Weight Loss and Illness Severity in Adolescents With Atypical Anorexia Nervosa.

BACKGROUND:Lower weight has historically been equated with more severe illness in anorexia nervosa (AN). Reliance on admission weight to guide clinical concern is challenged by the rise in patients with atypical anorexia nervosa (AAN) requiring hospitalization at normal weight. METHODS:We examined weight history and illness severity in 12- to 24-year-olds with AN (n = 66) and AAN (n = 50) in a randomized clinical trial, the Study of Refeeding to Optimize Inpatient Gains (www.clinicaltrials.gov; NCT02488109). Amount of weight loss was the difference between the highest historical percentage median BMI and admission; rate was the amount divided by duration (months). Unpaired t tests compared AAN and AN; multiple variable regressions examined associations between weight history variables and markers of illness severity at admission. Stepwise regression examined the explanatory value of weight and menstrual history on selected markers. RESULTS:Participants were 16.5 ± 2.6 years old, and 91% were of female sex. Groups did not differ by weight history or admission heart rate (HR). Eating Disorder Examination Questionnaire global scores were higher in AAN (mean 3.80 [SD 1.66] vs mean 3.00 [SD 1.66]; P = .02). Independent of admission weight, lower HR (β = -0.492 [confidence interval (CI) -0.883 to -0.100]; P = .01) was associated with faster loss; lower serum phosphorus was associated with a greater amount (β = -0.005 [CI -0.010 to 0.000]; P = .04) and longer duration (β = -0.011 [CI -0.017 to 0.005]; P = .001). Weight and menstrual history explained 28% of the variance in HR and 36% of the variance in serum phosphorus. CONCLUSIONS:Weight history was independently associated with markers of malnutrition in inpatients with restrictive eating disorders across a range of body weights and should be considered when assessing illness severity on hospital admission

A Cas9-based toolkit to program gene expression in Saccharomyces cerevisiae

Despite the extensive use of Saccharomyces cerevisiae as a platform for synthetic biology, strain engineering remains slow and laborious. Here, we employ CRISPR/Cas9 technology to build a cloning-free toolkit that addresses commonly encountered obstacles in metabolic engineering, including chromosomal integration locus and promoter selection, as well as protein localization and solubility. The toolkit includes 23 Cas9-sgRNA plasmids, 37 promoters of various strengths and temporal expression profiles, and 10 protein-localization, degradation and solubility tags. We facilitated the use of these parts via a web-based tool, that automates the generation of DNA fragments for integration. Our system builds upon existing gene editing methods in the thoroughness with which the parts are standardized and characterized, the types and number of parts available and the ease with which our methodology can be used to perform genetic edits in yeast. We demonstrated the applicability of this toolkit by optimizing the expression of a challenging but industrially important enzyme, taxadiene synthase (TXS). This approach enabled us to diagnose an issue with TXS solubility, the resolution of which yielded a 25-fold improvement in taxadiene production

Thinking like a man? The cultures of science

Culture includes science and science includes culture, but conflicts between the two traditions persist, often seen as clashes between interpretation and knowledge. One way of highlighting this false polarity has been to explore the gendered symbolism of science. Feminism has contributed to science studies and the critical interrogation of knowledge, aware that practical knowledge and scientific understanding have never been synonymous. Persisting notions of an underlying unity to scientific endeavour have often impeded rather than fostered the useful application of knowledge. This has been particularly evident in the recent rise of molecular biology, with its delusory dream of the total conquest of disease. It is equally prominent in evolutionary psychology, with its renewed attempts to depict the fundamental basis of sex differences. Wars over science have continued to intensify over the last decade, even as our knowledge of the political, economic and ideological significance of science funding and research has become ever more apparent

Developing a model of mental health self-care support for children and young people through an integrated evaluation of available types of provision involving systematic review, meta-analysis and case study

Background The mental health of children and young people (CYP) is a major UK public health concern. Recent policy reviews have identified that service provision for CYP with mental health needs is not as effective, responsive, accessible or child-centred as it could be. Following on from a previous National Institute for Health Research (NIHR) study into self-care support for CYP with long-term physical health needs, this study explored self-care support’s potential in CYP’s mental health. Objectives To identify and evaluate the types of mental health self-care support used by, and available to, CYP and their parents, and to establish how such support interfaces with statutory and non-statutory service provision. Design Two inter-related systematic literature reviews (an effectiveness review with meta-analysis and a perceptions review), together with a service mapping exercise and case study. Setting Global (systematic reviews); England and Wales (mapping exercise and case study). Participants (case study) Fifty-two individuals (17 CYP, 16 family members and 19 staff) were interviewed across six sites. Main outcome measures (meta-analysis) A measure of CYP’s mental health symptomatology. Data sources (literature reviews) MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, All Evidence-Based Medicine (EBM) Reviews, Applied Social Sciences Index and Abstracts (ASSIA) and Education Resources Information Center (ERIC). Review methods Titles and abstracts of papers were screened for relevance then grouped into studies. Two independent reviewers extracted data from studies meeting the inclusion criteria. A descriptive analysis and meta-analysis were conducted for the effectiveness review; descriptive analyses were conducted for the perceptions review. These analyses were integrated to elicit a mixed-methods review. Results Sixty-five of 71 included studies were meta-analysable. These 65 studies elicited 71 comparisons which, when meta-analysed, suggested that self-care support interventions were effective at 6-month [standardised mean difference (SMD) = −0.20; 95% confidence interval (CI) −0.28 to −0.11] and 12-month (SMD = −0.12; 95% CI −0.17 to −0.06) follow-ups. However, judged against Cochrane criteria, the studies were mostly low quality. Key elements of self-care support identified in the perceptions review were the acquisition of knowledge and skills, peer support and the relationship with the self-care support agent; CYP also had different perceptions from adults about what is important in self-care support. The mapping exercise identified 27 providers of 33 self-care support services. According to the case study data, effective self-care support services are predicated on flexibility; straightforward access; non-judgemental, welcoming organisations and staff; the provision of time and attention; opportunities to learn and practise skills relevant to self-care; and systems of peer support. Conclusions Mental health self-care support interventions for CYP are modestly effective in the short to medium term. Self-care support can be conceptualised as a process which has overlap with ‘recovery’. CYP and their families want choice and flexibility in the provision of such interventions and a continued relationship with services after the nominal therapy period. Those delivering self-care support need to have specific child-centred attributes. Future work Future work should focus on under-represented conditions (e.g. psychosis, eating disorders, self-harm); the role of technology, leadership and readiness in self-care support; satisfaction in self-care support; the conceptualisation of self-care support in CYP’s mental health; and efficacy and cost-effectiveness

Descartes, matemática e o mundo físico

Abstract The author's purpose in this article is to explore a different Descartes from the one presented by most commentators. In spite of the conventional wisdom, based mostly in Descartes' correspondence with Mersenne, the author presents a Descartes that is able to see, what Galileo and others saw, how mathematics can function in a physical theory

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Prevalence and Predictors of Loss of Wild Type BRCA1 in Estrogen Receptor Positive and Negative BRCA1-Associated Breast Cancers

Introduction: The majority of breast cancers that occur in BRCA1 mutation carriers (BRCA1 carriers) are estrogen receptor-negative (ER-). Therefore, it has been suggested that ER negativity is intrinsic to BRCA1 cancers and reflects the cell of origin of these tumors. However, approximately 20% of breast cancers that develop in BRCA1 carriers are ER-positive (ER+); these cancers are more likely to develop as BRCA1 carriers age, suggesting that they may be incidental and unrelated to BRCA1 deficiency. The purpose of this study was to compare the prevalence of loss of heterozygosity due to loss of wild type (wt) BRCA1 in ER+ and ER- breast cancers that have occurred in BRCA1 carriers and to determine whether age at diagnosis or any pathologic features or biomarkers predict for loss of wt BRCA1 in these breast cancers. Methods: Relative amounts of mutated and wt BRCA1 DNA were measured by quantitative polymerase chain reaction performed on laser capture microdissected cancer cells from 42 ER+ and 35 ER- invasive breast cancers that developed in BRCA1 carriers. BRCA1 gene methylation was determined on all cancers in which sufficient DNA was available. Immunostains for cytokeratins (CK) 5/6, 14, 8 and 18, epidermal growth factor receptor and p53 were performed on paraffin sections from tissue microarrays containing these cancers. Results: Loss of wt BRCA1 was equally frequent in ER+ and ER- BRCA1-associated cancers (81.0% vs 88.6%, respectively; P = 0.53). One of nine cancers tested that retained wt BRCA1 demonstrated BRCA1 gene methylation. Age at diagnosis was not significantly different between first invasive ER+ BRCA1 breast cancers with and without loss of wt BRCA1 (mean age 45.2 years vs 50.1 years, respectively; P = 0.51). ER+ BRCA1 cancers that retained wt BRCA1 were significantly more likely than those that lost wt BRCA1 to have a low mitotic rate (odds ratio (OR), 5.16; 95% CI, 1.91 to ∞). BRCA1 cancers with loss of wt BRCA1 were more likely to express basal cytokeratins CK 5/6 or 14 (OR 4.7; 95% CI, 1.85 to ∞). Conclusions: We found no difference in the prevalence of loss of wt BRCA1 between ER+ and ER- invasive BRCA1-associated breast cancers. Our findings suggest that many of the newer therapies for BRCA1 breast cancers designed to exploit the BRCA1 deficiency in these cancers may also be effective in ER+ cancers that develop in this population