In the current study, data collected from Wave 6 of the Millennium Cohort Study (n = 11,872), a nationally representative sample survey of youth aged 14 years in the UK, are used to examine the ...prevalence of loneliness among this age-group, investigate the feelings associated with the experience of loneliness among youth, explore the risk factors for loneliness among young people, and learn how they coped with loneliness. Given recent findings that youth are vulnerable to loneliness, the study assesses the prevalence of loneliness among adolescents across some important sociodemographic characteristics, such as nation of residence, gender, and ethnicity. We also identify the kinds of social experiences that accompany loneliness during adolescence, exploring friendship, relations with parents, social support, and bullying. Our key finding is that, in addition to the absence of desired social relationships, which has been typically identified as the ultimate source of loneliness, the presence of undesirable and even harmful social relationships is a major source of loneliness. This study uniquely brings together psychological and sociological perspectives to understand the experience of youth loneliness.
This book traces the history of Argentine and Chilean pan-Americanism and asks why pan-Americanism came to define inter-American relations in the twentieth century.The Southern Cone and the Origins ...of Pan America, 1888-1933 offers new perspectives on the origins of the inter-American system and the history of international cooperation in the Americas. Mark J. Petersen chronicles the story of pan-Americanism, a form of regionalism launched by the United States in the 1880s and long associated with U.S. imperial pretensions in the Western hemisphere. The story begins and ends in the Rio de la Plata, with Southern Cone actors and Southern Cone agendas at the fore. Incorporating multiple strands of pan-American history, Petersen draws inspiration from interdisciplinary analysis of recent regionalisms and weaves together research from archives in Argentina, Chile, the United States, and Uruguay. The result is a nuanced and comprehensive account of how Southern Cone policy makers used pan-American cooperation as a vehicle for various agendas-personal, national, regional, hemispheric, and global-transforming pan-Americanism from a tool of U.S. interests to a framework for multilateral cooperation that persists to this day. Petersen decenters the story of pan-Americanism and orients the conversation on pan-Americanism toward a more complete understanding of hemispheric cooperation. The book will appeal to students and scholars of inter-American relations, Latin American (especially Chile and Argentina) and U.S. history, Latin American studies, and international relations.
PSMA PET is a promising method for primary lymph node staging in prostate cancer. However, recent systematic reviews have identified only a limited number of studies with histopathology as a ...reference test.
A systematic search was performed in PubMed and the Cochrane Library. An expedited systematic review was performed where we identified diagnostic studies in prostate cancer where a preoperative PSMA PET for primary lymph node staging was compared to histopathology. The trials must have diagnostic data on a patient level.
Eighteen eligible clinical trials included 969 patients. The median patient number per study was 32 (range 10 to 208). Five trials were prospective, and nine trials had a consecutive enrolment of patients. Sixteen studies used Ga-68-PSMA-11; there was one study with Cu-64-PSMA and one study with F-18-DCDFPyL. Twelve studies used PET/CT, four trials used PET/MR. Most trials included patients with intermediate and high-risk. Diagnostic accuracy varied notably among the studies; sensitivity ranged from 23 to 100%, specificity 67-100%, positive predictive value 20-100%, and negative predictive value 41-100%. Weighted sensitivity was 59%, weighted specificity was 93%. Four studies compared PSMA PET with anatomical imaging (CT or MRI); in all cases, sensitivity and specificity were superior with PSMA PET. Three studies compared PSMA PET with multi-parametric or diffusion-weighted MRI with mixed results.
PSMA PET showed promising diagnostic accuracy for primary lymph node staging with pathology as reference. Recommendation for PSMA PET for high-risk patients in clinical guidelines should be supported by confirmatory, prospective trials with patient-relevant outcomes.
Consumers frequently make important financial decisions that have short- and long-term impacts on their welfare. The authors expect that these financial decisions are a function of consumers' past ...experiences and interactions with a financial services firm as well as consumers' long-term priorities (e.g., national culture). They determine how three cultural dimensions (long-term orientation, uncertainty avoidance, and masculinity) and marketing communication type (promotion focused vs. prevention focused) affect three key consumer financial decisions: (1) savings rate, (2) use of credit, and (3) spending pattern. To do so, they empirically test both the direct effect of national culture on consumer financial decision making and its moderating effect on the link between a firm's marketing efforts and consumer financial decision making. Drawing on regulatory focus theory, the authors develop and empirically test their hypotheses using a customer database from a multinational financial services firm based in the United Arab Emirates, with customers originating from 34 countries. They find that national culture directly affects consumer financial decision making and moderates the impact of marketing efforts by the financial services firm, which suggests that financial services firms should account for national culture when managing customers.
This research uses data from a survey to explore the factors that affect organizations' manufacturing location decisions. Manufacturing location, more specifically the possibility of firms' ...nearshoring or reshoring, has received a great deal of recent attention, especially in the United States. This paper applies the location aspect of internalization theory to provide an understanding of what factors affect organizations' perceptions of the attractiveness of various regions as locations for owned manufacturing facilities. An exploratory factor analysis is used to develop factors that drive manufacturing location decisions. Multiple regression analysis is used to test the relationship between the drivers of manufacturing location decisions and movement of manufacturing into or out of a region, and overall perceived risk of a region. Findings indicate that various drivers have differential effects across regions. For example, while North America is viewed favorably for its trade policies over the next 3 years, the trade policies are also viewed as an increasing source of risk, possibly reflecting bipartisan conflicts. Three theoretical propositions are developed to advance the understanding of the current state of manufacturing location decisions from an internalization perspective. It appears that organizations are beginning to look at their manufacturing location decisions through a broader lens, giving more weight to supply chain issues as well as strategic factors.
Black Carbon (BC) may significantly affect nutrient retention and play a key role in a wide range of biogeochemical processes in soils, especially for nutrient cycling. Anthrosols from the Brazilian ...Amazon (ages between 600 and 8700 yr BP) with high contents of biomass‐derived BC had greater potential cation exchange capacity (CEC measured at pH 7) per unit organic C than adjacent soils with low BC contents. Synchrotron‐based near edge X‐ray absorption fine structure (NEXAFS) spectroscopy coupled with scanning transmission X‐ray microscopy (STXM) techniques explained the source of the higher surface charge of BC compared with non‐BC by mapping cross‐sectional areas of BC particles with diameters of 10 to 50 μm for C forms. The largest cross‐sectional areas consisted of highly aromatic or only slightly oxidized organic C most likely originating from the BC itself with a characteristic peak at 286.1 eV, which could not be found in humic substance extracts, bacteria or fungi. Oxidation significantly increased from the core of BC particles to their surfaces as shown by the ratio of carboxyl‐C/aromatic‐C. Spotted and non‐continuous distribution patterns of highly oxidized C functional groups with distinctly different chemical signatures on BC particle surfaces (peak shift at 286.1 eV to a higher energy of 286.7 eV) indicated that non‐BC may be adsorbed on the surfaces of BC particles creating highly oxidized surface. As a consequence of both oxidation of the BC particles themselves and adsorption of organic matter to BC surfaces, the charge density (potential CEC per unit surface area) was greater in BC‐rich Anthrosols than adjacent soils. Additionally, a high specific surface area was attributable to the presence of BC, which may contribute to the high CEC found in soils that are rich in BC.
Precise temporal control of gene expression or deletion is critical for elucidating gene function in biological systems. However, the establishment of human pluripotent stem cell (hPSC) lines with ...inducible gene knockout (iKO) remains challenging. We explored building iKO hPSC lines by combining CRISPR/Cas9-mediated genome editing with the Flp/FRT and Cre/LoxP system. We found that “dual-sgRNA targeting” is essential for biallelic knockin of FRT sequences to flank the exon. We further developed a strategy to simultaneously insert an activity-controllable recombinase-expressing cassette and remove the drug-resistance gene, thus speeding up the generation of iKO hPSC lines. This two-step strategy was used to establish human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC) lines with iKO of SOX2, PAX6, OTX2, and AGO2, genes that exhibit diverse structural layout and temporal expression patterns. The availability of iKO hPSC lines will substantially transform the way we examine gene function in human cells.
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•Efficient strategy outlined for engineering clonal inducible gene knockout hPSC lines•Dual-sgRNA targeting is essential for precise biallelic knockin of FRT•Inducible gene knockout can occur in all cells at any differentiation stages•Multiple genes can be targeted for inducible knockout
By combining CRISPR/Cas9-mediated genome editing with the Flp/FRT and Cre/LoxP system, Chen et al. developed an efficient two-step strategy to generate inducible gene knockout hPSC lines with predictable gene mutations upon tamoxifen treatment at any stages of differentiation. The iKO hPSC lines will enable the elucidation of gene functions throughout differentiation.
The temporal response of changes in renal sodium reabsorption during increased renal sympathetic nerve activity has not been investigated. Central hypovolemia by application of lower-body ...negative-pressure (LBNP) elicits baroreceptor mediated sympathetic reflexes to maintain arterial blood pressure. We hypothesized, that during 90 min LBNP, the renal sodium retention would increase rapidly, remain increased during intervention, and return to baseline immediately after end of intervention.
30 young, healthy, sodium loaded, non-obese males were exposed to -15 mmHg LBNP, -30 mmHg LBNP, -15 mmHg LBNP + renin blockade or time-control (0 mmHg LBNP) for 90 min. Urine was collected every 15 min during 90 min of intervention and 60 min of recovery to identify a possible relation between time of intervention and renal response.
All intervention groups exhibited a comparable reduction in distal sodium excretion at the end of the intervention (P = 0.46 between groups; -15 mmHg: -3.1 ± 0.9 %, -30 mmHg: -2.9 ± 0.6 %, -15 mmHg + aslikiren: -1.8 ± 0.6 %). -15 mmHg+Aliskiren resulted in a slower onset, but all groups exhibited a continued reduction in sodium excretion after 1 h of recovery despite return to baseline of renin, aldosterone, diuresis and cardiovascular parameters.
Sympathetic stimulation for 90 min via LBNP at -30 mmHg LBNP compared to -15 mmHg did not result in a greater response in fractional Na
excretion, suggesting that additional baroreceptor unloading did not cause further increases in renal sodium reabsorption. Changes in distal Na
excretion were linear with respect to time (dose) of intervention, but seem to exhibit a saturation-like effect at a level around 4 %. The lack of recovery after 1 h is also a new finding that warrants further investigation.
Hip strength assessment plays an important role in the clinical examination of the hip and groin region. The primary aim of this study was to examine the absolute test–retest measurement variation ...concerning standardized strength assessments of hip abduction (ABD), adduction (ADD), external rotation (ER), internal rotation (IR), flexion (FLEX) and extension (EXT) using a hand‐held dynamometer. Nine subjects (five males, four females), physically active for at least 2.5 h a week, were included. Twelve standardized isometric strength tests were performed twice with a 1‐week interval in between by the same examiner. The test order was randomized to avoid systematic bias. Measurement variation between sessions was 3–12%. When the maximum value of four measurements was used, test–retest measurement variation was below 10% in 11 of the 12 individual hip strength tests and below 5% in five of the 12 tests. No systematic differences were present. Standardized strength assessment procedures of hip ABD, ER, IR, FLEX, with test–retest measurement variation below 5%, hip ADD below 6% and hip EXT below 8%, make it possible to determine even small changes in hip strength at the individual level.
Adrenaline is a fundamental circulating hormone for bodily responses to internal and external stressors. Chromaffin cells of the adrenal medulla (AM) represent the main neuroendocrine adrenergic ...component and are believed to differentiate from neural crest cells. We demonstrate that large numbers of chromaffin cells arise from peripheral glial stem cells, termed Schwann cell precursors (SCPs). SCPs migrate along the visceral motor nerve to the vicinity of the forming adrenal gland, where they detach from the nerve and form postsynaptic neuroendocrine chromaffin cells. An intricate molecular logic drives two sequential phases of gene expression, one unique for a distinct transient cellular state and another for cell type specification. Subsequently, these programs down-regulate SCP-gene and up-regulate chromaffin cell-gene networks. The AM forms through limited cell expansion and requires the recruitment of numerous SCPs. Thus, peripheral nerves serve as a stem cell niche for neuroendocrine system development.
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