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LIN28B-S in Huh7.5 cells

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LIN28B mRNA expression in human CRC samples

LIN28B short isoform in Huh7.5 cell

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This project concerns the development and subsequent distribution of a suite of computer codes that can accurately describe the interaction of charged particles (mostly electrons) and light (mostly lasers and synchrotrons) with atoms and ions. The results are of importance for the understanding of fundamental collision dynamics, and they also fulfil the urgent practical need for accurate atomic data to model the physics of stars, plasmas, lasers, and planetary atmospheres. With the rapid advances currently seen in computational resources, such studies can now be conducted for realistic systems. In particular, it has become possible to describe very complex targets, such as transition metals and other open-shell systems. The source code resulting from this project will be made publicly available. A website devoted to user-developer interaction will be developed and maintained together with the necessary code documentation and training materials.

Phylogenetic relationships among the four currently recognized species in the genus Erimyzon were reconstructed using sequence data obtained from the mitochondrially encoded COI and the nuclear-encoded IRBP2 genes. Maximum likelihood and Bayesian analyses yielded five groups of Erimyzon. Three of the clades corresponded to the species E. oblongus, E. tenuis, and E. claviformis. Individuals identified as E. sucetta were split into two separate clades, with one clade more closely related to E. oblongus than to the other E. sucetta clade in three of four analyses. Two instances of putative hybridization between sympatrically distributed species were also detected, one involving E. oblongus and E. sucetta and the other involving E. claviformis and E. tenuis. The results suggest that the currently recognized E. sucetta comprises two species, with potentially non-overlapping distributions. Further morphological investigation is warranted to provide additional support for recognizing this putative fifth species of Erimyzon.

Purpose Unintentional weight loss (UWL) is a prevalent problem in people with cancer and is associated with poorer psychosocial outcomes. A gap exists in understanding whether and how perceived and/or weight status impacts experiences of UWL. Thus, we sought to examine subjective experiences of UWL in people with cancer, and whether perceived and/or actual weight status impacts these experiences. Methods Participants were recruited through Cancer Support Community’s Cancer Experience Registry® and related networks. Participants completed an online survey that included the FAACT Anorexia-Cachexia subscale, and 19 items that captured six themes related to “beliefs and concerns” (positive beliefs, psychosocial impact, physical impact, cancer outcomes, self-esteem, relationships with others). Perceived weight status (PWS) was assessed using a single item. Body mass index (BMI) was calculated using self-reported weight and height measurements. Results Of 326 respondents, 114 reported experiencing UWL. Over one-third misperceived their weight, with 29% perceiving weight status as below their BMI status. UWL in those with perceived weight status of overweight/obese was associated with positive beliefs. However, being underweight by BMI or perceiving oneself as underweight were both associated with greater concerns about weight loss. Perceived weight status of underweight compared to normal or overweight/obese weight status was associated with poorer psychosocial well-being, personal control, self-esteem, and relationships with others. Conclusion In people with cancer, perceived weight status, rather than BMI, had greater impact on negative “beliefs and concerns” about UWL. Findings suggest assessment of both perceived and actual BMI to address the impact of UWL on psychosocial wellbeing.

1565 Background: Cancer is a cause of health inequalities, and nationally, patients from deprived communities have lower participation rates in cancer research. Equitable access to research benefits patients, healthcare organisations and improves applicability of research. Methods: We undertook a health equity audit of participation in cancer research (trials and non-trials based) in Bristol, North Somerset and South Gloucestershire (BNSSG), England from 1.4.2019-30.3.2020 using data from the Acute Trust patient datasets. Comparison cohorts were extracted from a regional primary care dataset (the system wide dataset). Firstly, an incident cancer cohort: diagnosed from 1.11.2019-1.10.2020. Secondly a “living with cancer” cohort: cancer flag in the 5 years prior to 1.7.2021. Deprivation is measured by IMD of home postcode small area (LSOA). Results: Results are presented for the audit in the table below, with 95% confidence intervals where appropriate. Compared to people newly diagnosed with cancer, adults aged 70 or older were 56% less likely to take part in research (OR 0.44, 95% CI 0.39-0.51), and adults aged 80 or older were 77% less likely to take part in research (OR 0.23, 95% CI 0.18-0.29). Compared to people newly diagnosed with cancer, people from the most deprived 20% of the population were 27% less likely to take part in research (OR 0.73, 95% CI 0.88-0.92). The most deprived research participants were more likely to be younger, have one or more comorbidities and a recent emergency admission. Patients from outside BNSSG (18%) appear similar in profile to those from within BNSSG, including for deprivation. Better data are needed for other factors relevant to equity, including ethnicity and Inclusion Health. Conclusions: This health equity audit confirms and quantifies inequities in access to cancer research in our region. Under-representation of deprived and older patients appeared multifactorial in this audit, but further work to understand facilitators and barriers to recruitment is needed. These results are a call to action. [Table: see text]

This protocol describes dissociation of a human intestinal biopsy tissue into single cells, followed by depletion of dead cells via annexin V MACS beads. The outcome is a single-cell suspension with viability ≥ 90% that is used for single-cell sequencing or establishemt of enteroid/colonoid culture.

Aims Self‐management programmes for type 1 diabetes, such as the UK’s Dose Adjustment for Normal Eating (DAFNE), improve short‐term clinical outcomes but difficulties maintaining behavioural changes attenuate long‐term impact. This study used the Behaviour Change Wheel (BCW) framework to revise the DAFNE intervention to support sustained behaviour change. Methods A four‐step method was based on the BCW intervention development approach: 1) Identifying self‐management behaviours and barriers/enablers to maintaining them via stakeholder consultation and evidence synthesis, and mapping barriers/enablers to the Capability, Opportunity, Motivation‐Behaviour (COM‐B) model. 2) Specifying behaviour change techniques (BCTs) in the existing DAFNE intervention using the Behaviour Change Techniques Taxonomy (BCTTv1). 3) Identifying additional BCTs to target the barriers/enablers using the BCW and BCTTv1. 4) Parallel stakeholder consultation to generate recommendations for intervention revision. Revised materials were co‐designed by stakeholders (diabetologists, psychologists, specialist nurses and dietitians). Results Thirty‐four barriers and five enablers to sustaining self‐management post‐DAFNE, were identified. The existing DAFNE intervention contained 24 BCTs, which partially addressed the enablers. Twenty‐seven BCTs were added, including ‘Habit formation’, ‘Credible source’ and ‘Conserving mental resources’. Fifteen stakeholder‐agreed recommendations for content and delivery were incorporated into the final DAFNEplus intervention, comprising three co‐designed components: (1) face‐to‐face group learning course, (2) individual structured follow‐up sessions, (3) technological support, including blood glucose data management. Conclusions This method provided a systematic approach to specifying and revising a behaviour change intervention incorporating stakeholder input. The revised DAFNEplus intervention aims to support the maintenance of behavioural changes by targeting barriers and enablers to sustaining self‐management behaviours.

This protocol describes dissociation of a human intestinal biopsy tissue into single cells, followed by depletion of dead cells via annexin V MACS beads. The outcome is a single-cell suspension with viability ≥ 90% that is used for single-cell sequencing or establishemt of enteroid/colonoid culture.

Aims\ud \ud Sustained engagement in type 1 diabetes self‐management behaviours is a critical element in achieving improvements in glycated haemoglobin (HbA1c) and minimising risk of complications. Evaluations of self‐management programmes, such as Dose Adjustment for Normal Eating (DAFNE), typically find that initial improvements are rarely sustained beyond 12 months. This study identified behaviours involved in sustained type 1 diabetes self‐management, their influences and relationships to each other.\ud \ud \ud Methods\ud \ud A mixed‐methods study was conducted following the first two steps of the Behaviour Change Wheel framework. First, an expert stakeholder consultation identified behaviours involved in self‐management of type 1 diabetes. Second, three evidence sources (systematic review, healthcare provider‐generated ‘red flags’ and participant‐generated ‘frequently asked questions’) were analysed to identify and synthesise modifiable barriers and enablers to sustained self‐management. These were characterised according to the Capability‐Opportunity‐Motivation‐Behaviour (COM‐B) model.\ud \ud \ud Results\ud \ud 150 distinct behaviours were identified and organised into three self‐regulatory behavioural cycles, reflecting different temporal and situational aspects of diabetes self‐management: Routine (e.g. checking blood glucose), Reactive (e.g. treating hypoglycaemia) and Reflective (e.g. reviewing blood glucose data to identify patterns). Thirty‐four barriers and five enablers were identified: 10 relating to Capability, 20 to Opportunity and nine to Motivation.\ud \ud \ud Conclusions\ud \ud Multiple behaviours within three self‐management cycles are involved in sustained type 1 diabetes self‐management. There are a wide range of barriers and enablers that should be addressed to support self‐management behaviours and improve clinical outcomes. The present study provides an evidence base for refining and developing type 1 diabetes self‐management programmes.

BackgroundPrimary care guidelines for managing adult overweight/obesity recommend routine measurement of body mass index (BMI) and the offer of weight management interventions. Many studies state that this is rarely done, but the extent to which overweight/obesity is recognised, considered, and documented in routine care has not been determined.AimTo identify the epidemiology of adult overweight documentation and management by UK GPs.Design and settingA systematic review of studies since 2006 from eight electronic databases and grey literature.MethodIncluded studies measured the proportion of adult patients with documented BMI or weight loss intervention offers in routine primary care in the UK. A narrative synthesis reports the prevalence and pattern of the outcomes.ResultsIn total, 2845 articles were identified, and seven were included; four with UK-wide data and three with regional-level data. The proportion of patients with a documented BMI was 58–79% (28–37% within a year). For overweight/obese patients alone, 43–52% had a recent BMI record, and 15–42% had a documented intervention offer. BMI documentation was positively associated with older age, female sex, higher BMI, coexistent chronic disease, and higher deprivation.ConclusionBMI is under-recorded and weight loss interventions are under-referred for primary care adult patients in the UK despite the obesity register in the Quality and Outcomes Framework (QOF). The review identified likely underserved groups such as younger males and otherwise healthy overweight/obese individuals to whom attention should now be directed. The proposed amendment to the obesity register QOF could prompt improvements but has not been adopted for 2017.

The choice between inclusion in a mainstream class or special needs setting is a difficult one for parents with a child with special needs. This chapter explores the complexities involved in making such a choice and acknowledges that there are many stakeholders involved in these decisions. I believe that it is important for parents to be fully informed about the choices that are available and the strengths and limitations of each setting. I also found that the social and emotional well-being of the child was paramount in the decisions that parents made. There are no right or wrong choices for parents, only the decision that feels right for the child and the family. For teachers choosing to work in special education settings empathy, passion and a desire to help others are necessary prerequisites.

Unintentional weight loss (UWL) is a prevalent problem in people with cancer and is associated with poorer psychosocial outcomes. A gap exists in understanding whether and how perceived and/or weight status impacts experiences of UWL. Thus, we sought to examine subjective experiences of UWL in people with cancer, and whether perceived and/or actual weight status impacts these experiences.Participants were recruited through Cancer Support Community's Cancer Experience Registry® and related networks. Participants completed an online survey that included the FAACT Anorexia-Cachexia subscale, and 19 items that captured six themes related to "beliefs and concerns" (positive beliefs, psychosocial impact, physical impact, cancer outcomes, self-esteem, relationships with others). Perceived weight status (PWS) was assessed using a single item. Body mass index (BMI) was calculated using self-reported weight and height measurements.Of 326 respondents, 114 reported experiencing UWL. Over one-third misperceived their weight, with 29% perceiving weight status as below their BMI status. UWL in those with perceived weight status of overweight/obese was associated with positive beliefs. However, being underweight by BMI or perceiving oneself as underweight were both associated with greater concerns about weight loss. Perceived weight status of underweight compared to normal or overweight/obese weight status was associated with poorer psychosocial well-being, personal control, self-esteem, and relationships with others.In people with cancer, perceived weight status, rather than BMI, had greater impact on negative "beliefs and concerns" about UWL. Findings suggest assessment of both perceived and actual BMI to address the impact of UWL on psychosocial wellbeing.

Background Identifying tuberculosis in homeless populations through active case finding (ACF) is recommended to address health inequalities and contribute to wider control strategies for tuberculosis. We aimed to assess the effectiveness of ACF. Methods This systematic review assessed studies on ACF done in countries with low or medium burden of tuberculosis across Europe, the USA, and Australia. We systematically searched EMBASE, CINAHL Plus, ASSIA, Pro-Quest, Scopus, and the Cochrane Library and grey literature for English language publications up to Jan 5, 2019 (no earlier date limit). We used concepts of “ACF”, “tuberculosis”, and “homeless person”. We identified studies that analysed ACF and reported on our outcome measures, in homeless populations, in low-burden and medium-burden countries. ACF screening included testing for latent tuberculosis infection (LTBI) or active tuberculosis affecting any site. Studies into outbreak control or other populations were excluded. Primary study outcomes were the effectiveness of ACF (using population measures of tuberculosis prevalence or incidence) and interventions to improve ACF uptake and completion of the diagnostic pathway. Secondary outcomes were yield of ACF, cost-effectiveness, and characteristics of participants. Findings 21 studies met the inclusion criteria. Study heterogeneity precluded meta-analysis. Three time-trend analyses produced some evidence that ACF was effective, because it was associated with reductions in tuberculosis incidence, prevalence, or clustering. A modelling study also showed that ACF was more effective than passive case finding in reducing population tuberculosis burden. Material incentives have the strongest evidence for improving uptake of ACF, with mixed evidence for peer educators. Observational evidence shows professional support and mandatory screening might also enhance uptake, and additional community-based support improves completion of the diagnostic pathway. Across all studies, the yield of screening (defined as the proportion of screened individuals who test positive) ranged from 1·5% to 57% for LTBI (total 41 684 individuals screened), and 0–3·1% for active tuberculosis (total 91 771 individuals screened). ACF can be cost-effective; population prevalence and screening modalities are determinants of cost-effectiveness. Considering ACF participants, subgroups most likely to be diagnosed with tuberculosis appeared less likely to accept screening. Interpretation ACF should be considered in both tuberculosis and homelessness strategies, with evidence-based interventions to improve implementation. Outcomes varied widely, meaning programmes must be tailored to local populations. Strengths of our study include generalisable results to homeless populations from diverse settings. Limitations include restriction to the English language, the fairly low grade of the evidence identified, and the low number of studies screening for LTBI or using newer screening tests. Funding The South West Public Health Training Programme.

Background:\ud Digital communication between a patient and their clinician offers the potential for improved patient care, particularly for young people with long term conditions who are at risk of service disengagement. However, its use raises a number of ethical questions which have not been explored in empirical studies. The objective of this study was to examine, from the patient and clinician perspective, the ethical implications of the use of digital clinical communication in the context of young people living with long-term conditions.\ud \ud Methods:\ud A total of 129 semi-structured interviews, 59 with young people and 70 with healthcare professionals, from 20 United Kingdom (UK)-based specialist clinics were conducted as part of the LYNC study. Transcripts from five sites (cancer, liver, renal, cystic fibrosis and mental health) were read by a core team to identify explicit and implicit ethical issues and develop descriptive ethical codes. Our subsequent thematic analysis was developed iteratively with reference to professional and ethical norms.\ud \ud Results:\ud Clinician participants saw digital clinical communication as potentially increasing patient empowerment and autonomy; improving trust between patient and healthcare professional; and reducing harm because of rapid access to clinical advice. However, they also described ethical challenges, including: difficulty with defining and maintaining boundaries of confidentiality; uncertainty regarding the level of consent required; and blurring of the limits of a clinician’s duty of care when unlimited access is possible. Paradoxically, the use of digital clinical communication can create dependence rather than promote autonomy in some patients. Patient participants varied in their understanding of, and concern about, confidentiality in the context of digital communication. An overarching theme emerging from the data was a shifting of the boundaries of the patient-clinician relationship and the professional duty of care in the context of use of clinical digital communication.\ud \ud Conclusions:\ud The ethical implications of clinical digital communication are complex and go beyond concerns about confidentiality and consent. Any development of this form of communication should consider its impact on the patient-clinician-relationship, and include appropriate safeguards to ensure that professional ethical obligations are adhered to.

BACKGROUND Digital consulting e.g. email, text and skype is increasingly offered to young people accessing specialist care for long term conditions. No patient reported outcome measures (PROM) have been evaluated for assessing outcomes of digital consulting. Systematic and scoping reviews, alongside patient involvement revealed two candidate PROMs for this purpose, the Patient Activation Measure (PAM) and the Physician’s Humanistic Behaviours Questionnaire (PHBQ). PAM measures knowledge, beliefs and skills that enable people to manage their long term condition. The PHBQ measures the extent to which behaviours that are important to patients in their physician-patient interactions are present. OBJECTIVE To explore i) whether the PAM and the PHBQ elicit important outcomes of digital consulting ii) whether the PROMs can isolate the digital consultation component of care. METHODS Participants were drawn from five clinics providing specialist NHS care to 16-24yrs olds with long term health conditions participating in the wider LYNC study. Fourteen people were convenience sampled and consented to have a cognitive interview in this sub-study. Seven participants were young people with either inflammatory bowel disease, cystic fibrosis or cancer. Seven clinicians were clinical psychologist, two nurses, three consultants and a community youth worker practising in Cancer, Diabetes, Cystic Fibrosis and Liver disease. Cognitive interviews were transcribed and analysed and a spread sheet recorded participants’ PROM item appraisals. Illustrative quotes were extracted verbatim from the interviews for all participants. RESULTS Young people found 10 of the PAM 13 items to be relevant to digital consulting and fewer of the additional PAM 22 items. They were only able to provide a spontaneous examples of digital consulting for 50% of the 22 items. Four of the 6 clinicians appraised 12 of the PAM 13 items and 19 of the PAM 22 items to be relevant to evaluating digital consulting and articulated operationalisation of the items with reference to their own digital consulting practice with greater ease than the young people. Appraising the PHBQ, in 14 of the 25 items (56%) 2/3rds of young people’s appraisals offered digital consulting examples with ease suggesting that the young people can detect and discern humanistic clinician behaviours via digital as well as face to face communication channels. Seventeen of the 25 items (68%) were appraised as relevant by the young people. This finding was mirrored in the clinician appraisals. Both young people and clinicians found the research task complex. Young participants required considerably more researcher prompting to illicit examples related to digital consulting rather than their face to face care. CONCLUSIONS The PAM and the PHBQ have satisfactory face and content validity for evaluating digital consulting to warrant proceeding to psychometric evaluation. Completion instructions require revision to differentiate between digital and face to face consultations.

BACKGROUND Since the introduction of digital health technologies in National Health Service (NHS), health professionals are starting to use email, text, and other digital methods to consult with their patients in a timely manner. There is lack of evidence regarding the economic impact of digital consulting in the United Kingdom (UK) NHS. OBJECTIVE This study aimed to estimate the direct costs associated with digital consulting as an adjunct to routine care at 18 clinics serving young people aged 16-24 years with long-term conditions. METHODS This study uses both quantitative and qualitative approaches. Semistructured interviews were conducted with 173 clinical team members on the impacts of digital consulting. A structured questionnaire was developed and used for 115 health professionals across 12 health conditions at 18 sites in the United Kingdom to collect data on time and other resources used for digital consulting. A follow-up semistructured interview was conducted with a single senior clinician at each site to clarify the mechanisms through which digital consulting use might lead to outcomes relevant to economic evaluation. We used the two-part model to see the association between the time spent on digital consulting and the job role of staff, type of clinic, and the average length of the working hours using digital consulting. RESULTS When estimated using the two-part model, consultants spent less time on digital consulting compared with nurses (95.48 minutes; P CONCLUSIONS Nurses and physiotherapists were the greatest users of digital consulting. Teams appear to use an efficient triage system with the most expensive members digitally consulting less than lower-paid team members. Staff report showed concerns regarding time spent digitally consulting, which implies that direct costs increase. There remain considerable gaps in evidence related to cost-effectiveness of digital consulting, but this study has highlighted important cost-related outcomes for assessment in future cost-effectiveness trials of digital consulting.

The RNA binding protein LIN28B plays an important role in development, stem cell biology and tumorigenesis. LIN28B has two isoforms: the LIN28B-long and -short isoforms. Although studies have revealed the functions of the LIN28B-long isoform in tumorigenesis, the role of the LIN28B-short isoform remains unclear and represents a major gap in the field. The LIN28B-long and -short isoforms are expressed in a subset of human colorectal cancers (CRCs) and adjacent normal colonic mucosa, respectively. To elucidate the functional and mechanistic aspects of these isoforms, CRC cells (Caco-2 and LoVo) were generated to either express no LIN28B or the -short or -long isoform. Interestingly, the long isoform suppressed LET-7 expression and activated canonical RAS/ERK signaling, while, the short isoform did not. The LIN28B-long isoform expressing cells demonstrated increased drug-resistance to 5-FU and cisplatin through the upregulation of ERCC1, a DNA repair gene, in a LET-7 dependent manner. The LIN28B-short isoform preserved its ability to bind pre-let-7, without inhibiting the maturation of LET-7, and competed with the LIN28B-long isoform for binding to pre-let-7. Co-expression of the short isoform in the LIN28B-long isoform expressing cells rescued the phenotypes induced by the LIN28B-long isoform.

BackgroundYoung people (aged 16–24 years) with long-term health conditions tend to disengage from health services, resulting in poor health outcomes. They are prolific users of digital communications. Innovative UK NHS clinicians use digital communication with these young people. The NHS plans to use digital communication with patients more widely.ObjectivesTo explore how health-care engagement can be improved using digital clinical communication (DCC); understand effects, impacts, costs and necessary safeguards; and provide critical analysis of its use, monitoring and evaluation.DesignObservational mixed-methods case studies; systematic scoping literature reviews; assessment of patient-reported outcome measures (PROMs); public and patient involvement; and consensus development through focus groups.SettingTwenty NHS specialist clinical teams from across England and Wales, providing care for 13 different long-term physical or mental health conditions.ParticipantsOne hundred and sixty-five young people aged 16–24 years living with a long-term health condition; 13 parents; 173 clinical team members; and 16 information governance specialists.InterventionsClinical teams and young people variously used mobile phone calls, text messages, e-mail and voice over internet protocol.Main outcome measuresEmpirical work – thematic and ethical analysis of qualitative data; annual direct costs; did not attend, accident and emergency attendance and hospital admission rates plus clinic-specific clinical outcomes. Scoping reviews–patient, health professional and service delivery outcomes and technical problems. PROMs: scale validity, relevance and credibility.Data sourcesObservation, interview, structured survey, routinely collected data, focus groups and peer-reviewed publications.ResultsDigital communication enables access for young people to the right clinician when it makes a difference for managing their health condition. This is valued as additional to traditional clinic appointments. This access challenges the nature and boundaries of therapeutic relationships, but can improve them, increase patient empowerment and enhance activation. Risks include increased dependence on clinicians, inadvertent disclosure of confidential information and communication failures, but clinicians and young people mitigate these risks. Workload increases and the main cost is staff time. Clinical teams had not evaluated the impact of their intervention and analysis of routinely collected data did not identify any impact. There are no currently used generic outcome measures, but the Patient Activation Measure and the Physicians’ Humanistic Behaviours Questionnaire are promising. Scoping reviews suggest DCC is acceptable to young people, but with no clear evidence of benefit except for mental health.LimitationsQualitative data were mostly from clinician enthusiasts. No interviews were achieved with young people who do not attend clinics. Clinicians struggled to estimate workload. Only eight full sets of routine data were available.ConclusionsTimely DCC is perceived as making a difference to health care and health outcomes for young people with long-term conditions, but this is not supported by evidence that measures health outcomes. Such communication is challenging and costly to provide, but valued by young people.Future workFuture development should distinguish digital communication replacing traditional clinic appointments and additional timely communication. Evaluation is needed that uses relevant generic outcomes.Study registrationTwo of the reviews in this study are registered as PROSPERO CRD42016035467 and CRD42016038792.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

e22131Background: Many cancer patients have concerns about nutrition, weight, fatigue, or fitness, but may have difficulty discussing these topics with their health care team (HCT). We examined ass...

The college campus is a complex system which necessitates the use of a variety of methods of intervention within an integrated model of consultation.

Further sources for those interested in pursuing the topic of campus consultation are provided in this chapter.

Counseling centers, and other student services agencies, can best serve their constituents by acknowledging and emphasizing the vast potential of preventive interventions.