Mental ill-health in mothers of people with intellectual disabilities compared with mothers of typically developing people: a systematic review and meta-analysis.

BACKGROUND: Mothers of people with intellectual disabilities (IDs) face exceptional challenges and may be more prone to experiencing mental ill-health compared with mothers of typically developing people. These mental ill-health problems may differ at different stages of the caregiving trajectory. However, there is no evidence synthesis on this topic. We aimed to systematically review evidence in this area and identify gaps in the existing literature. METHOD: Prospero registration: CRD42018088197. Medline, Embase, CINAHL and PsycINFO databases were searched. No time limits were applied. Studies were limited to English language. Inclusion criteria were studies of mothers of people with IDs that also included a comparison group of mothers of typically developing/developed children. Data were extracted from selected studies using a structured database. Study selection and quality appraisal were double rated. Where possible, meta-analyses were performed. RESULTS: Of the retrieved articles, 32/3089 were included, of which 10 reported on anxiety, 21 on depression and 23 on other indicators of mental ill-health. Overall, previous studies reported that mothers of people with IDs experienced poorer mental health as compared with mothers of typically developing people. Meta-analyses revealed significant findings for anxiety, depression, parenting stress, emotional burden and common mental disorders, but not for somatic symptoms. However, there was a considerable heterogeneity; hence, interpretation of results should be cautious. Identified gaps included scarce research on mental ill-health of mothers of adults with IDs at different stages of the caregiving trajectory. CONCLUSIONS: There is evidence of poorer mental ill-health in mothers of people with IDs compared with mothers of typically developing people, but lack of focus on different stages of the caregiving trajectory, methodological inconsistencies between studies and lack of robust studies pose limitations. This highlights the need both for improved support for mothers of people with IDs and for further methodologically robust research.

Antiretroviral Adherence, Drug Resistance, and the Impact of Social Determinants of Health in HIV-1 Patients in the US.

Adherence to antiretroviral therapy (ART) is critical to achieving viral suppression. However, social determinants of health (SDoH) can undermine patient adherence to ART, resulting in drug resistance that compromises future treatment options. We assessed ART adherence and HIV-1 drug resistance at the national and state levels in the US and investigated their associations with SDoH and other HIV-related outcomes. Data were obtained from Symphony Health's Integrated Dataverse (IDV), Monogram/LabCorp Database, as well as national and publicly available databases, including Centers for Disease Control and Prevention (CDC), American Community Survey (ACS), and J. Kaiser Family Foundation (KFF). Inferential analyses were performed to investigate associations using patient-level data, and the results were reported by state and overall within the nation. Correlations between continuous variables were estimated by the Spearman's test, and that between continuous variable and categorical variable were estimated using one-way analysis of variance (ANOVA). State-level rates of poor adherence and resistance ranged from 26 to 55% and 20 to 54%, respectively. Female gender, non-white race, low education, poverty, and unemployment were associated with poor adherence; female gender was associated with drug resistance. Both adherence and resistance were correlated to HIV prevalence rates. Our findings suggest that US patients living with HIV face great challenges associated with poor ART adherence and HIV-1 drug resistance.

Musculoskeletal consultations from childhood to adulthood: a longitudinal study.

BACKGROUND: The Global Burden of Disease reports indicate that musculoskeletal conditions are important causes of disability worldwide. Such conditions may originate in childhood, but studies investigating changes longitudinally and from childhood to adulthood are infrequent. METHODS: Nine birth cohorts of children (starting at ages 7-15 years) were followed. Participants were identified from Consultations in Primary Care Archive, an electronic health record database of 11 English general practices. Musculoskeletal consultation prevalence figures were calculated, and reasons for consultation evaluated. RESULTS: Annual musculoskeletal consultation prevalence was similar across cohorts for each age. Prevalence increased from 6 to 16% between ages 7 and 22 and was higher in males until age 15, after which prevalence was higher in females. Pain was the most common reason for consultation. Back pain consultations increased from 1 consultation/1000 7 year olds to 84 consultations/1000 22 year olds. Lower limb pain consultations increased from 21 consultations/1000 7 year olds to 56 consultations/1000 22 year olds. CONCLUSIONS: This study shows that from childhood, individuals are more likely to seek healthcare for musculoskeletal consultations as they age, but rates are not increasing over time. Changes in consultation rates by age, gender and pain region may inform studies on the development of chronic musculoskeletal pain over the life-course.

Stratified primary care versus non-stratified care for musculoskeletal pain: findings from the STarT MSK feasibility and pilot cluster randomized controlled trial.

BACKGROUND: Musculoskeletal (MSK) pain from the five most common presentations to primary care (back, neck, shoulder, knee or multi-site pain), where the majority of patients are managed, is a costly global health challenge. At present, first-line decision-making is based on clinical reasoning and stratified models of care have only been tested in patients with low back pain. We therefore, examined the feasibility of; a) a future definitive cluster randomised controlled trial (RCT), and b) General Practitioners (GPs) providing stratified care at the point-of-consultation for these five most common MSK pain presentations. METHODS: The design was a pragmatic pilot, two parallel-arm (stratified versus non-stratified care), cluster RCT and the setting was 8 UK GP practices (4 intervention, 4 control) with randomisation (stratified by practice size) and blinding of trial statistician and outcome data-collectors. Participants were adult consulters with MSK pain without indicators of serious pathologies, urgent medical needs, or vulnerabilities. Potential participant records were tagged and individuals sent postal invitations using a GP point-of-consultation electronic medical record (EMR) template. The intervention was supported by the EMR template housing the Keele STarT MSK Tool (to stratify into low, medium and high-risk prognostic subgroups of persistent pain and disability) and recommended matched treatment options. Feasibility outcomes included exploration of recruitment and follow-up rates, selection bias, and GP intervention fidelity. To capture recommended outcomes including pain and function, participants completed an initial questionnaire, brief monthly questionnaire (postal or SMS), and 6-month follow-up questionnaire. An anonymised EMR audit described GP decision-making. RESULTS: GPs screened 3063 patients (intervention = 1591, control = 1472), completed the EMR template with 1237 eligible patients (intervention = 513, control = 724) and 524 participants (42%) consented to data collection (intervention = 231, control = 293). Recruitment took 28 weeks (target 12 weeks) with > 90% follow-up retention (target > 75%). We detected no selection bias of concern and no harms identified. GP stratification tool fidelity failed to achieve a-priori success criteria, whilst fidelity to the matched treatments achieved "complete success". CONCLUSIONS: A future definitive cluster RCT of stratified care for MSK pain is feasible and is underway, following key amendments including a clinician-completed version of the stratification tool and refinements to recommended matched treatments. TRIAL REGISTRATION: Name of the registry: ISRCTN. TRIAL REGISTRATION NUMBER: 15366334. Date of registration: 06/04/2016.

Back pain, mental health and substance use are associated in adolescents.

BACKGROUND: During adolescence, prevalence of pain and health risk factors such as smoking, alcohol use and poor mental health all rise sharply. The aim of this study was to describe the relationship between back pain and health risk factors in adolescents. METHODS: Cross-sectional data from the Healthy Schools Healthy Futures study, and the Australian Child Wellbeing Project was used, mean age: 14-15 years. Children were stratified according to back pain frequency. Within each strata, the proportion of children that reported drinking alcohol or smoking or that experienced feelings of anxiety or depression was reported. Test-for-trend analyses assessed whether increasing frequency of pain was associated with health risk factors. RESULTS: Data was collected from ~2500 and 3900 children. Larger proportions of children smoked or drank alcohol within each strata of increasing pain frequency. The trend with anxiety and depression was less clear, although there was a marked difference between the children that reported no pain, and pain more frequently. CONCLUSION: Two large, independent samples show adolescents that experience back pain more frequently are also more likely to smoke, drink alcohol and report feelings of anxiety and depression. Pain appears to be part of the picture of general health risk in adolescents.

The prevalence and general health status of people with intellectual disabilities and autism co-occurring together: a total population study.

BACKGROUND: Little is known about the population prevalence of co-occurring intellectual disabilities and autism, and its impact on general health status. The study aimed to investigate this, in comparison with the general population. METHOD: Whole country data from Scotland's Census, 2011, were analysed. Descriptive statistics were generated; chi-squared tests were undertaken; and logistic regressions were undertaken both with the whole general population data, adjusted for age and gender, and within the population with co-occurring intellectual disabilities and autism. RESULTS: A total of 5709/5 295 403 (1.08/1000) people had co-occurring intellectual disabilities and autism; 2.58/1000 children/young people and 0.74/1000 adults. The peak reported prevalence was at age 10 years (3.78/1000); 66.0% were male. Their general health status was substantially poorer than for the rest of the population, more so for children/young people, and they had more limitations in their day-to-day activities. Co-occurring intellectual disabilities and autism had odds ratio = 48.8 (45.0-53.0) in statistically predicting poor health. CONCLUSION: This is the first study to report the population prevalence of coexisting intellectual disabilities and autism, and the substantial influence this double disadvantage has on general health status, apparent across the entire life course. This highlights a group in need of wider recognition for whom resources should be focused on and planned for, informed by evidence. Staff in services for people with either of these conditions need to be trained, equipped, resourced and prepared to address the challenge of working for people with this duality. This is essential, to address these substantial health inequalities.

Skeletal accumulation of fluorescently tagged zoledronate is higher in animals with early stage chronic kidney disease.

This work examines the skeletal accumulation of fluorescently tagged zoledronate in an animal model of chronic kidney disease. The results show higher accumulation in 24-h post-dose animals with lower kidney function due to greater amounts of binding at individual surfaces. INTRODUCTION: Chronic kidney disease (CKD) patients suffer from increased rates of skeletal-related mortality from changes driven by biochemical abnormalities. Bisphosphonates are commonly used in reducing fracture risk in a variety of diseases, yet their use is not recommended in advanced stages of CKD. This study aimed to characterize the accumulation of a single dose of fluorescently tagged zoledronate (FAM-ZOL) in the setting of reduced kidney function. METHODS: At 25 weeks of age, FAM-ZOL was administered to normal and CKD rats. Twenty-four hours later, multiple bones were collected and assessed using bulk fluorescence imaging, two-photon imaging, and dynamic histomorphometry. RESULTS: CKD animals had significantly higher levels of FAM-ZOL accumulation in the proximal tibia, radius, and ulna, but not in lumbar vertebral body or mandible, based on multiple measurement modalities. Although a majority of trabecular bone surfaces were covered with FAM-ZOL in both normal and CKD animals, the latter had significantly higher levels of fluorescence per unit bone surface in the proximal tibia. CONCLUSIONS: These results provide new data regarding how reduced kidney function affects drug accumulation in rat bone.

The organisation of critical care for burn patients in the UK: epidemiology and comparison of mortality prediction models.

In the UK, a network of specialist centres has been set up to provide critical care for burn patients. However, some burn patients are admitted to general intensive care units. Little is known about the casemix of these patients and how it compares with patients in specialist burn centres. It is not known whether burn-specific or generic risk prediction models perform better when applied to patients managed in intensive care units. We examined admissions for burns in the Case Mix Programme Database from April 2010 to March 2016. The casemix, activity and outcome in general and specialist burn intensive care units were compared and the fit of two burn-specific risk prediction models (revised Baux and Belgian Outcome in Burn Injury models) and one generic model (Intensive Care National Audit and Research Centre model) were compared. Patients in burn intensive care units had more extensive injuries compared with patients in general intensive care units (median (IQR [range]) burn surface area 16 (7-32 [0-98])% vs. 8 (1-18 [0-100])%, respectively) but in-hospital mortality was similar (22.8% vs. 19.0%, respectively). The discrimination and calibration of the generic Intensive Care National Audit and Research Centre model was superior to the revised Baux and Belgian Outcome in Burn Injury burn-specific models for patients managed on both specialist burn and general intensive care units.

Brief pain re-assessment provided more accurate prognosis than baseline information for low-back or shoulder pain.

BACKGROUND: Research investigating prognosis in musculoskeletal pain conditions has only been moderately successful in predicting which patients are unlikely to recover. Clinical decision making could potentially be improved by combining information taken at baseline and re-consultation. METHODS: Data from four prospective clinical cohorts of adults presenting to UK and Dutch primary care with low-back or shoulder pain was analysed, assessing long-term disability at 6 or 12 months and including baseline and 4-6 week assessments of pain. Baseline versus short-term assessments of pain, and previously validated multivariable prediction models versus repeat assessment, were compared to assess predictive performance of long-term disability outcome. A hypothetical clinical scenario was explored which made efficient use of both baseline and repeated assessment to identify patients likely to have a poor prognosis and decide on further treatment. RESULTS: Short-term repeat assessment of pain was better than short-term change or baseline score at predicting long-term disability improvement across all cohorts. Short-term repeat assessment of pain was only slightly more predictive of long-term recovery (c-statistics 0.78, 95% CI 0.74 to 0.83 and 0.75, 95% CI 0.69 to 0.82) than a multivariable baseline prognostic model in the two cohorts presenting such a model (c-statistics 0.71, 95% CI 0.67 to 0.76 and 0.72, 95% CI 0.66 to 0.78). Combining optimal prediction at baseline using a multivariable prognostic model with short-term repeat assessment of pain in those with uncertain prognosis in a hypothetical clinical scenario resulted in reduction in the number of patients with an uncertain probability of recovery, thereby reducing the instances where patients may be inappropriately referred or reassured. CONCLUSIONS: Incorporating short-term repeat assessment of pain into prognostic models could potentially optimise the clinical usefulness of prognostic information.

Otolaryngology residency education: a scoping review on the shift towards competency-based medical education.

BACKGROUND: Residency training programmes worldwide are experiencing a shift from the traditional time-based curriculum to competency-based medical education (CBME), due to changes in the healthcare system that have impacted clinical learning opportunities. Otolaryngology-Head and Neck Surgery (OTL-HNS) programmes are one of the first North American surgical specialties to adopt the new CBME curriculum. OBJECTIVE OF REVIEW: The purpose of this scoping review is to examine the literature pertaining to CBME in OTL-HNS programmes worldwide, to identify the tools that have been developed and identify potential barriers to the implementation of CBME. SEARCH STRATEGY: Four online databases, OVID MEDLINE (R) from 1946 to 5 August 2015, EMBASE 1974 to 5 August 2015, Cochrane and CINAHL databases up to 5 August 2015, were searched using key words related to OTL-HNS and CBME. EVALUATION METHOD: Two researchers independently reviewed the literature in a systematic manner and met to discuss and address any discrepancies at each step of the review process. RESULTS: Of the 207 publications identified in the initial search, 31 were included in this scoping review. Two key themes emerged from the literature: first, OTL-HNS programmes reported a need for new assessment tools that assess competency and also provide the learner with formative feedback. Second, although varieties of tools assessing both technical and non-technical skills have been developed, implementation of such tools has been met with some challenges. These challenges include a lack of faculty support, inadequate administrative support and a lack of knowledge on how to start the transition to CBME. CONCLUSIONS: This scoping review suggests that task-specific checklists, entrustment scales, evaluation portfolios from multiple assessments and faculty training sessions are key aspects to incorporate as OTL-HNS training programmes shift towards a CBME curriculum.

Direct-write 3D nanolithography at cryogenic temperatures.

Direct-write three-dimensional nanolithography is demonstrated using cryogenic electron beam-induced deposition (EBID). Cryogenic cooling and an electron beam were used to condense and expose the precursor methylcyclopentadienyl(trimethyl)platinum (MeCpPtMe(3)). The exposure process was modeled by Monte Carlo simulations of electron-condensate interactions, which were used to develop two approaches for the fabrication of three-dimensional self-supporting structures with incorporated gaps. Vertical and lateral resolutions of approximately 150 and 22 nm are demonstrated, and underlying mechanisms that limit resolution and throughput are identified. Resolution can be traded off for condensate exposure efficiency, which is shown to be up to four orders of magnitude greater than that of conventional, room temperature EBID.

Are childhood factors predictive of adult health literacy? A longitudinal birth cohort analysis.

Health literacy (HL), defined as the ability of an individual to understand and appraise health information to make informed decisions on their health, helps maintain and improve one's health and thus reduce the use of healthcare services. There is a recognised global effort to address insufficient HL in early life and understand how HL develops. This study examined the association of a range of factors including educational, speech and language ability, health and healthcare engagement, sleep problems, mental health, demographic, environmental, and maternal factors at different childhood stages (from 5 years to 11 years) with later adult HL at age 25. HL was measured using a HL ordinal score (insufficient, limited, or sufficient) derived from the European Literacy Survey Questionnaire-short version (HLS-EU-Q16) within a large UK based birth cohort (Avon Longitudinal Study of Parents and Children: ALSPAC study). Univariate proportional odds logistic regression models for the probability of having higher levels of HL were developed. Results of analysis of 4248 participants showed that poorer speech and language ability (aged 9 years, OR 0.18 95% CI 0.04 to 0.78), internalising in child (age 11 years, OR 0.62 95% CI 0.5 to 0.78), child depression (age 9 years, OR 0.67 95% CI 0.52 to 0.86), and the presence of maternal depression (child age 5, OR 0.80 95% CI 0.66 to 0.96), reduced the odds of sufficient HL when adult. Our results suggest some useful markers to identify children at potential risk of low HL that could be targeted for research into future interventions within school settings, for example, child's speech and language capability. In addition, this study identified child and maternal mental health as factors associated with later development of limited HL and future research should consider what potential mechanisms might explain this link.

Digital correction of motion artefacts in microscopy image sequences collected from living animals using rigid and nonrigid registration.

Digital image analysis is a fundamental component of quantitative microscopy. However, intravital microscopy presents many challenges for digital image analysis. In general, microscopy volumes are inherently anisotropic, suffer from decreasing contrast with tissue depth, lack object edge detail and characteristically have low signal levels. Intravital microscopy introduces the additional problem of motion artefacts, resulting from respiratory motion and heartbeat from specimens imaged in vivo. This paper describes an image registration technique for use with sequences of intravital microscopy images collected in time-series or in 3D volumes. Our registration method involves both rigid and nonrigid components. The rigid registration component corrects global image translations, whereas the nonrigid component manipulates a uniform grid of control points defined by B-splines. Each control point is optimized by minimizing a cost function consisting of two parts: a term to define image similarity, and a term to ensure deformation grid smoothness. Experimental results indicate that this approach is promising based on the analysis of several image volumes collected from the kidney, lung and salivary gland of living rodents.

Yakult: a role in combating multi-drug resistant Pseudomonas aeruginosa?

Presence of extremely drug resistant metallo-beta-lactamase (MBL VIM) Pseudomonas aeruginosa in a patient presenting with 54% deep-dermal and full-thickness flame burns to her neck, chest, upper abdomen and upper limbs, appeared to coincide with wound breakdown and non-healing. This organism was also seen to colonise the patient's gastrointestinal tract, which was thought to act as a reservoir for re-infection of her wounds. Oral treatment with a probiotic drink (Yakult yoghurt) was commenced in order to alter gut flora. Two weeks after this regimen began, P. aeruginosa grown from wound swabs was seen to change from multi-drug resistant to multi-drug sensitive strains. This change persisted through to patient discharge home from hospital. The temporal relationship seen between commencement of once-daily probiotic and change of the organism from multi-drug resistant to multi-drug sensitive suggests that this may have been an effective intervention.

The effects of refractive index heterogeneity within kidney tissue on multiphoton fluorescence excitation microscopy.

Although multiphoton fluorescence excitation microscopy has improved the depth at which useful fluorescence images can be collected in biological tissues, the reach of multiphoton fluorescence excitation microscopy is nonetheless limited by tissue scattering and spherical aberration. Scattering can be reduced in fixed samples by mounting in a medium whose refractive index closely matches that of the fixed material. Using optical 'clearing', the effects of refractive index heterogeneity on signal attenuation with depth are investigated. Quantitative measurements show that by mounting kidney tissue in a high refractive index medium, less than 50% of signal attenuates in 100 µm of depth.

The effects of spherical aberration on multiphoton fluorescence excitation microscopy.

Multiphoton fluorescence excitation microscopy is almost invariably conducted with samples whose refractive index differ from that of the objective immersion medium, conditions that cause spherical aberration. Due to the quadratic nature of multiphoton fluorescence excitation, spherical aberration is expected to profoundly affect the depth dependence of fluorescence excitation. In order to determine the effect of refractive index mismatch in multiphoton fluorescence excitation microscopy, we measured signal attenuation, photobleaching rates and resolution degradation with depth in homogeneous samples with minimal light scattering and absorption over a range of refractive indices. These studies demonstrate that signal levels and resolution both rapidly decline with depth into refractive index mismatched samples. Analyses of photobleaching rates indicate that the preponderance of signal attenuation with depth results from decreased rates of fluorescence excitation, even in a system with a descanned emission collection pathway. Similar results were obtained in analyses of fluorescence microspheres embedded in rat kidney tissue, demonstrating that spherical aberration is an important limiting factor in multiphoton fluorescence excitation microscopy of biological samples.

Perceptions of anonymised data use and awareness of the NHS data opt-out amongst patients, carers and healthcare staff.

BACKGROUND: England operates a National Data Opt-Out (NDOO) for the secondary use of confidential health data for research and planning. We hypothesised that public awareness and support for the secondary use of health data and the NDOO would vary by participant demography and healthcare experience. We explored patient/public awareness and perceptions of secondary data use, grouping potential researchers into National Health Service (NHS), academia or commercial. We assessed awareness of the NDOO system amongst patients, carers, healthcare staff and the public. We co-developed recommendations to consider when sharing unconsented health data for research. METHODS: A patient and public engagement program, co-created and including patient and public workshops, questionnaires and discussion groups regarding anonymised health data use. RESULTS: There were 350 participants in total. Central concerns for health data use included unauthorised data re-use, the potential for discrimination and data sharing without patient benefit. 94% of respondents were happy for their data to be used for NHS research, 85% for academic research and 68% by health companies, but less than 50% for non-healthcare companies and opinions varied with demography and participant group. Questionnaires showed that knowledge of the NDOO was low, with 32% of all respondents, 53% of all NHS staff and 29% of all patients aware of the NDOO. Recommendations to guide unconsented secondary health data use included that health data use should benefit patients; data sharing decisions should involve patients/public. That data should remain in close proximity to health services with the principles of data minimisation applied. Further, that there should be transparency in secondary health data use, including publicly available lists of projects, summaries and benefits. Finally, organisations involved in data access decisions should participate in programmes to increase knowledge of the NDOO, to ensure public members were making informed choices about their own data. CONCLUSION: The majority of participants in this study reported that the use of healthcare data for secondary purposes was acceptable when accessed by NHS. Academic and health-focused companies. However, awareness was limited, including of the NDOO. Further development of publicly-agreed recommendations for secondary health data use may improve both awareness and confidence in secondary health data use.

Health data from routine care can be pseudonymised (with a link remaining to the patient but identifying features removed) or anonymised (with identifying features removed and the link to the patient severed) and used for research and health planning; termed "secondary use". The National Health Service (NHS) is a single publicly-funded health service for the United Kingdom (UK). The NHS supports secondary data use with a National Data opt-out system. The potential benefits of data secondary use are clear but concerns have been raised. Although the Data Opt-Out is publicised, it is unclear how much public awareness there is of this scheme. We report a patient and publicly created and delivered series of activities including > 350 people; with young adults, patients, NHS staff and the public; to assess concerns, knowledge and acceptance of data sharing.Perceptions of and support for secondary health data use varied depending on who was asked (by age, gender) and their experience of health services (Staff member, patient, member of the public). Knowledge of schemes to limit secondary data use (such as the UK National Data Op-Out) was low, even among NHS staff. The main concerns of sharing health data included onward data use, the potential for discrimination and exploitation and commercial gain from data use with no benefit to patients. Despite this, most participants agreed with health data sharing with NHS, academic and commercial health-based entities. Agreed, co-created themes to increase the acceptability of health data secondary use included education about 'Opt-out' schemes, health service oversight of data use (as the most trusted partner), public and patient involvement in data sharing decisions and public transparency.

Sickness certification and the GP: what really happens in practice?

BACKGROUND: GPs typically sanction absence from work by issuing sickness certificates. There has been some debate recently about changing the way sickness certificates are issued and by whom. However, without understanding GPs' certification practices, their requirements in terms of training and education and how they feel the certification process should or should not be changed, measures aimed at improving the system are unlikely to succeed. OBJECTIVE: To investigate and describe British GPs' sickness certification practices. METHODS: A cross-sectional nationwide postal survey of 2154 UK GPs was conducted. GPs were asked about perceived certification practices, training in sickness certification, their opinions about the certification process and potential to improve the system. RESULTS: Adjusted response was 42% (n = 878). GPs do ask about a patient's work situation but lack training in sickness certification. GPs would like to maintain their role in sickness certification but felt there was scope for other health professionals to issue some sickness certificates. GPs report more frequent sickness certification for mental health and musculoskeletal conditions compared to any other condition. CONCLUSIONS: This study has highlighted the main issues that GPs face during a consultation where sickness certification is a possible outcome. Lack of training in certification was a recurrent theme. However, GPs felt there was scope to improve training and recommendations were made as to how this might be achieved. The survey has highlighted that GPs feel there are opportunities to improve the system and that other health professionals may play a role in the certification process.

Canine meningioma: a case report of a rare subtype and novel atlanto basioccipital surgical approach.

OBJECTIVE: To describe a novel histological subtype of skull base and cranial cervical meningioma operated upon through an uncommon atlanto basioccipital approach. STUDY DESIGN: Clinical case report. ANIMAL: A seven-year-old neutered female Boxer. METHODS: The dog was presented due to lethargic behavior, signs of head and neck pain, and ongoing tetraparesis. Neurological examination and magnetic resonance imaging led to diagnosis of a ventral spinal canal mass causing severe cord and brainstem compression and which required surgical management. RESULTS: The mass was approached through a ventral craniectomy extending cranially on the basioccipital bone. Extemporaneous cytological examination of the mass led to confirmation of neoplastic nature of the abnormal tissue. Cytoreduction of the mass was performed using multiple cycles of curettage, lavage and suction. Histopathological examination of the tumour was consistent with a papillary variant of meningioma. Adjuvant therapy was declined by the owners. The dog improved considerably in the postoperative period, however three months after surgery signs of recurrence led to euthanasia. CONCLUSIONS: Basioccipital craniectomy allowed a limited but sufficient approach for cytoreduction of a compressive meningioma of the brainstem and cranial cervical spinal cord. Papillary meningiomas are locally infiltrative and postoperative recurrence is common. CLINICAL RELEVANCE: Basioccipital approach combined with cranial atlanto corpectomy can be performed to relieve compression of the caudal brainstem and cranial cervical cord.

Delivery of ligands from sorting endosomes to late endosomes occurs by maturation of sorting endosomes.

After endocytosis, lysosomally targeted ligands pass through a series of endosomal compartments. The endocytic apparatus that accomplishes this passage may be considered to take one of two forms: (a) a system in which lysosomally targeted ligands pass through preexisting, long-lived early sorting endosomes and are then selectively transported to long-lived late endosomes in carrier vesicles, or (b) a system in which lysosomally targeted ligands are delivered to early sorting endosomes which themselves mature into late endosomes. We have previously shown that sorting endosomes in CHO cells fuse with newly formed endocytic vesicles (Dunn, K. W., T. E. McGraw, and F. R. Maxfield. 1989. J. Cell Biol. 109:3303-3314) and that previously endocytosed ligands lose their accessibility to fusion with a half-time of approximately 8 min (Salzman, N. H., and F. R. Maxfield. 1989. J. Cell Biol. 109:2097-2104). Here we have studied the properties of individual endosomes by digital image analysis to distinguish between the two mechanisms for entry of ligands into late endosomes. We incubated TRVb-1 cells (derived from CHO cells) with diO-LDL followed, after a variable chase, by diI-LDL, and measured the diO content of diI-containing endosomes. As the chase period was lengthened, an increasing percentage of the endosomes containing diO-LDL from the initial incubation had no detectable diI-LDL from the second incubation, but those endosomes that contained both probes showed no decrease in the amount of diO-LDL per endosomes. These results indicate that (a) a pulse of fluorescent LDL is retained by individual sorting endosomes, and (b) with time sorting endosomes lose the ability to fuse with primary endocytic vesicles. These data are inconsistent with a preexisting compartment model which predicts that the concentration of ligand in sorting endosomes will decline during a chase interval, but that the ability of the stable sorting endosome to receive newly endocytosed ligands will remain high. These data are consistent with a maturation mechanism in which the sorting endosome retains and accumulates lysosomally directed ligands until it loses its ability to fuse with newly formed endocytic vesicles and matures into a late endosome. We also find that, as expected according to the maturation model, new sorting endosomes are increasingly labeled during the chase period indicating that new sorting endosomes are continuously formed to replace those that have matured into late endosomes.(ABSTRACT TRUNCATED AT 400 WORDS)