Personality traits and musical interests of adult learners in an instrumental music program.

The survey yielded 127 respondents (N=127) from 18 states and one Canadian province. The survey categories included demographic information, life experiences, prior musical experiences, musical preferences, health issues, needed accommodations, and the IPIP-NEO personality profile.Participants were predominantly female, married, with an average age of 61.05. The majority resided in the Midwest area of the United States, was retired, and had earned an estimated gross annual income of $75,238.66. Most of the participants held bachelor's degrees.Respondents indicated their preferred rehearsal time was morning followed by evening. The greatest physical limitation indicated by subjects was arthritis/rheumatism closely followed by the need for large print music.Moderate trends were discovered between openness to experience and interest in listening to professionals, listening and playing styles preferences, performing preferences, the importance of lifelong learning, and willingness to participate in rehearsal activities. Moderate trends were discovered between extraversion and willingness to move to music as well as between agreeableness and willingness to sing.The purpose of this study was to assess the needs and musical interests of New Horizons Band members. A secondary purpose was to determine the relationship between personality traits and musical interests. An anonymous Music Interest Questionnaire was used along with the International Personality Item Pool representation of the NEO-PI-R(TM) (IPIP-NEO).The IPIP-NEO was used to investigate relationships between musical performing preferences, musical interests, importance of lifelong learning, and rehearsal activity preferences. Openness to experience, extraversion, and agreeableness were the only domains that revealed moderate trends between variables

Loss of Integrin-linked kinase sensitizes breast cancer to SRC inhibitors

SRC is a nonreceptor tyrosine kinase with key roles in breast cancer development and progression. Despite this, SRC tyrosine kinase inhibitors have so far failed to live up to their promise in clinical trials, with poor overall response rates. We aimed to identify possible synergistic gene–drug interactions to discover new rational combination therapies for SRC inhibitors. An unbiased genome-wide CRISPR-Cas9 knockout screen in a model of triple-negative breast cancer revealed that loss of integrin-linked kinase (ILK) and its binding partners α-Parvin and PINCH-1 sensitizes cells to bosutinib, a clinically approved SRC/ABL kinase inhibitor. Sensitivity to bosutinib did not correlate with ABL dependency; instead, bosutinib likely induces these effects by acting as a SRC tyrosine kinase inhibitor. Furthermore, in vitro and in vivo models showed that loss of ILK enhanced sensitivity to eCF506, a novel and highly selective inhibitor of SRC with a unique mode of action. Whole-genome RNA sequencing following bosutinib treatment in ILK knockout cells identified broad changes in the expression of genes regulating cell adhesion and cell–extracellular matrix. Increased sensitivity to SRC inhibition in ILK knockout cells was associated with defective adhesion, resulting in reduced cell number as well as increased G(1) arrest and apoptosis. These findings support the potential of ILK loss as an exploitable therapeutic vulnerability in breast cancer, enhancing the effectiveness of clinical SRC inhibitors. SIGNIFICANCE: A CRISPR-Cas9 screen reveals that loss of integrin-linked kinase synergizes with SRC inhibition, providing a new opportunity for enhancing the clinical effectiveness of SRC inhibitors in breast cancer

Syndromic Surveillance for Influenzalike Illness in Ambulatory Care Setting

Detection algorithm using proxy data for a bioterrorism agent release and historical data for influenza was effective

Cultural adaptation of a children's weight management programme for Bangladeshi and Pakistani families in the UK. A cluster-randomised feasibility study

AbstractBackground: Group-based children’s weight management programmes are widely available in the UK and evidence shows that these are effective in the short-term. No programmes have been specifically developed to meet the cultural requirements of UK minority ethnic communities. South Asian children are a high-risk group for obesity and its consequences; therefore, the study aim is to adapt an existing weight management programme for children aged 4-11 years and their families to ensure cultural relevance to Pakistani and Bangladeshicommunities, and undertake a feasibility study of the adapted programme.Methods/design: Pakistani and Bangladeshi families of overweight children who have been offered the existing children’s weight management programme in Birmingham, UK, will be invited to interviews and focus groups to explore their experiences and views of the programme. These data, together with existing literature and service provider information, will inform adaptation of the programme to be more culturally relevant to these families.The feasibility study will employ a cluster-randomised design, and will assess success of programme adaptation and feasibility of programme delivery. Planned programmes will be randomised to be delivered as the adapted programme (intervention) or the standard programme (comparator) with a 2:1 ratio. The primary outcome will be the proportion of Pakistani and Bangladeshi families completing the adapted programme. To assess recruitment, retention and data collection methods to inform a future trial, we aim to recruit 80 participants. A range of assessments will be undertaken with participants pre-, post- and 6-months post-intervention.Discussion: This study addresses the identified need to provide children’s weight management programmes that are suitable for minority ethnic communities. Whilst the focus of the intervention adaptation is on Pakistani and Bangladeshi communities, the programme will be developed to be flexibly delivered to meetthe cultural needs of communities of all ethnic compositions. The feasibility study will directly compare the adapted and existing weight management programmes, and will enable a comprehensive evaluation of the success of the adaptation. Essential information will also be gathered to inform the design and sample size calculation of a future trial to evaluate intervention effectiveness.Trial registration: ISRCTN81798055, registered: 13/05/2014.Keywords: Obesity, Children, Treatment, Weight management, Pakistani, Bangladesh

Haematopoietic SCT in severe autoimmune diseases: updated guidelines of the European Group for Blood and Marrow Transplantation

In 1997, the first consensus guidelines for haematopoietic SCT (HSCT) in autoimmune diseases (ADs) were published, while an international coordinated clinical programme was launched. These guidelines provided broad principles for the field over the following decade and were accompanied by comprehensive data collection in the European Group for Blood and Marrow Transplantation (EBMT) AD Registry. Subsequently, retrospective analyses and prospective phase I/II studies generated evidence to support the feasibility, safety and efficacy of HSCT in several types of severe, treatment-resistant ADs, which became the basis for larger-scale phase II and III studies. In parallel, there has also been an era of immense progress in biological therapy in ADs. The aim of this document is to provide revised and updated guidelines for both the current application and future development of HSCT in ADs in relation to the benefits, risks and health economic considerations of other modern treatments. Patient safety considerations are central to guidance on patient selection and HSCT procedural aspects within appropriately experienced and Joint Accreditation Committee of International Society for Cellular Therapy and EBMT accredited centres. A need for prospective interventional and non-interventional studies, where feasible, along with systematic data reporting, in accordance with EBMT policies and procedures, is emphasized

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

\ua9 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods: People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1\ub773 m2 or more to first eGFR of less than 30 mL/min per 1\ub773 m2 (the therapeutic trial window). Findings: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9\ub76 years (IQR 5\ub79–16\ub77). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2\ub781 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0\ub70001), but better survival rates (standardised mortality ratio 0\ub742 [95% CI 0\ub732–0\ub752]; p<0\ub70001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort

Background Individuals with rare kidney diseases account for 5–10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. Methods People aged 0–96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan–Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). Findings Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9–16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32–0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. Interpretation Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3–5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. Funding RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity