Identification of differentially distributed gene expression and distinct sets of cancer-related genes identified by changes in mean and variability.

There is increasing evidence that changes in the variability or overall distribution of gene expression are important both in normal biology and in diseases, particularly cancer. Genes whose expression differs in variability or distribution without a difference in mean are ignored by traditional differential expression-based analyses. Using a Bayesian hierarchical model that provides tests for both differential variability and differential distribution for bulk RNA-seq data, we report here an investigation into differential variability and distribution in cancer. Analysis of eight paired tumour-normal datasets from The Cancer Genome Atlas confirms that differential variability and distribution analyses are able to identify cancer-related genes. We further demonstrate that differential variability identifies cancer-related genes that are missed by differential expression analysis, and that differential expression and differential variability identify functionally distinct sets of potentially cancer-related genes. These results suggest that differential variability analysis may provide insights into genetic aspects of cancer that would not be revealed by differential expression, and that differential distribution analysis may allow for more comprehensive identification of cancer-related genes than analyses based on changes in mean or variability alone

Wandering behaviour prevents inter and intra oceanic speciation in a coastal pelagic fish

Small pelagic fishes have the ability to disperse over long distances and may present complex evolutionary histories. Here, Old World Anchovies (OWA) were used as a model system to understand genetic patterns and connectivity of fish between the Atlantic and Pacific basins. We surveyed 16 locations worldwide using mtDNA and 8 microsatellite loci for genetic parameters, and mtDNA (cyt b; 16S) and nuclear (RAG1; RAG2) regions for dating major lineage-splitting events within Engraulidae family. The OWA genetic divergences (0-0.4%) are compatible with intra-specific divergence, showing evidence of both ancient and contemporary admixture between the Pacific and Atlantic populations, enhanced by high asymmetrical migration from the Pacific to the Atlantic. The estimated divergence between Atlantic and Pacific anchovies (0.67 [0.53-0.80] Ma) matches a severe drop of sea temperature during the Gunz glacial stage of the Pleistocene. Our results support an alternative evolutionary scenario for the OWA, suggesting a coastal migration along south Asia, Middle East and eastern Africa continental platforms, followed by the colonization of the Atlantic via the Cape of the Good Hope.Portuguese Foundation for Science & Technology (FCT) [SFRH/BD/36600/2007]; FCT [UID/MAR/04292/2013, SFRH/BPD/65830/2009]; FCT strategic plan [UID/Multi/04326/2013]info:eu-repo/semantics/publishedVersio

Patient reported experiences and readmissions for people with diabetes-related foot disease admitted to public hospitals, New South Wales, Australia, 2019-2022.

OBJECTIVE: Patient reported measures of hospital care are known predictors of readmission, even after accounting for risk related to age and comorbidities. This study aimed to determine the association between patient experience of diabetes-related foot disease (DFD) hospital care and unplanned hospital readmission, with a primary focus on DFD-related readmissions and a secondary focus on all-cause readmissions. METHODS: A retrospective longitudinal cohort study was conducted by linking NSW Adult Admitted Patient Survey data with administrative hospital data for persons hospitalised with DFD identified through diagnostic and/or procedure codes. Univariable and multivariable shared-frailty Cox regression models were used to examine the association between key aspects of patient experiences and 90-days unplanned hospital readmission over the period 2019-2022. RESULTS: Overall, 3,173 DFD patients were included. Ninety-day readmission rates for respondents with DFD were 9% for DFD-related readmissions and 16% for all-cause readmissions. Adults with DFD who could not understand explanations offered by health professionals were at increased risk of DFD-related readmission compared to those who could always understand (Hazard ratio (HR) 2.43, CI: 1.47-4.00), as well as patients who did not feel well enough to leave hospital at discharge (HR 1.93, CI: 1.41-2.64) or reported the care received was not well organised (HR 2.24, 1.45-3.47). Patients reporting that they did not receive enough information regarding their condition, treatment, or how to manage care at home were found to have a DFD-related readmission risk that was 1.5 to 1.8-times greater than those who did. Similar patterns were observed for all-cause readmissions, albeit with generally smaller effect sizes. CONCLUSIONS: The findings highlight that elements of care related to communication, coordination, and involvement in decision making may influence unplanned readmission rates for patients with chronic conditions, such as DFD. The impact appears to be more pronounced for DFD-related readmissions compared to all-cause readmissions

Factors associated with adoption of organic paddy farming in Puttalam District in the context of organic food consumption trends

Amidst a significant uptick in organic product consumption driving the growth of organic agriculture, formulating policies to promote this method necessitates a thorough grasp of the factors influencing farmers' decisions to embrace organic cultivation. This study aims to investigate the determinants of farmers' choices to shift toward green agriculture. A sample of 150 rural paddy farmers was selected from Puttalam district using a multistage sampling technique, and data were collected through face-to-face interviews using a structured questionnaire. Seven key determinants have been discerned as critical contributors to this paradigm shift, such as Health Enhancement, Environmental Protection, Attitude, Economic Profitability, Knowledge of organic farming, Perceived Risk, and Government Support. In light of this, a conceptual model with seventeen hypotheses was created. Structural Equation Model (SEM) analysis was conducted using the Statistical Package for the Social Science (SPSS) and Analysis of Moment Structure (AMOS) to identify the direct, indirect, and mediating effects among the relevant variables. The estimated model revealed strong direct effects of economic profitability and perceived risk on organic farming adoption behavior, while government support had an indirect effect. Moreover, health enhancement demonstrated a significant direct effect on attitude, and knowledge emerged as a strong predictor with both significant direct and indirect effects on the dependent variable. The hypotheses concerning mediated pathways were also supported with partial and full mediators. These findings provide crucial insights for policymakers, guiding the development of appropriate policies and the implementation of sustainable organic farming practices among paddy farmers

Exploring consumer intention and perceptions towards purchasing local milk powder

Disputable information recently released through the mass media related to the imported milk powder has made a negative influence on powdered milk consumption in Sri Lanka. Conversely, this disputable information has been able to make high demand for local milk powder products. Therefore, this study was mainly focused to evaluate how the attitude towards the product, perceived knowledge, trust, price, availability, health consciousness, and subjective norms influence the local milk powder purchase intention of consumers. Primary data were collected through a questionnaire-based survey employing a face-to-face interview from a sample of 250 respondents covering five Divisional Secretariats in the Kegalle District. Data were analyzed by using Confirmatory Factor Analysis through Analysis of Moment Structure (AMOS). The results revealed that trust, health consciousness, availability and price are the main factors that influence the local milk powder purchase intention of the consumers. The results also show that the lack of availability is the major issue in the local milk powder industry. Hence, the findings of the case of Kegalle District, are important to policymakers, producers, vendors, and the government to implement better strategies for the development of the local milk powder industry in Sri Lanka

Developing a core outcome set for fistulising perianal Crohn's disease

OBJECTIVE: Lack of standardised outcomes hampers effective analysis and comparison of data when comparing treatments in fistulising perianal Crohn's disease (pCD). Development of a standardised set of outcomes would resolve these issues. This study provides the definitive core outcome set (COS) for fistulising pCD. DESIGN: Candidate outcomes were generated through a systematic review and patient interviews. Consensus was established via a three-round Delphi process using a 9-point Likert scale based on how important they felt it was in determining treatment success culminating in a final consensus meeting. Stakeholders were recruited nationally and grouped into three panels (surgeons and radiologists, gastroenterologists and IBD specialist nurses, and patients). Participants received feedback fromtheir panel(in the second round) andall participants(in the third round) to allow refinement of their scores. RESULTS: A total of 295 outcomes were identified from systematic reviews and interviews that were categorised into 92 domains. 187 stakeholders (response rate 78.5%) prioritised 49 outcomes through a three-round Delphi study.The final consensus meeting of 41 experts and patients generated agreement on an eight domain COS. The COS comprised three patient-reported outcome domains (quality of life, incontinence and a combined score of patient priorities) and five clinician-reported outcome domains (perianal disease activity, development of new perianal abscess/sepsis, new/recurrent fistula, unplanned surgery and faecal diversion). CONCLUSION: A fistulising pCD COS has been produced by all key stakeholders. Application of the COS will reduce heterogeneity in outcome reporting, thereby facilitating more meaningful comparisons between treatments, data synthesis and ultimately benefit patient care

Germline mutations and somatic inactivation of TRIM28 in Wilms tumour

© 2018 Halliday et al. http://creativecommons.org/licenses/by/4.0/ Wilms tumour is a childhood tumour that arises as a consequence of somatic and rare germline mutations, the characterisation of which has refined our understanding of nephrogenesis and carcinogenesis. Here we report that germline loss of function mutations in TRIM28 predispose children to Wilms tumour. Loss of function of this transcriptional co-repressor, which has a role in nephrogenesis, has not previously been associated with cancer. Inactivation of TRIM28, either germline or somatic, occurred through inactivating mutations, loss of heterozygosity or epigenetic silencing. TRIM28-mutated tumours had a monomorphic epithelial histology that is uncommon for Wilms tumour. Critically, these tumours were negative for TRIM28 immunohistochemical staining whereas the epithelial component in normal tissue and other Wilms tumours stained positively. These data, together with a characteristic gene expression profile, suggest that inactivation of TRIM28 provides the molecular basis for defining a previously described subtype of Wilms tumour, that has early age of onset and excellent prognosis

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Development of a core information set for colorectal cancer surgery: a consensus study

Objective ‘Core information sets’ (CISs) represent baseline information, agreed by patients and professionals, to stimulate individualised patient-centred discussions. This study developed a CIS for use before colorectal cancer (CRC) surgery. Design Three phase consensus study: (1) Systematic literature reviews and patient interviews to identify potential information of importance to patients, (2) UK national Delphi survey of patients and professionals to rate the importance of the information, (3) international consensus meeting to agree on the final CIS. Setting UK CRC centres. Participants Purposive sampling was conducted to ensure CRC centre representation based upon geographical region and caseload volume. Responses were received from 63/81 (78%) centres (90 professionals). Adult patients who had undergone CRC surgery were eligible, and purposive sampling was conducted to ensure representation based on age, sex and cancer location (rectum, left and right colon). Responses were received from 97/267 (35%) patients with a wide age range (29–87), equal sex ratio and cancer location. Attendees of the international Tripartite Colorectal Conference were eligible for the consensus meeting. Outcomes Phase 1: Information of potential importance to patients was extracted verbatim and operationalised into a Delphi questionnaire. Phase 2: Patients and professionals rated the importance information on a 9-point Likert scale, and resurveyed following group feedback. Information rated of low importance were discarded using predefined criteria. Phase 3: A modified nominal group technique was used to gain final consensus in separate consensus meetings with patients and professionals. Results Data sources identified 1216 pieces of information that informed a 98-item questionnaire. Analysis led to 50 and 23 information domains being retained after the first and second surveys, respectively. The final CIS included 11 concepts including specific surgical complications, short and long-term survival, disease recurrence, stoma and quality of life issues. Conclusions This study has established a CIS for professionals to discuss with patients before CRC surgery

Ambivalence related to potential lifestyle changes following preventive cardiovascular consultations in general practice: A qualitative study

<p>Abstract</p> <p>Background</p> <p>Motivational interviewing approaches are currently recommended in primary prevention and treatment of cardiovascular disease (CVD) in general practice in Denmark, based on an empirical and multidisciplinary body of scientific knowledge about the importance of motivation for successful lifestyle change among patients at risk of lifestyle related diseases. This study aimed to explore and describe motivational aspects related to potential lifestyle changes among patients at increased risk of CVD following preventive consultations in general practice.</p> <p>Methods</p> <p>Individual interviews with 12 patients at increased risk of CVD within 2 weeks after the consultation. Grounded theory was used in the analysis.</p> <p>Results</p> <p>Ambivalence related to potential lifestyle changes was the core motivational aspect in the interviews, even though the patients rarely verbalised this experience during the consultations. The patients experienced ambivalence in the form of conflicting feelings about lifestyle change. Analysis showed that these feelings interacted with their reflections in a concurrent process. Analysis generated a typology of five different ambivalence sub-types: perception, demand, information, priority and treatment ambivalence.</p> <p>Conclusion</p> <p>Ambivalence was a common experience in relation to motivation among patients at increased risk of CVD. Five different ambivalence sub-types were found, which clinicians may use to explore and resolve ambivalence in trying to aid patients to adopt lifestyle changes. Future research is needed to explore whether motivational interviewing and other cognitive approaches can be enhanced by exploring ambivalence in more depth, to ensure that lifestyle changes are made and sustained. Further studies with a wider range of patient characteristics are required to investigate the generalisability of the results.</p