Policy Responses to Human Trafficking in Southern Africa: Domesticating International Norms

This is the author's accepted manuscript. The final published version will be available from Springer Verlag at http://dx.doi.org/10.1007/s12142-014-0303-9.Human trafficking is increasingly recognized as an outcome of economic insecurity, gender inequality, and conflict, all significant factors in the region of southern Africa. This paper examines policy responses to human trafficking in southern Africa and finds that there has been a diffusion of international norms to the regional and domestic levels. This paper finds that policy change is most notable in the strategies and approaches that differ at each level: international and regional agreements emphasize prevention measures and survivor assistance, but national policies emphasize prosecution measures. Leaders across the region have adapted these policy norms to fit regionally specific conditions, including HIV/AIDS, conflict, traditional leaders, and prostitution. Yet, national policies often fail to incorporate preventative solutions to address gender inequality, human rights, and economic development. Until appropriate funding and preventative measures are introduced, the underlying issues that foster human trafficking will continue

Qualitatively Different T Cell Phenotypic Responses to IL-2 versus IL-15 Are Unified by Identical Dependences on Receptor Signal Strength and Duration

IL-2 and IL-15 are common γ-chain family cytokines involved in regulation of T cell differentiation and homeostasis. Despite signaling through the same receptors, IL-2 and IL-15 have non-redundant roles in T cell biology, both physiologically and at the cellular level. The mechanisms by which IL-2 and IL-15 trigger distinct phenotypes in T cells remain elusive. To elucidate these mechanisms, we performed a quantitative comparison of the phosphotyrosine signaling network and resulting phenotypes triggered by IL-2 and IL-15. This study revealed that the signaling networks activated by IL-2 or IL-15 are highly similar and that T cell proliferation and metabolism are controlled in a quantitatively distinct manner through IL-2/15R signal strength independent of the cytokine identity. Distinct phenotypes associated with IL-2 or IL-15 stimulation therefore arise through differential regulation of IL-2/15R signal strength and duration because of differences in cytokine–receptor binding affinity, receptor expression levels, physiological cytokine levels, and cytokine–receptor intracellular trafficking kinetics. These results provide important insights into the function of other shared cytokine and growth factor receptors, quantitative regulation of cell proliferation and metabolism through signal transduction, and improved design of cytokine based clinical immunomodulatory therapies for cancer and infectious diseases.National Institutes of Health (U.S.) (Grant U54CA11927)National Institutes of Health (U.S.) (Grant R01 AI065824)United States. Army Research Office (Institute for Collaborative Biotechnologies Grant W911NF-09-0001

Six Months In: We Surge On

Steve Jobs created Apple in a garage. Facebook emerged out of a college dorm room. And so, like all good (and equally famous) things, the idea for Surge began in the Plank basement. As seniors, and admittedly all bonafide social justice enthusiasts, we wanted to expand the movement at Gettysburg College and leave our mark. [excerpt

Hot X-ray Onsets of Solar Flares

The study of the localized plasma conditions before the impulsive phase of a solar flare can help us understand the physical processes that occur leading up to the main flare energy release. Here, we present evidence of a hot X-ray onset interval of enhanced isothermal plasma temperatures in the range of 10-15~MK up to tens of seconds prior to the flare's impulsive phase. This `hot onset' interval occurs during the initial soft X-ray increase and prior to the detectable hard X-ray emission. The isothermal temperatures, estimated by the Geostationary Operational Environmental Satellite (GOES) X-ray sensor, and confirmed with data from the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI), show no signs of gradual increase, and the `hot onset' phenomenon occurs regardless of flare classification or configuration. In a small sample of four representative flare events we identify this early hot onset soft X-ray emission mainly within footpoint and low-lying loops, rather than with coronal structures, based on images from the Atmospheric Imaging Assembly (AIA). We confirm this via limb occultation of a flaring region. These hot X-ray onsets appear before there is evidence of collisional heating by non-thermal electrons, and hence they challenge the standard flare heating modeling techniques.Comment: Submitted to MNRAS 6 July 202

Hypertension

Defining hypertension in pregnancy is challenging because blood pressure levels in pregnancy are dynamic, having a circadian rhythm and also changing with advancing gestational age. The accepted definition is a sustained systolic (sBP) of ≥140 mmHg or a sustained diastolic blood pressure (dBP) ≥90 mmHg, by office (or in-hospital) measurement. Measurement of blood pressure in pregnancy should follow standardised methods, as outside pregnancy. Blood pressure measurement may occur in three types of settings, which will dictate in part, which measurement device(s) will be used. The settings are (1) health care facility; and two types of settings outside the facility: (2) ‘ambulatory’ blood pressure measurement (ABPM); and (3) home blood pressure measurement (HBPM). Furthermore, blood pressure can be measured using auscultatory (mercury or aneroid devices) or automated methods. Factors to consider when selecting a blood pressure measurement device include validation, disease specificity, observer error and the need for regular recalibration. The accuracy of a device is repeatedly compared to two calibrated mercury sphygmomanometers (the gold standard), by trained observers, over a range of blood pressures and for women with different hypertensive disorders of pregnancy; only a few devices have been validated among women with pre-eclampsia. This chapter discusses the advantages and/or disadvantages of the various settings and devices. Low- and middle-income countries (LMICs) bear a disproportionate burden of maternal morbidity and mortality from the hypertensive disorders of pregnancy. While regular blood pressure monitoring can cost-effectively reduce this disparity, LMIC-health systems face unique challenges that reduce this capacity. Assessment of service gaps and programmatic responses to ensure access to blood pressure measurement are a priority, supported where appropriate by implementation research.Publisher PD

Maternal Depressive Symptoms Predict General Liability in Child Psychopathology

Objective: The current study examines how maternal depressive symptoms relate to child psychopathology when structured via the latent bifactor model of psychopathology, a new organizational structure of psychopathological symptoms consisting of a general common psychopathology factor (p-factor) and internalizing- and externalizing-specific risk. Method: Maternal report of depressive symptoms (Beck Depression Inventory – II) and child psychopathological symptoms (Child Behavior Checklist and Children’s Behavior Questionnaire) were provided by 554 mother-child pairs. Children in the sample were 7.7 years old on average (SD = 1.35, range = 5–11 years), and were 49.8% female, 46% Latinx, and 67% White, 6% Black, 5% Asian/Pacific Islander, and 21% multiracial. Results: Maternal depressive symptoms were positively associated with the child p-factor but not with the internalizing- or externalizing-specific factors. We did not find evidence of sex/gender or race/ethnicity moderation when using latent factors of psychopathology. Consistent with past research, maternal depressive symptoms were positively associated with internalizing and externalizing composite scores on the Child Behavior Checklist. Conclusions: Findings suggest that maternal depressive symptoms are associated with transdiagnostic risk for broad child psychopathology (p-factor). Whereas the traditional Achenbach-style approach of psychopathological assessment suggests that maternal depressive symptoms are associated with both child internalizing and externalizing problems, the latent bifactor model suggests that these associations may be accounted for by risk pathways related to the p-factor rather than internalizing or externalizing specific risk. We discuss clinical and research implications of using a latent bifactor structure of psychopathology to understand how maternal depression may impact children’s mental health

Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)

Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis. Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B. Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype

Temperament Factors and Dimensional, Latent Bifactor Models of child psychopathology: Transdiagnostic and Specific Associations in Two Youth Samples

Common emotional and behavioral symptoms co-occur and are associated with core temperament factors. This study investigated links between temperament and dimensional, latent psychopathology factors, including a general common psychopathology factor (p factor) and specific latent internalizing and externalizing liabilities, as captured by a bifactor model, in two independent samples of youth. Specifically, we tested the hypothesis that temperament factors of negative affectivity (NA), positive affectivity (PA), and effortful control (EC) could serve as both transdiagnostic and specific risks in relation to recent bifactor models of child psychopathology. Sample 1 included 571 youth (average age 13.6, SD = 2.37, range 9.3–17.5) with both youth and parent report. Sample 2 included 554 preadolescent children (average age 7.7, SD = 1.35, range = 5–11 years) with parent report. Structural equation modeling showed that the latent bifactor models fit in both samples. Replicated in both samples, the p factor was associated with lower EC and higher NA (transdiagnostic risks). Several specific risks replicated in both samples after controlling for co-occurring symptoms via the p factor: internalizing was associated with higher NA and lower PA, lower EC related to externalizing problems

Lightweight transformers for clinical natural language processing

Specialised pre-trained language models are becoming more frequent in Natural language Processing (NLP) since they can potentially outperform models trained on generic texts. BioBERT (Sanh et al., Distilbert, a distilled version of bert: smaller, faster, cheaper and lighter. arXiv preprint arXiv: 1910.01108, 2019) and BioClinicalBERT (Alsentzer et al., Publicly available clinical bert embeddings. In Proceedings of the 2nd Clinical Natural Language Processing Workshop, pp. 72–78, 2019) are two examples of such models that have shown promise in medical NLP tasks. Many of these models are overparametrised and resource-intensive, but thanks to techniques like knowledge distillation, it is possible to create smaller versions that perform almost as well as their larger counterparts. In this work, we specifically focus on development of compact language models for processing clinical texts (i.e. progress notes, discharge summaries, etc). We developed a number of efficient lightweight clinical transformers using knowledge distillation and continual learning, with the number of parameters ranging from million to million. These models performed comparably to larger models such as BioBERT and ClinicalBioBERT and significantly outperformed other compact models trained on general or biomedical data. Our extensive evaluation was done across several standard datasets and covered a wide range of clinical text-mining tasks, including natural language inference, relation extraction, named entity recognition and sequence classification. To our knowledge, this is the first comprehensive study specifically focused on creating efficient and compact transformers for clinical NLP tasks. The models and code used in this study can be found on our Huggingface profile at https://huggingface.co/nlpie and Github page at https://github.com/nlpie-research/Lightweight-Clinical-Transformers, respectively, promoting reproducibility of our results

A systematic review of economic evaluations of interventions targeting childhood overweight and obesity

This systematic review critically appraised and synthesized evidence from economic evaluations of interventions targeting childhood excess weight. We conducted systematic searches in 11 databases from inception to April 19, 2023. Studies were eligible if they evaluated interventions targeting children up to 18 years and the study intervention(s) targeted childhood excess weight or sought to improve diet or physical activity, regardless of the type of economic evaluation or the underpinning study design. We synthesized evidence using narrative synthesis methods. One-hundred fifty-one studies met the eligibility criteria and were classified into three groups based on the intervention approach: prevention-only (13 studies), prevention and treatment (100 studies), and treatment-only (38 studies). The predominant setting and study design differed considerably between the three groups of studies. However, compared with usual care, most interventions were deemed cost-effective. The study participants' ages, sex, and socioeconomic status were crucial to intervention cost-effectiveness. Interventions whose effects were projected beyond childhood, such as bariatric surgery, lower protein infant formula, and home-based general practitioner consultations, tended to be cost-effective. However, cost-effectiveness was sensitive to the assumptions underlying the persistence and intensity of such effects. Our findings can inform future recommendations on the conduct of economic evaluations of interventions targeting childhood overweight and obesity, as well as practice and policy recommendations