Konfliktmineraler och internationellt ansvarstagande: En studie av Dodd-Frank Act 1502 och dess påverkan på stabiliteten i Demokratiska Republiken Kongo

Tävlan om kontroll över utvinning av eftertraktade mineraler i DR Kongo har lett till blodiga strider med förödande konsekvenser för civilbefolkningen. Landet är idag mycket fattigt och instabilt trots stora naturrikedomar. Mineralerna används i tillverkningen av en mängd elektronikprodukter som återfinns över hela världen och det är hög tid att det internationella samfundet tar sitt ansvar. Den amerikanska lagstiftningen Dodd-Frank Act 1502 är speciellt framtagen för att kontrollera handeln med så kallade konfliktmineraler och vår undersökning ämnar utreda hur lagen har påverkat stabiliteten i DR Kongo. Genom en komparativ studie över tid har vi nått resultatet att Dodd-Frank Act 1502 inte har haft någon större positiv inverkan på stabiliteten i DR Kongo. Med hjälp av konstruktivistisk normteori förklarar vi orsakerna till resultatets utfall och diskuterar lagens potential som en internationell norm med syfte att reglera handel med konfliktmineraler vilket ämnar skapa stabilitet i DR Kongo

Daily Step Count and Incident Diabetes in Community-Dwelling 70-Year-Olds: A Prospective Cohort Study

Background: Older adults with diabetes take fewer steps per day than those without diabetes. The purpose of the present study was to investigate the association of daily step count with incident diabetes in community-dwelling 70-year-olds. Methods: This prospective cohort study included N = 3055 community-dwelling 70-year-olds (52% women) who participated in a health examination in Umeå, Sweden during 2012–2017, and who were free from diabetes at baseline. Daily step count was measured for 1 week using Actigraph GT3X+ accelerometers. Cases of diabetes were collected from the Swedish National Patient Register. The dose-response association was evaluated graphically using a flexible parametric model, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox regressions. Results: During a mean follow-up of 2.6 years, diabetes was diagnosed in 81 participants. There was an inverse nonlinear dose-response association between daily step count and incident diabetes, with a steep decline in risk of diabetes from a higher daily step count until around 6000 steps/day. From there, the risk decreased at a slower rate until it leveled off at around 8000 steps/day. A threshold of 4500 steps/day was found to best distinguish participants with the lowest risk of diabetes, where those taking ≥ 4500 steps/day, had 59% lower risk of diabetes, compared to those taking fewer steps (HR, 0.41, 95% CI, 0.25–0.66). Adjusting for visceral adipose tissue (VAT) attenuated the association (HR, 0.64, 95% CI, 0.38–1.06), which was marginally altered after further adjusting for sedentary time, education and other cardiometabolic risk factors and diseases (HR, 0.58, 95% CI, 0.32–1.05). Conclusions: A higher daily step count is associated with lower risk of incident diabetes in community-dwelling 70-year-olds. The greatest benefits occur at the lower end of the activity range, and much earlier than 10,000 steps/day. With the limitation of being an observational study, these findings suggest that promoting even a modest increase in daily step count may help to reduce the risk of diabetes in older adults. Because VAT appears to partly mediate the association, lifestyle interventions targeting diabetes should apart from promoting physical activity also aim to prevent and reduce central obesity

The Desmoplastic Stroma Plays an Essential Role in the Accumulation and Modulation of Infiltrated Immune Cells in Pancreatic Adenocarcinoma

Tumor microenvironment is composed of tumor cells, fibroblasts, and infiltrating immune cells, which all work together and create an inflammatory environment favoring tumor progression. The present study aimed to investigate the role of the desmoplastic stroma in pancreatic ductal adenocarcinoma (PDAC) regarding expression of inflammatory factors and infiltration of immune cells and their impact on the clinical outcome. The PDAC tissues examined expressed significantly increased levels of immunomodulatory and chemotactic factors (IL-6, TGFβ, IDO, COX-2, CCL2, and CCL20) and immune cell-specific markers corresponding to macrophages, myeloid, and plasmacytoid dendritic cells (DCs) as compared to controls. Furthermore, short-time survivors had the lowest levels of DC markers. Immunostainings indicated that the different immune cells and inflammatory factors are mainly localized to the desmoplastic stroma. Therapies modulating the inflammatory tumor microenvironment to promote the attraction of DCs and differentiation of monocytes into functional DCs might improve the survival of PDAC patients

Modeling glioblastoma heterogeneity as a dynamic network of cell states

Tumor cell heterogeneity is a crucial characteristic of malignant brain tumors and underpins phenomena such as therapy resistance and tumor recurrence. Advances in single-cell analysis have enabled the delineation of distinct cellular states of brain tumor cells, but the time-dependent changes in such states remain poorly understood. Here, we construct quantitative models of the time-dependent transcriptional variation of patient-derived glioblastoma (GBM) cells. We build the models by sampling and profiling barcoded GBM cells and their progeny over the course of 3\ua0weeks and by fitting a mathematical model to estimate changes in GBM cell states and their growth rates. Our model suggests a hierarchical yet plastic organization of GBM, where the rates and patterns of cell state switching are partly patient-specific. Therapeutic interventions produce complex dynamic effects, including inhibition of specific states and altered differentiation. Our method provides a general strategy to uncover time-dependent changes in cancer cells and offers a way to evaluate and predict how therapy affects cell state composition

Higher-order symplectic Born-Oppenheimer molecular dynamics

The extended Lagrangian formulation of time-reversible Born-Oppenheimer molecular dynamics (TR-BOMD) enables the use of geometric integrators in the propagation of both the nuclear and the electronic degrees of freedom on the Born-Oppenheimer potential energy surface. Different symplectic integrators up to the 6th order have been adapted and optimized to TR-BOMD in the framework of ab initio self-consistent-field theory. It is shown how the accuracy can be significantly improved compared to a conventional Verlet integration at the same level of computational cost, in particular for the case of very high accuracy requirements

Low Birth Weight Is a Risk Factor for Severe Retinopathy of Prematurity Depending on Gestational Age

Objective: To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA). Study design In total, 2941 infants born <32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than −2.0 SDS using the Swedish reference and as BW below the 10th percentile using the Canadian reference charts. Results: Univariate analysis showed that low GA (p<0.001), low BW (p<0.001), male gender (p<0.05), low BWSDSCanada (p<0.001), and SGACanada (p<0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p<0.0001), male gender (p<0.01 and p<0.05), and an interaction term of BWSDS*GA group (p<0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA <26 weeks compared with infants born at GA ≥26 weeks calculated with both reference charts (BWSDSSweden, OR = 0.80 vs 0.56; and BWSDSCanada, OR = 0.72 vs 0.41). Conclusions: Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infant's degree of immaturity. In more mature infants (GA ≥26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches

Прикладна механіка і основи конструювання: навчально-методичний посібник

Розроблено відповідно до навчальної програми і призначено для виконання розрахунково-графічної роботи з дисципліни «Прикладна механіка і основи конструювання» студентам напряму підготовки 6.050202 «Автоматизація та компютерно-ігрегровані технології» денної та заочної форм навчання. Посібник рекомендовано також для самостійної роботи студентів, оскільки він вміщує короткі теоретичні викладки основного матеріалу дисципліни «Прикладна механіка і основи конструювання», умови завдань, приклади їх розв’язування, необхідні довідкові дані

Effects of dapagliflozin on symptoms, function and quality of life in patients with heart failure and reduced ejection fraction: results from the DAPA-HF trial

Background: Goals of management in patients with heart failure and reduced ejection fraction include reducing death and hospitalizations, and improving health status (symptoms, physical function, and quality of life). In the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure), sodium–glucose cotransporter-2 inhibitor, dapagliflozin, reduced death and hospitalizations, and improved symptoms in patients with heart failure and reduced ejection fraction. In this analysis, we examine the effects of dapagliflozin on a broad range of health status outcomes, using the Kansas City Cardiomyopathy Questionnaire (KCCQ). Methods: KCCQ was evaluated at randomization, 4 and 8 months. Patients were divided by baseline KCCQ total symptom score (TSS); Cox proportional hazards models examined the effects of dapagliflozin on clinical events across these subgroups. We also evaluated the effects of dapagliflozin on KCCQ-TSS, clinical summary score, and overall summary score. Responder analyses were performed to compare proportions of dapagliflozin versus placebo-treated patients with clinically meaningful changes in KCCQ at 8 months. Results: A total of 4443 patients had available KCCQ at baseline (median KCCQ-TSS, 77.1 [interquartile range, 58.3–91.7]). The effects of dapagliflozin vs placebo on reducing cardiovascular death or worsening heart failure were consistent across the range of KCCQ-TSS (lowest to highest tertile: hazard ratio, 0.70 [95% CI, 0.57–0.86]; hazard ratio, 0.77 [95% CI, 0.61–0.98]; hazard ratio, 0.62 [95% CI, 0.46–0.83]; P for heterogeneity=0.52). Patients treated with dapagliflozin had greater improvement in mean KCCQ-TSS, clinical summary score, and overall summary score at 8 months (2.8, 2.5 and 2.3 points higher versus placebo; P&lt;0.0001 for all). Fewer patients treated with dapagliflozin had a deterioration in KCCQ-TSS (odds ratio, 0.84 [95% CI, 0.78–0.90]; P&lt;0.0001); and more patients had at least small, moderate, and large improvements (odds ratio, 1.15 [95% CI, 1.08–1.23]; odds ratio, 1.15 [95% CI, 1.08–1.22]; odds ratio, 1.14 [95% CI, 1.07–1.22]; number needed to treat=14, 15, and 18, respectively; P&lt;0.0001 for all; results consistent for KCCQ clinical summary score and overall summary score). Conclusions: Dapagliflozin reduced cardiovascular death and worsening heart failure across the range of baseline KCCQ, and improved symptoms, physical function, and quality of life in patients with heart failure and reduced ejection fraction. Furthermore, dapagliflozin increased the proportion of patients experiencing at least small, moderate, and large improvements in health status; these effects were clinically important

Brain Abnormalities and Glioma-Like Lesions in Mice Overexpressing the Long Isoform of PDGF-A in Astrocytic Cells

BACKGROUND: Deregulation of platelet-derived growth factor (PDGF) signaling is a hallmark of malignant glioma. Two alternatively spliced PDGF-A mRNAs have been described, corresponding to a long (L) and a short (S) isoform of PDGF-A. In contrast to PDGF-A(S), the PDGF-A(L) isoform has a lysine and arginine rich carboxy-terminal extension that acts as an extracellular matrix retention motif. However, the exact role of PDGF-A(L) and how it functionally differs from the shorter isoform is not well understood.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS: We overexpressed PDGF-A(L) as a transgene under control of the glial fibrillary acidic protein (GFAP) promoter in the mouse brain. This directs expression of the transgene to astrocytic cells and GFAP expressing neural stem cells throughout the developing and adult central nervous system. Transgenic mice exhibited a phenotype with enlarged skull at approximately 6-16 weeks of age and they died between 1.5 months and 2 years of age. We detected an increased number of undifferentiated cells in all areas of transgene expression, such as in the subependymal zone around the lateral ventricle and in the cerebellar medulla. The cells stained positive for Pdgfr-α, Olig2 and NG2 but this population did only partially overlap with cells positive for Gfap and the transgene reporter. Interestingly, a few mice presented with overt neoplastic glioma-like lesions composed of both Olig2 and Gfap positive cell populations and with microvascular proliferation, in a wild-type p53 background.\ud \ud CONCLUSIONS: Our findings show that PDGF-A(L) can induce accumulation of immature cells in the mouse brain. The strong expression of NG2, Pdgfr-α and Olig2 in PDGF-A(L) brains suggests that a fraction of these cells are oligodendrocyte progenitors. In addition, accumulation of fluid in the subarachnoid space and skull enlargement indicate that an increased intracranial pressure contributed to the observed lethality.\ud \u

Replacing monocultures with mixed-species stands: Ecosystem service implications of two production forest alternatives in Sweden

Whereas there is evidence that mixed-species approaches to production forestry in general can provide positive outcomes relative to monocultures, it is less clear to what extent multiple benefits can be derived from specific mixed-species alternatives. To provide such insights requires evaluations of an encompassing suite of ecosystem services, biodiversity, and forest management considerations provided by specific mixtures and monocultures within a region. Here, we conduct such an assessment in Sweden by contrasting even-aged Norway spruce (Picea abies)-dominated stands, with mixed-species stands of spruce and birch (Betula pendula or B. pubescens), or spruce and Scots pine (Pinus sylvestris). By synthesizing the available evidence, we identify positive outcomes from mixtures including increased biodiversity, water quality, esthetic and recreational values, as well as reduced stand vulnerability to pest and pathogen damage. However, some uncertainties and risks were projected to increase, highlighting the importance of conducting comprehensive interdisciplinary evaluations when assessing the pros and cons of mixtures