the relationships between fall speed and particle size and mass.

BACKGROUND: The goal of this work was to investigate trends (2001–2019) for cardiovascular events and cardiometabolic risk factor levels in individuals with type 2 diabetes (T2D) and matched control subjects. METHODS: This study included 679 072 individuals with T2D from the Swedish National Diabetes Register and 2 643 800 matched control subjects. Incident outcomes comprised coronary artery disease, acute myocardial infarction, cerebrovascular disease, and heart failure (HF). Trends in time to first event for each outcome were analyzed with Cox regression and standardized incidence rates. In the group with T2D, Cox regression was also used to assess risk factor levels beyond target and outcomes, as well as the relative importance of each risk factor to each model. RESULTS: Among individuals with T2D, incidence rates per 10 000 person-years in 2001 and 2019 were as follows: acute myocardial infarction, 73.9 (95% CI, 65.4–86.8) and 41.0 (95% CI, 39.5–42.6); coronary artery disease, 205.1 (95% CI, 186.8–227.5) and 80.2 (95% CI, 78.2–82.3); cerebrovascular disease, 83.9 (95% CI, 73.6–98.5) and 46.2 (95% CI, 44.9–47.6); and HF, 98.3 (95% CI, 89.4–112.0) and 75.9 (95% CI, 74.4–77.5). The incidence for HF plateaued around 2013, a trend that then persisted. In individuals with T2D, glycated hemoglobin, systolic blood pressure, estimated glomerular filtration rate, and lipids were independently associated with outcomes. Body mass index alone potentially explained >30% of HF risk in T2D. For those with T2D with no risk factor beyond target, there was no excess cardiovascular risk compared with control subjects except for HF, with increased hazard with T2D even when no risk factor was above target (hazard ratio, 1.50 [95% CI, 1.35–1.67]). Risk for coronary artery disease and cerebrovascular disease increased in a stepwise fashion for each risk factor not within target. Glycated hemoglobin was most prognostically important for incident atherosclerotic events, as was body mass index for incident of HF. CONCLUSIONS: Risk and rates for atherosclerotic complications and HF are generally decreasing among individuals with T2D, although HF incidence has notably plateaued in recent years. Modifiable risk factors within target levels were associated with lower risks for outcomes. This was particularly notable for systolic blood pressure and glycated hemoglobin for atherosclerotic outcomes and body mass index for heart failure.

Born a Swedish farmer’s son, Claes Lagergren trained as a tradesman in Paris in the early 1870s. An unexpected inheritance made him financially independent and enabled him to begin his travels in Europe. Whilst in Rome, he converted to the Roman Catholic faith, an important step in a social career that rapidly introduced him to the upper echelons of Roman nobility – and particularly to those families that had stayed true to the Pope in the aftermath of the unification of Italy. Lagergren was introduced to the Papal court and to Pope Leo XII, who favoured him. Eventually, he was honoured with the title of marquis and became one of the Pope’s chamberlains. The Marquis was a diarist and published his memoirs in nine volumes in the 1920s. His writings are a barely explored source of his political and cultural views – and of his love for Versailles. During his many visits to the palace, informed by his reading of guidebooks and memoirs, he wrote about his sensations and experiences of the former royal site. Politically, Lagergren considered himself a legitimist who honoured the values of the Ancien Régime, and he treasured the Restoration. From this perspective, Versailles and its palace constituted a strong symbol and lieu de mémoire of pre-revolutionary Europe. In the early 1880s, Lagergren married the wealthy American Caroline Russell. The couple bought seventeenth-century Tyresö Castle, outside Stockholm − a home that Lagergren would bequeath to a Stockholm museum, the Nordiska museet, after his death in 1930. Tyresö became a place where Lagergren displayed his collections, in particular portraits of members of the French Bourbon dynasty that he had seen at Versailles. Né fils d’un paysan suédois, Claes Lagergren suit une formation de commerçant à Paris au début des années 1870. Un héritage inattendu le rend financièrement indépendant et lui permet d’effectuer plusieurs voyages en Europe. Pendant son séjour à Rome, il décide de se convertir à la foi catholique romaine, une étape importante dans une carrière sociale qui l’introduit rapidement dans les cercles de la noblesse romaine – et en particulier dans les familles restées fidèles au pape au lendemain de l’unification de l’Italie. Lagergren est présenté à la cour pontificale et au pape Léon XII qui le protège. Il est alors honoré du titre de marquis et devient l’un des chambellans du pape. Il est aussi chroniqueur et publie ses mémoires en neuf volumes dans les années 1920. Ses écrits sont une source presque inexplorée révélant ses opinions politiques et culturelles – mais aussi son amour pour Versailles. Au cours de ses nombreuses visites au palais, éclairé par sa lecture de guides et de mémoires, il relate ses sensations et ses expériences de l’ancien site royal. Politiquement, Lagergren se considérait comme un légitimiste qui honorait les valeurs de l’Ancien Régime et il chérissait la Restauration. Dans cette optique, Versailles et son palais constituaient un symbole fort et un lieu de mémoire de l’Europe prérévolutionnaire. Au début des années 1880, Lagergren épouse la riche américaine Caroline Russell. Le couple achète le château de Tyresö, datant du xviie siècle et situé à l’extérieur de Stockholm - une maison que Lagergren lèguera finalement au musée Nordiska après sa mort en 1930. Tyresö est devenu un lieu d’exposition de collections, en particulier des portraits des membres de la dynastie française des Bourbons que Lagergren avait vus à Versailles.

This narrative review describes a new approach to navigation in a challenging landscape of clinical drug development in diabetes. Successful outcome studies in recent years have led to new indications and guidelines in type 2 diabetes, yet the number of clinical trials in diabetes is now declining. This is due to many environmental factors acting in concert, including the prioritisation of funding for other diseases, high costs of large randomised clinical trials, increase in regulatory requirements and limited entry of novel candidate drugs. There is a need for novel and cost-effective paradigms of clinical development to meet these and other challenges. The concept of registry-based randomised clinical trials (RRCTs) is an attractive option. In this review we focus on type 2 diabetes and the prevention of cardiovascular and microvascular comorbidities and mortality, using the Swedish SMARTEST trial as an example of an RRCT. We also give some examples from other disease areas. The RRCT concept is a novel, cost-effective and scientifically sound approach for conducting large-scale diabetes trials in a real-world setting. Graphical abstract

To explore oral health by increasing degree of obesity and the influence of modifying factors.A cross-sectional design was used. Swedish females (Mean BMI was 42.2 kg/mYoung obese women exhibited poor oral health with higher caries levels by higher BMI. Dental care should adapt the prevention efforts for obese individuals.

To compare the participation attendance and involvement of children and young people with and without cerebral palsy (CP) in a low-resource area of Uganda.Eighty-two children and young people with CP aged 6 to 22 years (49 males, 33 females) and 81 age- and sex-matched peers without CP (6 to 22 years; 48 males, 33 females) participated in this population-based, cross-sectional study. Data on attendance and involvement in 20 home and community activities were obtained using Picture My Participation, an instrument intended to measure participation in children with disabilities, particularly in low- and middle-income countries. Non-parametric statistical methods were used to assess between-group differences. Effect size estimates were calculated.Pooled attendance across all activities was lower in children and young people with CP than in children and young people without CP (p 0.001) and for each activity item (p = 0.004 to p 0.001). The effect sizes for each activity were 0.2 to 0.7. Between-group differences were larger for community activities than for home activities. Pooled involvement across all activities was less in the group with CP (p 0.001) and for each activity (p = 0.014 to p 0.001). The effect sizes for each activity were 0.2 to 0.5. Children and young people in Gross Motor Function Classification System (GMFCS) levels I and II had higher attendance (p 0.001) and involvement (p = 0.023) than those in GMFCS levels III to V.Participation of young people living with CP in Uganda was restricted, especially for community activities. There is a need to identify context-specific participation barriers and develop strategies to overcome them.

This study explores features of food system transformations towards sustainability in the Farm to Fork Strategy in relation to perspectives of Swedish food system practitioners. Transformations towards sustainable food systems are essential to achieve the United Nations’ 2030 Agenda and the need for more sustainable food systems has been recognised in the European Green Deal and its Farm to Fork Strategy. The Swedish ambition to act as a global leader in achieving the 2030 Agenda and the European Commission’s aspiration for Europe to lead global food system transformations offer a critical opportunity to study transformational processes and agents of change in a high-income region with externalised environmental and sustainability impacts. Drawing on theories of complex systems transformations, this study identifies features of food system transformations, exploring places to intervene and examines the roles, responsibilities, and agency related to these changes. The results of this study provide three main conclusions highlighting (i) alignment of high-level policy and the perspectives of national practitioners at the paradigm level, especially concerning how food is valued, which is a crucial first step for transformational processes to come about (ii) a lack of clarity as well as diversity of pathways to transform food systems although common objectives are expressed, and (iii) governance mechanisms as enablers for a diversity of transformations. Moreover, these processes must acknowledge the contextual and complex nature of food systems and the level of agency and power of actors.

Objectives To evaluate the effects of weight loss treatment on physical fitness in patients with psoriatic arthritis (PsA) and obesity compared to matched controls. Methods In total, 46 patients with PsA (CASPAR) and BMI ≥ 33 kg/m2 and 52 obese persons were included in this 12-month prospective open intervention study with a very low energy diet (640 kcal/day), followed by structured reintroduction of an energy-restricted diet and brief support for physical activity. The primary outcome was muscle strength assessed with hand-grip strength (Grippit) and leg muscle strength (timed stand test). Secondary outcomes were cardiorespiratory fitness, body composition, and physical functioning (SF-36PCS). Outcomes were assessed at baseline, 6 (M6), and 12 months (M12). Nonparametric statistics were used. Results Median weight reduction at M6 was 18.9 kg in patients and 23.0 kg in controls, (p = 0.546). At M12, patients’ median weight loss from baseline was 16.1 kg, corresponding with significant loss of total fat mass (− 30.1%), and lean mass (total − 7.0%, arm − 13.7%, and leg − 6.0%). Leg muscle strength improved in patients and controls at M6 (p p p = 0.018) and M12 (p = 0.028) but not in patients. Physical functioning improved in both groups at M6 (p p = 0.008) and (p Conclusion The intervention resulted in positive effects on body weight and total body fat. Despite reduced lean body mass, the muscle strength did not deteriorate in patients with PsA and controls. Trial registration ClinicalTrials.gov identifier: NCT02917434, registered on September 21, 2016-retrospectively registered. Key Points• Patients with PsA and obesity can benefit from weight loss treatment without the risk of deterioration in muscle strength and cardiorespiratory fitness.• Muscle strength and cardiorespiratory fitness were below suggested normative values for the majority of the patients at all time points, implying that more structured exercise strategies might be warranted to counteract physical fitness deficiencies in patients with PsA undergoing weight loss treatment.

Background Validated outcome measures are essential for assessment and treatment of children with disabilities. The Children’s Hand-use Experience Questionnaire (CHEQ) was developed and validated for use in Western countries for children with unilateral hand dysfunction. This study aimed to perform a cross-cultural adaptation and investigate reliability for the Arabic CHEQ. Methods Translation and cross-cultural adaptation were performed in four phases: (i) forward-translation and reconciliation with feedback from parents and typically developing children from Jordan ( n = 14); (ii) backward-translation and review; (iii) cognitive debriefing with parents and/or their children with unilateral hand dysfunction ( n = 17); and (iv) review and proofreading. In the psychometric analyses, 161 children from Jordan (mean age [SD] 10y 8 m [5y 8 m]; 88 males) participated. Internal consistency was evaluated with Cronbach’s alpha. Test-retest reliability was evaluated in 39 children with intraclass correlation coefficient (ICC) and weighted kappa (κ). Results Synonyms of four words were added to accommodate for different Arabic dialects. On average, 93% of children with unilateral hand dysfunction and their parents understood the CHEQ items. One response alternative, ‘ Get help’, to the opening question was unclear for 70% of the respondents and need further explanation. Two items about using a knife and fork were difficult to comprehend and culturally irrelevant. High internal consistency was demonstrated (Cronbach’s alphas 0.94- 0.97) and moderate to excellent ICC (0.77–0.93). For 18 individual items, κ indicated poor to good agreement (κ between 0.28 and 0.66). Conclusions After the suggested minor adjustments, the Arabic CHEQ will be comprehensible, culturally relevant and reliable for assessing children with unilateral hand dysfunction in Jordan.

PurposeSpecifically, the authors discuss three challenges that researchers—especially graduate students—often face: (1) access to adequate material and guidance for researchers; (2) the internal and external strains researchers may face, and (3) the limited conceptualization of research on sensitive topics or vulnerable populations. Although these three challenges may be present for many graduate students and junior scholars, it is important to acknowledge that scholars face many challenges beyond the ones discussed in this note.Design/methodology/approachThis note will specifically address challenges that arise for graduate students and junior scholars, and we suggest possible strategies to navigate this type of research.FindingsThe authors encourage comprehensive approaches taken by institutions, enacted via advocacy from the field. Professional organizations can create a valuable, ongoing forum for such discussions by including the topic of researcher trauma within workshops, discussion sessions, conference tracks, journals, and newsletters. Second, the topic of researcher trauma must be introduced early and often in graduate training, including planned meaningful coverage in methodology courses, textbooks, and professional training. Third, researchers at all levels should carefully reflect on how their own line of inquiry and their routine research practices could impart trauma.Originality/valueWhile ethical principles center on protecting human research participants, risks of trauma experienced by researchers are not consistently addressed in the context of methodological training or human-subjects internal review board and ethics committees' consideration. Although many researchers engage in work that can cause the researcher trauma, few studies address the experiences of researchers in depth, especially the experiences of graduate students or junior scholars.

An innovative design process which has been conducted under the restrictions during the covid-19 pandemic is in focus in this study. Visits were banned so user-centred design activities were particularly challenged by the necessity to meet and work online. The purpose of the study is to present and reflect on how user-centred design was done under those conditions. The potential users, the reindeer herders, were merely contacted online, the user investigation were supported by for example using videos and storytelling. Also, the final concept is presented.

Supplementary Figure Legends 1-4 from Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

Supplementary Figure 2 from Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

Supplementary Figure 4 from Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

Supplementary Figure 3 from Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

Supplementary Table 1 from Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

“Mitocans” from the vitamin E group of selective anticancer drugs, α-tocopheryl succinate (α-TOS) and its ether analogue α-TEA, triggered apoptosis in proliferating but not arrested endothelial cells. Angiogenic endothelial cells exposed to the vitamin E analogues, unlike their arrested counterparts, readily accumulated reactive oxygen species (ROS) by interfering with the mitochondrial redox chain and activating the intrinsic apoptotic pathway. The vitamin E analogues inhibited angiogenesis in vitro as assessed using the “wound-healing” and “tube-forming” models. Endothelial cells deficient in mitochondrial DNA (mtDNA) were resistant to the vitamin E analogues, both in ROS accumulation and apoptosis induction, maintaining their angiogenic potential. α-TOS inhibited angiogenesis in a mouse cancer model, as documented by ultrasound imaging. We conclude that vitamin E analogues selectively kill angiogenic endothelial cells, suppressing tumor growth, which has intriguing clinical implications. [Cancer Res 2007;67(24):11906–13]

Supplementary Figure 1 from Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress

Extensive scholarship has previously explored how police officers perceive crime victims. For example, scholars argue that victims’ behavior, relationship with the offender, and level of intoxication impact how officers perceive victims. Although this research explores several aspects of officers’ perception of victims, few studies have specifically explored in-depth police officers’ empathy toward victims. This article explores how officers perceive empathy and for what types of victims officers describe having the most and least empathy. Specifically, this article examines what types of crimes, characteristics of the victim, and contextual factors officers describe as impacting their level of empathy toward victims. Qualitative analysis was conducted on 25 interviews with police officers working in the greater Washington, DC area. Findings suggest that officers perceive innocence as something that informs their empathy toward victims. Officers used the examples of children and “criminals” to explain that victims who are perceived as more innocent receive more empathy than victims who are perceived as less innocent.

Contemporary approaches to the treatment of chronic illness in mainstream healthcare services require long-term specialist support that attend to specific health complaints rather than the multi-faceted individual case presentation. However, treatment outcomes are often poor, treatment engagement is deficient, and longitudinal efficacy is typically variable. The Läklabbet Healing Lab utilized a single-arm non-randomised pilot study design comprising multiple integrative interventions targeted at improving general wellbeing and health markers for a demographic of people with diffuse diagnoses, that had been unable to work for a period of over one-year despite conventional primary care treatment. A total of N = 6 participants were recruited to the Healing Lab, presenting with varied, multiple and complex health complaints, all of whom were female. All participants completed the intervention programme (Timepoint 2), and no participants were lost to follow up. Symptom tracking subjective rating scores at each timepoint demonstrated overall global improvement across all domains in all participants. Cognitive improvement was also observed in continuous performance testing (QIK Test CPT) outcomes. The collaborative multidisciplinary working practices augmented the therapeutic climate for change through interdisciplinary communication and continuity of care; methodology that promoted the value of collaborative inquiry and case formulation is discussed in this paper.

Type 2 diabetes (T2D) develops due to insulin resistance and an inability of the pancreatic β-cells to increase secretion of insulin and reduce elevated blood glucose levels. Diminished β-cell function and mass have been implicated in impaired β-cell secretory capacity and several microRNAs (miRNAs) have been reported to be involved in regulating β-cell processes. We believe miRNAs are nodes in important miRNA-mRNA networks regulating β-cell function and that miRNAs therefore can be targets for the treatment of T2D. MicroRNAs are short (≈19-23 nucleotides [nt]) endogenous noncoding RNAs which regulate gene expression by directly binding to the mRNA of their target genes. Under normal circumstances, miRNAs act as rheostats to keep expression of their gene targets at optimal levels for different β-cell outputs. In T2D, levels of some miRNAs are altered as part of the compensatory mechanism to improve insulin secretion. Other miRNAs are differentially expressed as part of the process of T2D pathogenesis, which results in reduced insulin secretion and increased blood glucose. In this review, we present recent findings concerning miRNAs in islets and in insulin-secreting cells, and their differential expression in diabetes, with a specific focus on miRNAs involved in β-cell apoptosis/proliferation and glucose-stimulated insulin secretion. We present thoughts around miRNA-mRNA networks and miRNAs as both therapeutic targets to improve insulin secretion and as circulating biomarkers of diabetes. Overall, we hope to convince you that miRNAs in β-cells are essential for regulating β-cell function and can in the future be of clinical use in the treatment and/or prevention of diabetes.

Background Genetic variability in the cytochrome P450 CYP2C9 constitutes an important predictor for efficacy and safety of various commonly prescribed drugs, including coumarin anticoagulants, phenytoin and multiple non-steroidal anti-inflammatory drugs (NSAIDs). A global map of CYP2C9 variability and its inferred functional consequences has been lacking. Results Frequencies of eight functionally relevant CYP2C9 alleles (*2, *3, *5, *6, *8, *11, *13 and *14) were analyzed. In total, 108 original articles were identified that included genotype data from a total of 81,662 unrelated individuals across 70 countries and 40 unique ethnic groups. The results revealed that CYP2C9*2 was most abundant in Europe and the Middle East, whereas CYP2C9*3 was the main reason for reduced CYP2C9 activity across South Asia. Our data show extensive variation within superpopulations with up to tenfold differences between geographically adjacent populations in Malaysia, Thailand and Vietnam. Translation of genetic CYP2C9 variability into functional consequences indicates that up to 40% of patients in Southern Europe and the Middle East might benefit from warfarin and phenytoin dose reductions, while 3% of patients in Southern Europe and Israel are recommended to reduce starting doses of NSAIDs. Conclusions This study provides a comprehensive map of the genetic and functional variability of CYP2C9 with high ethnogeographic resolution. The presented data can serve as a useful resource for CYP2C9 allele and phenotype frequencies and might guide the optimization of genotyping strategies, particularly for indigenous and founder populations with distinct genetic profiles.

Insulin secretion is the process whereby insulin-containing granules fuse with the plasma membrane of β-cells. Exocytosis is preceded by cargo loading, maturation and transport of the secretory granules; processes that require modification of both the protein and lipid composition of the granules. We recently identified phosphatidylinositol-4 phosphate (PI[4]P) dephosphorylation by INPP5F/Sac2 on the surface of insulin granules as a key step that precedes stable granule docking at the plasma membrane and that is required for normal insulin secretion. Here, we show that PI(4)P is used to target the lipid exchange protein oxysterol-binding protein (OSBP) to the granule surface where it is involved in PI(4)P/cholesterol exchange. Loss of Sac2 resulted in excess accumulation of cholesterol on insulin granules that was normalized when OSBP expression was reduced. Acute inhibition of OSBP resulted in dramatic cellular redistribution of OSBP to insulin granules where it colocalized with the ER-resident protein VAP-A at ER-granule contact sites. Stimulation of insulin secretion also resulted in translocation of OSBP to the insulin granule surface in a process that depended on Ca2+-induced acidification of the cytosol. Similar to Sac2 knockdown, inhibition of OSBP suppressed insulin secretion without affecting insulin production. In conclusion, we show that lipid exchange at ER-granule contacts sites is involved in the exocytic process, and propose that these contacts act as reaction centers with multimodal functions during insulin granule maturation.

Type 2 diabetes (T2D) is caused by insufficient insulin secretion from pancreatic β cells. To identify candidate genes contributing to T2D pathophysiology, we studied human pancreatic islets from approximately 300 individuals. We found 395 differentially expressed genes (DEGs) in islets from individuals with T2D, including, to our knowledge, novel (OPRD1, PAX5, TET1) and previously identified (CHL1, GLRA1, IAPP) candidates. A third of the identified expression changes in islets may predispose to diabetes, as expression of these genes associated with HbA1c in individuals not previously diagnosed with T2D. Most DEGs were expressed in human β cells, based on single-cell RNA-Seq data. Additionally, DEGs displayed alterations in open chromatin and associated with T2D SNPs. Mouse KO strains demonstrated that the identified T2D-associated candidate genes regulate glucose homeostasis and body composition in vivo. Functional validation showed that mimicking T2D-associated changes for OPRD1, PAX5, and SLC2A2 impaired insulin secretion. Impairments in Pax5-overexpressing β cells were due to severe mitochondrial dysfunction. Finally, we discovered PAX5 as a potential transcriptional regulator of many T2D-associated DEGs in human islets. Overall, we have identified molecular alterations in human pancreatic islets that contribute to β cell dysfunction in T2D pathophysiology.

Geometrical shock dynamics (GSD) is a numerical model capable of efficiently predicting the position, shape and strength of a shock wave. Compared to the traditional Euler method that solves the inviscid Euler equations, GSD is a reduced-order model derived from the method of characteristics which results in a more computationally efficient approach since it only considers the motion of the shock front instead of the entire flow field. Here, a study of post-shock flow effects in two dimensions has been performed. These post-shock flow effects become increasingly important when modeling blast wave propagation over extended times or distances, i.e. a shock front that decays in speed and that has decaying properties behind it. A comparison between the first-order complete, and fully complete GSD models (point-source GSD and a model that combines PGSD and the shock-shock approximate theory for cylindrical shock reflection off a straight surface, called PGSDSS) reveals the importance of preserving an intact post-shock flow term, which is truncated by the original GSD model, in predicting blast motion. Lagrangian simulations were performed for the case of interaction between two cylindrical blast waves and results were compared to prior experimental work. Results showed an agreement in attenuation of the maximum pressure at the Mach stem, but an overestimation of the Mach stem growth at its early stage by PGSD was observed.