Utilisation of specialist epilepsy services and antiseizure medication adherence rates in a cohort of people with epilepsy (PWE) accessing emergency care.

BACKGROUND: An epilepsy-related attendance at A&E is associated an increased risk of subsequent death within 6 months. Although further work is required to provide a definitive explanation to account for these findings, in the interim it would seem reasonable that services are designed to ensure timely access and provide support at a time of greatest risk. We aim to determine the frequency of patients accessing specialist neurology services following an epilepsy-related admission/unscheduled care episode and consider ASM adherence at the point of attendance. METHODS: Patients were identified retrospectively via the NHS Greater Glasgow and Clyde live integrated epilepsy Dashboard following an unscheduled epilepsy-related admission or A&E attendance between 1st January 2022 and 30th June 2022. We calculated adherence to anti-seizure medication for a period of 6 months prior to admission and defined poor medication adherence as a medication possession ratio of less than 80 %. We evaluated the rate of any outpatient neurology clinic attendance in the subsequent 3, 6 and 12 months following an epilepsy-related unscheduled care episode. Additional clinical information was identified via the electronic patient records. RESULTS: Between 1st Jan 2022 and 30th June 2022, there were 266 emergency care seizure-related attendances. The mean age at attendance was 46 years (range: 16-91). Most of PWE were males (63 %) and 37 % were females. Epilepsy classification-29.3 % had GGE, 41.7% had focal epilepsy, and in 29 % of cases the epilepsy was unclassified. Of the admissions, 107/ 266 (40.2 %) generated follow-up within 6 months of attendance. Poor medication adherence was noted in 54/266 (20.3 %). 28.2 % of cases had input from on-call neurology service during admission/ED attendance, and of those 60 % had ASM adjusted. 18 % of attendances had a background diagnosis of learning disability. One-third of attendances of PWE had a history of mental health disorder 35 % (93/266). 25 % of ED attendances noted an active history of alcohol consumption misuse or/and recreational drug use. 14 (5.5 %) of PWE died during the period of interest (12 months following the last ED visit). In 6/14 (42.3 %) death was associated with poor medication adherence. CONCLUSION: This study demonstrates that a significant proportion of patients who experienced seizure-related admissions/ attendance did not access specialist neurology services in a timely manner. In addition, poor medication adherence remains a problem for a substantial number of people living with epilepsy. Early access to specialist services may go some way to improving care and reducing excessive mortality in PWE by allowing anti-seizure medication to be titrated and poor medication adherence to be addressed in those at greatest risk.

The impact of the COVID-19 pandemic on a cohort of adults with epilepsy.

OBJECTIVES: The aim of this study was to assess the direct and indirect impacts of the COVID-19 pandemic on adults with epilepsy in Glasgow. METHODS: We used routinely collected data for a previously identified cohort of patients with epilepsy to evaluate access to scheduled and unscheduled care with quarterly rates of inpatient admissions, outpatient attendance and accident & emergency attendance calculated. Anti-seizure medication prescribing and persistence, incidence of anxiety and depression and deaths for a cohort of patients with epilepsy was evaluated prior to the pandemic in comparison to during the pandemic, from 2015 to 2021. RESULTS: All-cause mortality and epilepsy related mortality showed a statistically significant reduction during the pandemic. Although overall rates of out-patient hospital attendance dropped during the early stages of the pandemic (and had not returned to pre-pandemic levels by the end of 2021) epilepsy-related services saw maintenance of patient contact as a result of a rapid adoption of telephone clinics. A significant decrease in overall mortality was observed in PWE during the pandemic compared to the pre-pandemic period. COVID-19 was the single commonest cause of death in PWE during the pandemic (61/453) and 160 patients (3.7%) had at least 1 admission to hospital for COVID-19. Anti-seizure medication (ASM) prescribing remained rates remained stable during the pandemic. During the pandemic an average of 38.8% of cohort patients were treated for depression and 16.3% for anxiety per quarter, 8.2% and 12.4% of whom had not been previously treated for these conditions respectively. CONCLUSION: We have shown that during a national lockdown, in the context of a pandemic, mortality in patients with epilepsy has reduced, while out-patient services were delivered remotely, primarily via the telephone. The reasons for this remain unclear but suggest that some of the excess mortality in people with epilepsy may be potentially avoidable by changes in lifestyle.

Specialist epilepsy service input following an epilepsy related unscheduled care episode.

BACKGROUND: Emergency and unplanned epilepsy-related attendances are associated with an increased risk of subsequent death within 6 months. Although further work is required to provide a definitive explanation to account for these findings, in the interim it would seem reasonable that services are designed to ensure timely access and provide support at a time of greatest risk. We aim to determine the frequency of patients with epilepsy (PWE) accessing specialist neurology services following an epilepsy-related admission/unscheduled care episode. METHODS: Patients were included in the cohort if they had at least 1 prescription for an anti-seizure medication and at least one epilepsy-related admission, emergency department attendance, or outpatient neurology clinic attendance between January 2011 and November 2021. We evaluated the rate of any outpatient neurology clinic attendance in the subsequent 6 months following an epilepsy related unscheduled care episode. RESULTS: Of the 6,449 PWE included in the cohort, 4,465 were included for analysis. At the end of the follow up period less than 40% were accessing specialist services within 6 months of an episode of admission/ unscheduled care episode. Around a third (31.1%) of deaths occurred within 6 months of an epilepsy-related admission, and in the majority of cases patients were not seen by an epilepsy specialist in the period between discharge and death. The frequency of mental health comorbidity in PWE accessing unscheduled care remains very high with almost 80% having a diagnosis of either depression or anxiety. CONCLUSION: A significant proportion of PWE are not accessing specialist services in a timely manner following an episode of unscheduled care. Such provision may potentially provide an opportunity to reduce epilepsy related mortality by altering antiseizure medication doses and considering reversible factors associated with poor outcomes in PWE, such as poor medication adherence.

Trust and service engagement among people who inject drugs after release from prison.

BACKGROUND: Compounding histories of injecting drug use and incarceration can marginalise people engaging with services, making it difficult for them to address their health and social welfare needs, particularly when they navigate community re-entry service supports. Drawing on Hall and colleagues' five components of trust, this paper seeks to understand how trust in service providers fosters (or inhibits) effective service engagement from the perspective of people who inject drugs during the prison post-release period. METHODS: Between September 2018 and May 2020, qualitative in-depth interviews were completed with 48 adults (33 men, 15 women) recruited from SuperMIX (a longitudinal cohort study of people with a history of injection drug use in Victoria, Australia). Data relating to service engagement were coded against the five components of trust: competence, fidelity, honesty, global trust, and confidence. RESULTS: Reflections of post-release service engagement frequently focused on interactions with community corrections (parole) officers. Depictions of trust were consistently portrayed within the context of negative experiences and deficits, whereby trusting provider relationships and interactions were rarely described. Most participants recounted a stark absence of fidelity (that is, "pursuing a [client's] best interests"), with some participants detailing circumstances in which their vulnerability was purposefully, almost strategically, exploited. These encounters nearly always had the consequence of impeding the participant's positive progression in the post-release integration period. CONCLUSION: There is an urgent need to prioritise the client in health and social service delivery in the post-release transition-to-community period and recognise the importance of trust in delivering effective services to people whose life histories make them highly vulnerable to marginalisation.

Media and technology usage and attitudes in emergency department patients.

Introduction: Digital health technologies are increasingly being used in emergency medicine, many of which utilize smartphones and computers. Patient willingness to use these modalities is an important factor in successful implementation. Therefore, this study aimed to assess emergency department (ED) patients' use of and attitudes towards technology. Methods: This was a pooled sub-analysis of ED patients (≥18 years old) that were enrolled in two studies evaluating the ED patient experience in response to novel technological interventions. Participants completed the Media and Technology Usage and Attitudes Scale (MTUAS) that assessed computer and smartphone ownership; frequency of use of phone calls, texting, email, and smartphones; and anxiety and dependence attitudes on these technologies. Results: One hundred and forty-four participants completed the survey. Mean age was 47.2 years (SD 17.94); 61.8% were female; and 61.1% were white. There was high usage of smartphones (93.1%) and computers (74.3%). Participants most frequently used phone calling and texting and least commonly used email. Participants had a positive attitude (mean 3.9/5, SD 0.68) towards the use of these technologies. Discussion: ED patients reported high ownership of smartphones and computers, had a positive attitude towards their use, and had varying frequency with which they used different technologies. Future studies can use this information to inform the development of digital health interventions that utilize technologies that patients find most acceptable.

The influence of demographics and comorbidity on persistence with anti-seizure medication.

PURPOSE: To examine the rate of persistence with anti-seizure medications (ASMs) in a cohort of patients with epilepsy, and to investigate the impact of a range of clinical and demographic factors on persistence METHODS: Patients receiving ASMs for epilepsy were identified from linked, routinely collected data within the NHS Greater Glasgow and Clyde health board area between January 2011 and August 2019. Persistence with individual ASMs at 365-days after initiation was assessed using a 90-day allowable gap between individual prescriptions. Univariate logistic regression was used to estimate the association between 1-year persistence with ASM and demographic characteristics, comorbidities, and medication characteristics. RESULTS: In total, 6,449 patients with epilepsy were identified - 1,631 were new users of ASMs at baseline and 4,818 had been prescribed at least one ASM prior to baseline. Persistence with individual ASMs ranged 11.8% to 78.6%. Persistence was significantly lower in younger patients and patients who had previously been non-persistent to ASMs. Persistence was higher amongst those with cardiac comorbidities, previous stroke, or higher overall comorbidity, as well as those prescribed newer ASMs. CONCLUSION: Persistence varied widely. Demographic factors, previous non-persistence and overall number of comorbidities were more important determinants of persistence to anti-seizure medications than specific individual comorbidities. Interventions to improve persistence should be targeted at younger patients from more deprived backgrounds and those who have previously been non-persistent with ASMs.

'Not just one box that you tick off' - Deconstructing the hepatitis C care cascade in the interferon-free direct acting antiviral era from the client perspective.

BACKGROUND: To achieve hepatitis C viral (HCV) elimination targets set by the World Health Organisation, pillars of the HCV care cascade are often referenced to track progress. The aim of this qualitative study was to explore the limitations of the care cascade framework through the real-world accounts of 'HCV journeys' among people who inject drugs (PWID), with particular attention to the intersection of PWID agency and structural determinants in the healthcare system. METHODS: An in-depth analysis was conducted on five case studies to better understand participant experiences 'behind the cascade pillars'. The five case studies were drawn from the ETHOS Engage cohort as exemplars of the real-world complexities of people's HCV cascade journeys. Inclusion criteria for the qualitative study were participant has voluntarily signed the informed consent form, aged ≥18 years, HCV antibody positive by self-report, clients of selected sites participating in the ETHOS Engage cohort, and sufficiently proficient in English to participate in an interview. Thirty-four semi-structured interviews were conducted with participants who had received or had not received HCV treatment to identify barriers and facilitators to HCV care. RESULTS: Participants 'housed' at the 'HCV RNA diagnosed pillar' (n = 2; Will; Julie) reported withholding their HCV serostatus in certain healthcare settings for fear that disclosure would lead to discriminatory decision-making from their treating physician. among participants who had completed treatment (n = 3; Corey; John; Nora) two reported still being unsure of their HCV status >6 months post-treatment. Ongoing feelings of frustration and shame were expressed in this 'post-cure care pillar' due to a perceived lack of quality care from clinic services and continued uneasiness when discussing drug use and reinfection while receiving opioid agonist treatment (OAT). Both case 'categories' described often tenuous therapeutic relationships with their physicians and recommended task-shifting to nurses and trusted case workers for ongoing care. CONCLUSION: The care cascade provides a linear, two dimensional snapshot of clinical targets. Our findings illuminate structural barriers not visible behind its 'static' pillars, presenting insights into experiences among PWID otherwise dismissed as 'disengaged' or 'lost to follow-up'.

Non-fatal opioid overdose, naloxone access, and naloxone training among people who recently used opioids or received opioid agonist treatment in Australia: The ETHOS Engage study.

BACKGROUND: Overdose is a major cause of morbidity and mortality among people who use opioids. Naloxone can reverse opioid overdoses and can be distributed and administered with minimal training. People with experience of overdose are a key population to target for overdose prevention strategies. This study aims to understand if factors associated with recent non-fatal opioid overdose are the same as factors associated with naloxone access and naloxone training in people who recently used opioids or received opioid agonist treatment (OAT). METHODS: ETHOS Engage is an observational study of people who inject drugs in Australia. Logistic regression models were used to estimate odds ratios for non-fatal opioid overdose, naloxone access and naloxone training. RESULTS: Between May 2018-September 2019, 1280 participants who recently used opioids or received OAT were enrolled (62% aged >40 years; 35% female, 80% receiving OAT, 62% injected drugs in the preceding month). Recent opioid overdose (preceding 12 months) was reported by 7% of participants, lifetime naloxone access by 17%, and lifetime naloxone training by 14%. Compared to people receiving OAT with no additional opioid use, recent opioid, benzodiazepine (preceding six months), and hazardous alcohol use was associated with recent opioid overdose (aOR 3.91; 95%CI: 1.68-9.10) and lifetime naloxone access (aOR 2.12; 95%CI 1.29-3.48). Among 91 people who reported recent overdose, 65% had never received take-home naloxone or naloxone training. CONCLUSIONS: Among people recently using opioids or receiving OAT, benzodiazepine and hazardous alcohol use is associated with non-fatal opioid overdose. Not all factors associated with non-fatal overdose correspond to factors associated with naloxone access. Naloxone access and training is low across all groups. Additional interventions are needed to scale up naloxone provision.

Barriers and facilitators to engaging in hepatitis C management and DAA therapy among general practitioners and drug and alcohol specialists-The practitioner experience.

BACKGROUND: Since the advent of interferon-free, direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection, prescriber restrictions have been removed worldwide, permitting HCV management outside of hospital-based clinics. To date, there is limited knowledge of the practitioner experience with DAA treatments, particularly among those new to HCV care. The aim of this qualitative study was to investigate barriers and facilitators for HCV management among general practitioners (GPs) who prescribe opioid agonist therapy (OAT) and drug and alcohol specialists. METHODS: In-depth, semi-structured telephone interviews were conducted between September 2018 and April 2019. Practitioners from across Australia were purposively sampled and questioned on barriers and facilitators to HCV management in their clinic(s). Data were coded and analysed with iterative categorisation and thematical analysis. RESULTS: Thirty practitioners were interviewed. Participants expressed professional fulfillment in managing HCV care and many benefited from specialist mentorship. Most participants expressed frustration with ongoing implementation barriers, notably, a lack of onsite phlebotomy services and liver disease staging equipment. Poor venous access among persons who inject drugs was elucidated as a major barrier to treatment initiation. Some participants did not receive clinic manager support to engage in HCV care. CONCLUSION: To achieve HCV targets set by WHO by 2030, practitioners require additional implementation support. As HCV testing remains a barrier to linkage to care, practitioners should be kept well-informed of diagnostic developments. Findings also underscore the importance of initial specialist mentorship with further evidence needed for practitioners based in rural regions.

ASCT2 regulates glutamine uptake and cell growth in endometrial carcinoma.

Glutamine commonly becomes a conditionally essential amino acid in cancer. Glutamine is supplied to the cell by transporters such as ASCT2 (SLC1A5), which is frequently upregulated in multiple cancers. Here we investigated the expression of ASCT2 in endometrial carcinoma, and evaluated the contribution of ASCT2 to glutamine uptake and endometrial cancer cell growth. Analysis of human gene expression data showed that ASCT2 was significantly upregulated in both endometrioid and serous subtypes of endometrial carcinoma, compared to normal, age-matched endometrium. Furthermore, immunohistochemical staining of primary human endometrioid adenocarcinomas showed that tumours stain positive for ASCT2 in either a uniform or mosaic expression pattern, while normal adjacent glands appeared predominantly negative for ASCT2 staining. Chemical inhibition of glutamine transport by benzylserine or GPNA led to a significant decrease in endometrial cancer cell growth and spheroid cross-sectional area. ASCT2 knockdown recapitulated the decrease of cell growth and spheroid cross-sectional area in HEC1A cells, suggesting a reliance on ASCT2-mediated glutamine uptake. ASCT2 knockdown in Ishikawa cells led to lower glutamine uptake and cell growth, but did not affect spheroid area. Ishikawa cells express higher levels of the glutamine transporter SNAT1 compared to HEC1A cells, suggesting these cells may rely on both ASCT2 and SNAT1 for glutamine uptake. Since SNAT1 is also significantly upregulated in the endometrioid and serous subtypes, these data indicate that ASCT2 and SNAT1 could be used as markers of malignancy, and/or potential therapeutic targets in patients with endometrial carcinoma.

CTCF genetic alterations in endometrial carcinoma are pro-tumorigenic.

CTCF is a haploinsufficient tumour suppressor gene with diverse normal functions in genome structure and gene regulation. However the mechanism by which CTCF haploinsufficiency contributes to cancer development is not well understood. CTCF is frequently mutated in endometrial cancer. Here we show that most CTCF mutations effectively result in CTCF haploinsufficiency through nonsense-mediated decay of mutant transcripts, or loss-of-function missense mutation. Conversely, we identified a recurrent CTCF mutation K365T, which alters a DNA binding residue, and acts as a gain-of-function mutation enhancing cell survival. CTCF genetic deletion occurs predominantly in poor prognosis serous subtype tumours, and this genetic deletion is associated with poor overall survival. In addition, we have shown that CTCF haploinsufficiency also occurs in poor prognosis endometrial clear cell carcinomas and has some association with endometrial cancer relapse and metastasis. Using shRNA targeting CTCF to recapitulate CTCF haploinsufficiency, we have identified a novel role for CTCF in the regulation of cellular polarity of endometrial glandular epithelium. Overall, we have identified two novel pro-tumorigenic roles (promoting cell survival and altering cell polarity) for genetic alterations of CTCF in endometrial cancer.

ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer.

Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake of glutamine and subsequent glutaminolysis is critical for activation of the mTORC1 nutrient-sensing pathway, which regulates cell growth and protein translation in cancer cells. This is of particular interest in breast cancer, as glutamine dependence is increased in high-risk breast cancer subtypes. Pharmacological inhibitors of ASCT2-mediated transport significantly reduced glutamine uptake in human breast cancer cell lines, leading to the suppression of mTORC1 signalling, cell growth and cell cycle progression. Notably, these effects were subtype-dependent, with ASCT2 transport critical only for triple-negative (TN) basal-like breast cancer cell growth compared with minimal effects in luminal breast cancer cells. Both stable and inducible shRNA-mediated ASCT2 knockdown confirmed that inhibiting ASCT2 function was sufficient to prevent cellular proliferation and induce rapid cell death in TN basal-like breast cancer cells, but not in luminal cells. Using a bioluminescent orthotopic xenograft mouse model, ASCT2 expression was then shown to be necessary for both successful engraftment and growth of HCC1806 TN breast cancer cells in vivo. Lower tumoral expression of ASCT2 conferred a significant survival advantage in xenografted mice. These responses remained intact in primary breast cancers, where gene expression analysis showed high expression of ASCT2 and glutamine metabolism-related genes, including GLUL and GLS, in a cohort of 90 TN breast cancer patients, as well as correlations with the transcriptional regulators, MYC and ATF4. This study provides preclinical evidence for the feasibility of novel therapies exploiting ASCT2 transporter activity in breast cancer, particularly in the high-risk basal-like subgroup of TN breast cancer where there is not only high expression of ASCT2, but also a marked reliance on its activity for sustained cellular proliferation.

Liver disease knowledge and acceptability of non-invasive liver fibrosis assessment among people who inject drugs in the drug and alcohol setting: The LiveRLife Study.

BACKGROUND: The aim of this study was to assess factors associated with baseline knowledge of HCV and liver disease, acceptability of transient elastography (TE) assessment (FibroScan(®)), and willingness and intent to receive HCV treatment among persons with a history of injection drug use participating in a liver health promotion campaign. METHODS: The LiveRLife campaign involved three phases: (1) campaign resource development; (2) campaign resource testing; and (3) campaign implementation. Participants were enrolled in an observational cohort study with recruitment at four clinics - one primary health care facility, two OST clinics, and one medically supervised injecting centre - in Australia between May and October 2014. Participants received educational material, nurse clinical assessment, TE assessment, dried blood spot testing, and completed a knowledge survey. RESULTS: Of 253 participants (mean age 43 years), 68% were male, 71% had injected in the past month, and 75% self-reported as HCV positive. Median knowledge score was 16/23. In adjusted analysis, less than daily injection (AOR 5.01; 95% CI, 2.64-9.51) and no daily injection in the past month (AOR 3.54; 95% CI, 1.80-6.94) were associated with high knowledge (≥16). TE was the most preferred method both pre- (66%) and post-TE (89%) compared to liver biopsy and blood sample. Eighty-eight percent were 'definitely willing' or 'somewhat willing' to receive HCV treatment, and 56% intended to start treatment in the next 12 months. Approximately 68% had no/mild fibrosis (F0/F1, ≥2.5 to ≤7.4kPa), 13% moderate fibrosis (F2, ≥7.5 to ≤9.4kPa), 10% severe fibrosis (F3, ≥9.5 to ≤12.4kPa), and 9% had cirrhosis (F4, ≥12.5kPa). CONCLUSION: Liver disease and HCV knowledge was moderate. High acceptability of TE by PWID provides strong evidence for the inclusion of TE in HCV-related care, and could help to prioritise HCV treatment for those at greatest risk of liver disease progression.

Survival from malignant mesothelioma: where are we now?

BACKGROUND: The prognosis of malignant pleural mesothelioma has traditionally been poor. Whether this remains the case compared to historical data and within a specific geographical location is uncertain. Knowledge of predictive factors for survival with malignant pleural mesothelioma is also inadequate. METHODS: We conducted a retrospective local database analysis to determine overall prognosis of patients with malignant pleural mesothelioma and evaluate the influence of demographic characteristics, histological subtype and laboratory parameters. Patients with histological diagnoses of malignant pleural mesothelioma held on the NHS Grampian pathology database between 2002 and 2012 were analysed. Data on baseline demographics, mode of diagnosis, histological sub-type, and survival and serum laboratory parameters, were analysed; time to death was examined using Cox regression analyses. RESULTS: A total of 114 patients with malignant pleural mesothelioma were included in the analysis. The median survival was 345 days (IQR 99-600). Sarcomatoid malignant pleural mesothelioma carried a significantly worse prognosis with median survival of 125 days (IQR 44-289) vs 334 days (IQR 126-715) for biphasic, 412 days (IQR 201-656) for epithelioid and 345 days (IQR 99-600) for those with no definitive typing. Individuals who did not receive chemotherapy experienced a significantly worse prognosis (hazard ratio 2.7; 95%CI 1.5-4.7; p = 0.001), while a low albumin and raised urea at time of diagnosis were also associated with a significantly poorer prognosis. CONCLUSION: The survival of patients with malignant pleural mesothelioma remains poor and typically around 1 year. The presence of raised urea and low albumin is associated with a poorer prognosis, while patients with a good performance status and few co-morbidities should be encouraged to receive chemotherapy.

Slowing down of adult body mass index trend increases in England: a latent class analysis of cross-sectional surveys (1992-2010).

BACKGROUND: The prevalence of excess body weight, commonly measured as body mass index (BMI)≥25 kg m(-2), has increased substantially in many populations worldwide over the past three decades, but the rate of increase has slowed down in some western populations. OBJECTIVE: We address the hypothesis that the slowing down of BMI trend increases in England reflects a majority sub-population resistant to further BMI elevation. DESIGN: Pseudo-panel data derived from annual cross-sectional surveys, the Health Surveys for England (1992-2010). Trends in median BMI values were explored using regression models with splines, and gender-specific mixture model (latent class analysis) were fit to take an account of increasing BMI distribution variance with time and identify hidden subgroups within the population. SUBJECTS: BMI was available for 164 155 adults (men: 76 382; women: 87 773). RESULTS: Until 2001, the age-adjusted yearly increases in median BMI were 0.140 and 0.139 kg m(-2) for men and women, respectively, decreasing thereafter to 0.073 and 0.055 kg m(-2) (differences between time periods, both P-values<0.0001). The mixture model identified two components--a normal BMI and a high BMI sub-population--the proportions for the latter were 23.5% in men and 33.7% in women. The remaining normal BMI populations were 'resistant' with minimal increases in mean BMI values over time. By age, mean BMI values in the normal BMI sub-population increased greatest between 20 and 34 years for men; for women, the increases were similar throughout age groups (slope differences, P<0.0001). CONCLUSION: In England, recent slowing down of adult BMI trend increases can be explained by two sub-populations--a high BMI sub-population getting 'fatter' and a majority 'resistant' normal BMI sub-population. These findings support a targeted, rather than a population-wide, policy to tackle the determinants of obesity.

Unusually high levels of n-6 polyunsaturated fatty acids in whale sharks and reef manta rays.

Fatty acid (FA) signature analysis has been increasingly used to assess dietary preferences and trophodynamics in marine animals. We investigated FA signatures of connective tissue of the whale shark Rhincodon typus and muscle tissue of the reef manta ray Manta alfredi. We found high levels of n-6 polyunsaturated fatty acids (PUFA), dominated by arachidonic acid (20:4n-6; 12-17 % of total FA), and comparatively lower levels of the essential n-3 PUFA-eicosapentaenoic acid (20:5n-3; ~1 %) and docosahexaenoic acid (22:6n-3; 3-10 %). Whale sharks and reef manta rays are regularly observed feeding on surface aggregations of coastal crustacean zooplankton during the day, which generally have FA profiles dominated by n-3 PUFA. The high levels of n-6 PUFA in both giant elasmobranchs raise new questions about the origin of their main food source.

Biology, ecology and conservation of the Mobulidae.

The Mobulidae are zooplanktivorous elasmobranchs comprising two recognized species of manta rays (Manta spp.) and nine recognized species of devil rays (Mobula spp.). They are found circumglobally in tropical, subtropical and temperate coastal waters. Although mobulids have been recorded for over 400 years, critical knowledge gaps still compromise the ability to assess the status of these species. On the basis of a review of 263 publications, a comparative synthesis of the biology and ecology of mobulids was conducted to examine their evolution, taxonomy, distribution, population trends, movements and aggregation, reproduction, growth and longevity, feeding, natural mortality and direct and indirect anthropogenic threats. There has been a marked increase in the number of published studies on mobulids since c. 1990, particularly for the genus Manta, although the genus Mobula remains poorly understood. Mobulid species have many common biological characteristics although their ecologies appear to be species-specific, and sometimes region-specific. Movement studies suggest that mobulids are highly mobile and have the potential to rapidly travel large distances. Fishing pressure is the major threat to many mobulid populations, with current levels of exploitation in target fisheries unlikely to be sustainable. Advances in the fields of population genetics, acoustic and satellite tracking, and stable-isotope and fatty-acid analyses will provide new insights into the biology and ecology of these species. Future research should focus on the uncertain taxonomy of mobulid species, the degree of overlap between their large-scale movement and human activities such as fisheries and pollution, and the need for management of inter-jurisdictional fisheries in developing nations to ensure their long-term sustainability. Closer collaboration among researchers worldwide is necessary to ensure standardized sampling and modelling methodologies to underpin global population estimates and status.