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BACKGROUND There are limited qualitative data describing general pediatric hospitalizations through the caregivers’ lens, and most focus on one particular challenge or time during the hospitalization. This qualitative study aimed to address a gap in the description of the breadth and depth of personal challenges caregivers may face during the entire hospitalization, irrespective of severity of patient illness or diagnosis, and explored caregiver-suggested interventions. METHODS Caregivers of pediatric patients on the hospitalist service at a Pacific Northwest children’s hospital were interviewed to explore their hospitalization experience and solicit feedback for potential interventions. Content was coded iteratively using a framework analysis until thematic saturation was met. Findings were triangulated through 2 focus groups, 1 with parent advisors and the other with hospital physicians and nurses. RESULTS Among 14 caregivers (7 each of readmitted and newly admitted patients) and focus group participants, emergent domains on difficulties faced with their child’s hospitalization were anchored on physiologic (sleep, personal hygiene, and food), psychosocial (feelings of isolation, mental stress), and communication challenges (information flow between families and the medical teams). Caregivers recognized that addressing physiologic and psychosocial needs better enabled them to advocate for their child and suggested interventions to ameliorate hospital challenges. CONCLUSIONS Addressing physiologic and psychosocial needs may reduce barriers to caregivers optimally caring and advocating for their child. Downstream consequences of unaddressed caregiver challenges should be explored in relation to participation in hospital care and confidence in shared decision-making, both vital components for optimization of family-centered care.

Common genetic variants identified in genome-wide association studies (GWAS) show varying degrees of genetic pleiotropy across complex human disorders. Clinical studies of schizophrenia (SCZ) suggest that in addition to neuropsychiatric symptoms, patients with SCZ also show variable immune dysregulation. Epidemiological studies of multiple sclerosis (MS), an autoimmune, neurodegenerative disorder of the central nervous system, suggest that in addition to the manifestation of neuroinflammatory complications, patients with MS may also show co-occurring neuropsychiatric symptoms with disease progression. In this study, we analyzed the largest available GWAS datasets for SCZ (N = 161,405) and MS (N = 41,505) using Gaussian causal mixture modeling (MiXeR) and conditional/conjunctional false discovery rate (condFDR) frameworks to explore and quantify the shared genetic architecture of these two complex disorders at common variant level. Despite detecting only a negligible genetic correlation (r

Kadın üreticiler tarımsal üretimin her aşamasında yer almaktadır. Ancak tarımsal örgütlenme ve tarımsal pazarlama konularında yeteri kadar yer almamaktadırlar. Bu çalışma ile kadın çiftçilerin tarımsal örgütlenme konusundaki bilinçlerinin ve tarımsal kooperatiflerde yönetime katılma isteklerinin ortaya konulması amaçlanmıştır. Çalışmada Çanakkale ili Merkez ilçesinde en fazla tarım işletmesinin bulunduğu Kumkale köyü gayeli olarak seçilmiştir. Örnek hacminin belirlenmesinde oransal örnekleme yöntemi kullanılarak 80 kadın çiftçi ile anket yapılmıştır. Bu köydeki kadınlarla yapılan anket çalışması verileri Mann Whitney U testi ile analiz edilmiştir. İlave olarak verilerin analizinde temel tanımlayıcı istatistiklerden ve likert ölçekli sorulardan da yararlanılmıştır. Ortaya çıkan sonuçlarına göre kadın üreticiler kooperatif yönetimine katılım sağlamada isteklidirler. Kadın üreticiler başarılı kooperatifleri inceleyerek bu konudaki bilgilerini artırmak istemektedirler. Bu bağlamda yakın bölgedeki başarılı kooperatiflerde teknik incelemelerin yapılması ve bölgede kooperatifçilik eğitimlerinin verilmesi önerilmektedir.

The development of novel cancer therapies, including immuno-oncology agents, has increased interest in reconstructed individual patient data (IPD) based restricted mean survival time (RMST) analyses. Additionally, reconstructed IPD-based RMST is recommended in cost-effectiveness analyses when original trial IPD are not available. Nevertheless, recently concerns regarding potential bias of reconstructed-IPD RMST have been presented, because reconstructed-IPD RMSTs have not been validated and previous validation endpoints may not capture the entire Kaplan-Meier (KM) curve, especially the "tail." Our study aims to validate the recommended method of IPD reconstruction by comparing reconstructed IPD- and original trial IPD-based RMST.Canadian Cancer Trials Group trials from 1990 to 2017 were included. Overall survival and progression-free survival IPD were reconstructed based on published KM curves using the Guyot method. Analysts were blinded to original trial IPD. RMST was calculated at 1 year and over the entire KM curve. Reconstructed-IPD and original trial-IPD (gold-standard) RMSTs were compared for accuracy and predictive error via mean deviation, mean absolute error (MAE), mean percentage bias, and Bland-Altman plots and across KM curve quality (vector traced or bitmapped).We identified 39 trials. The mean deviation, MAE, and mean percentage bias of RMST between the reconstructed IPD and original trial IPD were small. In particular, the mean deviation was -0.01 months and -0.04 months, MAE was 0.19 months and 0.24 months, and mean percentage bias was 0.82% and 0.84% in overall survival KM curves in control and experimental arms, respectively. Accuracy was generally not associated with KM curve quality.RMST derived from reconstructed IPD displayed excellent accuracy and predictive error compared with the gold standard. Reconstructed IPD could be used to calculate RMST in lieu of original trial IPD, to facilitate decision making for clinicians, researchers, and policy makers.

Keats and Coleridge met for the one and only time on 11 April 1819. That accidental meeting embodied a range of circumstances and contexts which converged to create the conditions in which Keats’s poetic career advanced beyond its initial rapid development. Brief but intense exposure to Coleridge’s unceasingly philosophical turn of mind, as the two poets walked on Hampstead Heath, precipitated a newly self-conscious address on Keats’s part to the power of metaphor to express the mind’s activity in perception and artistic creation. This produced in the ‘Ode to Psyche’ a new level of intellectual sophistication, and a pathway to the achievement of the major Spring Odes which immediately followed.

In this study, we aimed to determine the genetic basis of a Turkish family related to hereditary spastic paraplegia (HSP) by exome sequencing. HSP is a progressive neurodegenerative disorder and displays genetic and clinical heterogeneity. The major symptoms are muscle weakness and spasticity, especially in the lower extremities. We studied seven affected and seven unaffected family members, as well as a clinically undetermined member, to identify the disease-causing gene. Exome sequencing was performed for four affected and two unaffected individuals. The variants were firstly filtered for HSP-associated genes, and we found a common variant in the ZFYVE27 gene, which has been previously implied for association with HSP. Due to the incompletely penetrant segregation pattern of the ZFYVE27 variant, revealed by Sanger sequencing, with the disease in this family, filtering was re-performed according to the mode of inheritance and allelic frequencies. The resulting 14 rare variants were further evaluated in terms of their cellular functions, and three candidate variants in ATAD3C, VPS16, and MYO1H genes were selected as possible causative variants, which were analyzed for their familial segregation. ATAD3C and VPS16 variants were eliminated due to incomplete penetrance. Eventually, the MYO1H variant NM_001101421.3:c.2972_2974del (p.Glu992del, rs372231088) was found as the possible disease-causing deletion for HSP in this family. This is the first study reporting the possible role of a MYO1H variant in HSP pathogenesis. Further studies on the cellular roles of Myo1h protein are needed to validate the causality of MYO1H gene at the onset of HSP.

This file contains: Supplementary material & methods Supplementary Figure S1 Globoside GSL synthesizing glycosyltransferases show elevated gene expression in epithelial tissue samples. Supplementary Figure S2 EMT marker gene expression in 47 ovarian cancer cell lines. Supplementary Figure S3 Single cell sorting strategy after transient transfection of sgRNA CRISPR-Cas9 constructs. Supplementary Figure S4 Quantification of glycans released from glycosphingolipids in wildtype and Î"A4GALT ovarian cancer cells using LC-ESI-MS/MS. Supplementary Figure S5 Dissemination of Î"A4GALT compared to IGROV1 wildtype cells. Supplementary Figure S6 The aspartate-any residue-aspartate motif is required for enzymatic activity of A4GALT. Supplementary Figure S7 Bicistronic expression of E-cadherinEGFP and A4GALT DXA shows enhanced extravasation in vivo. Supplementary Figure S8 Genetic depletion of A4GALT correlates with the absence of globosides in ovarian cancer cells representing the four different states of EMT. Supplementary Figure S9 Fluorescently labelled cells were transplanted into the Duct of Cuvier of 48 hpf zebrafish embryos and cells followed for 2-3 days. Supplementary Figure S10 Increased E-cadherin in SKOV3ip coincides with SLUG expression and histone modifications. Supplementary Table S1 Quantification of glycans released from glycosphingolipids in wildtype and Î"A4GALT ovarian cancer cells using LC-ESI-MS/MS. Supplementary Table S2 Cell lines used in this study. Supplementary Table S3 Table providing details of oligonucleotides used in this study. Supplementary references required for supplementary information

Even in the setting of optimal resuscitation in high-income countries severe sepsis and septic shock have a mortality of 20–40%, with antibiotic resistance dramatically increasing this mortality risk. To develop a reference dataset enabling the identification of common bacterial targets for therapeutic intervention, we applied a standardized genomic, transcriptomic, proteomic and metabolomic technological framework to multiple clinical isolates of four sepsis-causing pathogens: Escherichia coli, Klebsiella pneumoniae species complex, Staphylococcus aureus and Streptococcus pyogenes. Exposure to human serum generated a sepsis molecular signature containing global increases in fatty acid and lipid biosynthesis and metabolism, consistent with cell envelope remodelling and nutrient adaptation for osmoprotection. In addition, acquisition of cholesterol was identified across the bacterial species. This detailed reference dataset has been established as an open resource to support discovery and translational research.

Remarkable improvements in outcomes for many haematological malignancies have been driven primarily by a proliferation of novel therapeutics over the past two decades. Targeted agents, immune and cellular therapies, and combination regimens have adverse event profiles distinct from conventional finite cytotoxic chemotherapies. In 2018, a Commission comprising patient advocates, clinicians, clinical investigators, regulators, biostatisticians, and pharmacists representing a broad range of academic and clinical cancer expertise examined issues of adverse event evaluation in the context of both newer and existing therapies for haematological cancers. The Commission proposed immediate actions and long-term solutions in the current processes in adverse event assessment, patient-reported outcomes in haematological malignancies, toxicities in cellular therapies, long-term toxicity and survivorship in haematological malignancies, issues in regulatory approval from an international perspective, and toxicity reporting in haematological malignancies and the real-world setting. In this follow-up report, the Commission describes progress that has been made in these areas since the initial report.

OBJECTIVE Our aim was to understand the breadth of the hospital-to-home experience from the caregiver perspective using a mixed method approach. METHODS Caregivers of children who experienced an inpatient admission (N = 184) completed a hospital-to-home transition questionnaire after discharge. Twenty-six closed-ended survey items captured child’s hospitalization, discharge, and postdischarge experiences and were analyzed using descriptive statistics. Four additional free-response items allowed caregivers to expand on specific challenges or issues. A conventional content analysis coding framework was applied to the free responses. RESULTS Ninety-one percent of caregivers reported satisfaction with the hospital experience and 88% reported they understood how to manage their child’s health after discharge. A majority of survey respondents (74%) provided answers to 1 or more of the qualitative free-response items. In the predischarge period, qualitative responses centered on concerns related to finances or available resources and support, communication, hospital environment, and the discharge process. Responses for the postdischarge time period centered on family well-being (child health, other family member health), finances (bills, cost of missed work), and medical follow-up (supplies, appointments, instruction). CONCLUSIONS Caregivers were generally satisfied with their hospital experience; however, incorporating survey items specifically related to family stressors either through closed- or open-ended questions gave a richer context for caregiver-identified concerns. Basing future quality improvement efforts on supporting caregiver needs and identifying stressors before discharge may make for a more robust and successful transition to home.