Rochdale Infirmary

Following a previous description of nociceptive nerve fibre growth into usually aneural inner parts of painful intervertebral disc (IVD), this study has investigated whether nociceptive nerve ingrowth into painful IVD is stimulated by local production of neurotrophins. Immunohistochemistry and in situ hybridization have been used to investigate expression of the candidate neurotrophin, nerve growth factor (NGF), and its high- and low-affinity receptors trk-A and p75, respectively, in painful IVD excised for the management of low back pain. IVD from patients with back pain were of two types: those that when examined by discography reproduced the patient symptoms (pain level IVD) and those that did not (non-pain level IVD). Microvascular blood vessels accompanied nerve fibres growing into pain level IVD and these expressed NGF. The adjacent nerves expressed the high-affinity NGF receptor trk-A. These vessels entered the normally avascular IVD through the discal end plates. NGF expression was not identified in non-pain level or control IVD. Some non-pain level IVD had vessels within them, which entered through the annulus fibrosus. These did not express NGF nor did nerves accompany them. These findings show that nociceptive nerve ingrowth into painful IVD is causally linked with NGF production by blood vessels growing into the IVD, from adjacent vertebral bodies.

BACKGROUND: Ketogenic diets (KDs) are high in fat and low in carbohydrates and have been suggested to reduce seizure frequency in people with epilepsy. Such diets may be beneficial for children with drug-resistant epilepsy. This is an update of a review first published in 2003, and last updated in 2018. OBJECTIVES: To assess the effects of ketogenic diets for people with drug-resistant epilepsy. SEARCH METHODS: For this update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 26 April 2019) on 29 April 2019. The Cochrane Register of Studies includes the Cochrane Epilepsy Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), and randomised controlled trials (RCTs) from Embase, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional relevant studies. SELECTION CRITERIA: RCTs or quasi-RCTs of KDs for people of any age with drug-resistant epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently applied predefined criteria to extract data and evaluated study quality. We assessed the outcomes: seizure freedom, seizure reduction (50% or greater reduction in seizure frequency), adverse effects, cognition and behaviour, quality of life, and attrition rate. We incorporated a meta-analysis. We utilised an intention-to-treat (ITT) population for all primary analyses. We presented the results as risk ratios (RRs) with 95% confidence intervals (CIs). MAIN RESULTS: We identified 13 studies with 932 participants; 711 children (4 months to 18 years) and 221 adults (16 years and over). We assessed all 13 studies to be at high risk of performance and detection bias, due to lack of blinding. Assessments varied from low to high risk of bias for all other domains. We rated the evidence for all outcomes as low to very low certainty. Ketogenic diets versus usual care for children Seizure freedom (RR 3.16, 95% CI 1.20 to 8.35; P = 0.02; 4 studies, 385 participants; very low-certainty evidence) and seizure reduction (RR 5.80, 95% CI 3.48 to 9.65; P < 0.001; 4 studies, 385 participants; low-certainty evidence) favoured KDs (including: classic KD, medium-chain triglyceride (MCT) KD combined, MCT KD only, simplified modified Atkins diet (MAD) compared to usual care for children. We are not confident that these estimated effects are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea for both the intervention and usual care group, but the true effect could be substantially different (low-certainty evidence). Ketogenic diet versus usual care for adults In adults, no participants experienced seizure freedom. Seizure reduction favoured KDs (MAD only) over usual care but, again, we are not confident that the effect estimated is accurate (RR 5.03, 95% CI 0.26 to 97.68; P = 0.29; 2 studies, 141 participants; very low-certainty evidence). Adults receiving MAD most commonly reported vomiting, constipation and diarrhoea (very low-certainty evidence). One study reported a reduction in body mass index (BMI) plus increased cholesterol in the MAD group. The other reported weight loss. The true effect could be substantially different to that reported. Ketogenic diet versus ketogenic diet for children Up to 55% of children achieved seizure freedom with a classical 4:1 KD after three months whilst up to 85% of children achieved seizure reduction (very low-certainty evidence). One trial reported a greater incidence of seizure reduction with gradual-onset KD, as opposed to fasting-onset KD. Up to 25% of children were seizure free with MAD and up to 60% achieved seizure reduction. Up to 25% of children became seizure free with MAD and up to 60% experienced seizure reduction. One study used a simplified MAD (sMAD) and reported that 15% of children gained seizure freedom rates and 56% achieved seizure reduction. We judged all the evidence described as very low certainty, thus we are very unsure whether the results are accurate. The most commonly reported adverse effects were vomiting, constipation and diarrhoea (5 studies, very low-certainty evidence). Two studies reported weight loss. One stated that weight loss and gastrointestinal disturbances were more frequent, with 4:1 versus 3:1 KD, whilst one reported no difference in weight loss with 20 mg/d versus 10 mg/d carbohydrates. In one study, there was a higher incidence of hypercalcuria amongst children receiving classic KD compared to MAD. All effects described are unlikely to be accurate. Ketogenic diet versus ketogenic diet for adults One study randomised 80 adults (aged 18 years and over) to either MAD plus KetoCal during the first month with MAD alone for the second month, or MAD alone for the first month followed by MAD plus KetoCal for the second month. No adults achieved seizure freedom. More adults achieved seizure reduction at one month with MAD alone (42.5%) compared to MAD plus KetoCal (32.5%), however, by three months only 10% of adults in both groups maintained seizure reduction. The evidence for both outcomes was of very low certainty; we are very uncertain whether the effects are accurate. Constipation was more frequently reported in the MAD plus KetoCal group (17.5%) compared to the MAD only group (5%) (1 study, very low-certainty evidence). Diarrhoea and increase/change in seizure pattern/semiology were also commonly reported (17.5% to 20% of participants). The true effects of the diets could be substantially different to that reported. AUTHORS' CONCLUSIONS: The evidence suggests that KDs could demonstrate effectiveness in children with drug-resistant epilepsy, however, the evidence for the use of KDs in adults remains uncertain. We identified a limited number of studies which all had small sample sizes. Due to the associated risk of bias and imprecision caused by small study populations, the evidence for the use of KDs was of low to very low certainty. More palatable but related diets, such as the MAD, may have a similar effect on seizure control as the classical KD, but could be associated with fewer adverse effects. This assumption requires more investigation. For people who have drug-resistant epilepsy or who are unsuitable for surgical intervention, KDs remain a valid option. Further research is required, particularly for adults with drug-resistant epilepsy.

BACKGROUND: Despite growing evidence of the effectiveness of cognitive-behavioural therapy (CBT) for psychosis, typically only about 50% of patients show a positive response to treatment. This paper reports the first comprehensive investigation of factors which predict treatment outcome. METHOD: In a randomised controlled trial of CBT for medication-resistant psychosis (see Part I) measures were taken at baseline of demographic, clinical and cognitive variables. Changes over time were assessed on the Brief Psychiatric Rating Scale and the relationship between potential predictor variables and outcome was investigated using analysis of variance and covariance. RESULTS: A number of baseline variables were identified as predictors of good outcome in the CBT group. Key predictors were a response indicating cognitive flexibility concerning delusions (P = 0.005) and the number of recent admissions (P = 0.002). Outcome was less predictable in the control group and was not predicted by any cognitive variable. CONCLUSIONS: Good outcome is strongly predicted in patients with persistent delusions by a cognitive measure, while this was not the case in controls. Thus we argue that positive outcome in CBT is due in part to specific effects on delusional thinking.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist.

In 277 consecutive episodes of suspected upper gastrointestinal bleeding, lesions bearing stigmata of recent haemorrhage (stigmata) were found by endoscopy in 110 (47%) out of 233 patients who were judged to have bled; 78 (33%) had lesions without stigmata, and in 45 (19%) no lesion was seen. Results in 176 entirely unselected admissions for upper gastrointestinal bleeding were similar.Forty-eight chronic duodenal and 41 chronic gastric ulcers were identified by endoscopy. Stigmata were found in 27 (56%) and 33 (80%) of these cases respectively. Sixteen patients had multiple lesions, and in 12 (75%) the presence of stigmata permitted diagnosis of the source of the haemorrhage. Stigmata were more likely to be seen in cases of duodenal ulcer, Mallory-Weiss lesions, and oesophageal varices when endoscopy was performed within 12 hours of bleeding, but were as common in cases of gastric ulcer after longer intervals.In the absence of stigmata one out of 21 patients with duodenal ulcer had further haemorrhage and one other needed emergency surgery; no patient with gastric ulcer had further haemorrhage or needed emergency surgery. In contrast, when stigmata were present 15 of the 27 patients with duodenal ulcer (56%) had further haemorrhage and 17 (63%) needed emergency surgery; of the 33 patients with gastric ulcer, 10 (30%) had further haemorrhage and 15 (45%) required emergency surgery. Superficial mucosal lesions may have been the source of haemorrhage when an ulcer unmarked by stigmata was seen at endoscopy. Stigmata were superior to any other single factor or combination of factors in predicting rebleeding and the need for emergency surgery.

Three groups of men and women employed at a Rochdale asbestos textile factory have been followed to 30 June 1983 and their mortality compared with that expected at national and Rochdale rates, i.e. (i) 145 men first employed before 1933 who had served 20 yr or more in scheduled areas, (ii) 283 women first employed in 1933 or later who had served ten or more years in scheduled areas, and (iii) a principal cohort of 3211 men first employed between 1933 and 1974. Systematic measurements of the ambient pollution in the workplace have been made since 1951 either in terms of particles ml −1 or of fibres (of specified size) ml −1 and estimates have been made of the average concentration of particles (or fibres) to which individual members of the principal cohort were exposed. From these data estimates have been made of the quantitative relationship between ambient exposure and mortality from lung cancer and mesothelioma. These results, together with other published data, suggest that the lung cancer rate among chrysotile textile workers is approximately doubled following a cumulative exposure of 100 fibre ml −1 yr, irrespective of age at first exposure. Chrysotile asbestos was used in the factory throughout, but some crocidolite (approx. 5.0%) was used between 1932 and 1968 and this may have contributed, perhaps substantially, to the observed mesothelioma risk. For the purpose of risk prediction we have rather arbitrarily assumed that the mesothelioma risk caused by a similar concentration of pure chrysotile would have been roughly half that observed in this factory. This implies that 35 yr chrysotile exposure at an average concentration of 1 fibre ml −1 might eventually cause mesothelioma in about one worker in 200 if exposure began at age 20, although the risk would be substantially lower if exposure began later in life. If enforcement of the current U.K. control limit for chrysotile of 0.5 fibre ml −1 results in an average level of 0.25 fibre ml −1 in the workplace, these estimates suggest that the risk of eventually developing asbestos-related lung cancer or mesothelioma to a man first employed at age 20 who works in the asbestos textile industry for 35 yr may be about 0.8%. This prediction is of doubtful accuracy, however, as the exposure data were derived largely from static particle counts and the correlation between particle and fibre counts is poor.

BACKGROUND: The UK is a multicultural, multilingual society and the majority of paediatric speech and language therapists in England have at least one bilingual child on their caseload. There are many imperatives driving the profession to provide an equitable service for bilingual children. Evidence is beginning to emerge, however, that bilingual children with specific language impairment are not being identified and are, therefore, not accessing services. The situation facing clinicians in the UK is not unique: it is mirrored around the world. AIMS: This paper reviews the literature relating to speech and language services for bilingual children and begins by providing an overview of the forces driving the need to provide equity of service. All aspects of the therapeutic process are then examined, from referral to therapy, in order to identify features that are regarded as best practice. Whilst the focus is on delivery of services in the UK, research findings from around the world are considered. MAIN CONTRIBUTION: Certain themes emerged during the review and their implications are discussed. In particular, the need for assessment tools, training and research is highlighted. CONCLUSIONS: Features indicative of best practice are highlighted and tentative suggestions made that would enable services to address the challenges of serving bilingual paediatric caseloads.

PURPOSE OF REVIEW: This review summarizes the current knowledge about hypoxia and hypoxia-inducible factor-1 (HIF-1) for chondrocyte survival, energy generation and matrix synthesis of articular chondrocytes during cartilage homeostasis and disease. RECENT FINDINGS: In recent years increasing evidence of a pivotal role of hypoxia and the transcription factor HIF-1alpha in cartilaginous tissues has been published. Growth plates with functionally inactivated hypoxia-inducible factor-1alpha display great defects in their central areas caused by massive cell death. This very important observation indicates that hypoxia-inducible factor-1alpha is absolutely necessary for chondrocytes to survive extremely low oxygen tensions. Furthermore, hypoxia-inducible factor-1alpha has been shown to have very important functions for the regulation of glucose transport, anaerobic energy generation and matrix synthesis by articular chondrocytes. Besides hypoxia, other factors such as proinflammatory mediators and mechanical load have been shown to increase hypoxia-inducible factor-1alpha activity in articular chondrocytes. All these factors are known to be involved in the pathogenesis of osteoarthritis. Thus, a dependence of osteoarthritis chondrocytes on hypoxia-inducible factor-1alpha to survive and function properly is a reasonable assumption. SUMMARY: Low oxygen tensions and hypoxia-inducible factor-1alpha are important factors in articular chondrocyte behaviour during cartilage homeostasis and osteoarthritis. Hypoxia-inducible factor-1alpha is a highly conserved transcription factor that has key functions in controlling energy generation, cell survival and matrix synthesis by articular and growth-plate chondrocytes.

Abstract Self‐reported stressors, coping strategies and stress‐related outcomes were explored among 68 direct‐care staff working in two networks of small staffed houses for people with learning disabilities. The two networks tended to have lower rates of staff turnover, and staff tended to be older, more qualified and more likely to have dependants, than staff in UK community services reported in previous studies. Staff in Network 2 rated several stressors as more stressful and reported themselves as experiencing greater general distress and work‐related stress, than staff in Network 1. Multiple regressions revealed that: (1) stressors relating to the emotional impact of the work, violent service user behaviour and the use of a wishful thinking coping strategy were associated with perceived work stress; (2) stressors relating to the conflict of work with personal or family demands, and the use of a wishful thinking coping strategy, were associated with symptoms of general distress; (3) perceived work stress, together with uncertainty concerning job tasks and limited opportunities for personal advancement, were perceived to have a high impact on work

Averting human‐induced extinctions will require strong policy commitments that comprehensively address threats to species. A new Global Biodiversity Framework is currently being negotiated by the world’s governments through the Convention on Biological Diversity. Here we explored how the suggested targets in this framework could contribute to reducing threats to threatened vertebrates, invertebrates, and plants, and assessed the importance of a proposed target to implement recovery actions for threatened species. Although many of the targets benefit species, we found that extinction risk for over half (57%) of threatened species would not be reduced sufficiently without a target promoting recovery actions, including ex situ conservation, reintroductions, and other species‐specific interventions. A median of 54 threatened species per country require such actions, and most countries of the world hold such species. Preventing future human‐induced extinctions requires policy commitments to implement targeted recovery actions for threatened species in addition to broader efforts to mitigate threats, underpinned by transformative change.

Abstract Women with abnormal smears have an increased risk of developing cervical cancer. During the 8 years following conservative treatment of cervical intraepithelial neoplasia (CIN), their risk of invasive cervical cancer is about 5 times greater than that of the general population. Human papillomavirus (HPV) has been associated with the natural history of both CIN and cervical cancer. To date, there have been no published reports on the predictive value of HPV testing in the treatment outcome of CIN. A prospective, multi‐center, cohort study was conducted on women in the Northwest of England who were attending for treatment of CIN. They were asked to complete a questionnaire, which included a detailed smoking history. Pre‐ and post‐treatment HPV testing was performed on cervical biopsies and cervical swab, being taken with the first follow‐up smear at 6 months. A nested case‐control analysis was performed, cases being defined as women who developed CIN within the 2 years of treatment and controls being sampled from those who did not experience treatment failure within 2 years. Multiple conditional logistic regression is used to study the factors associated with treatment failure of CIN. The cohort included 958 women of whom 77 (8%) experienced treatment failure (cases). Two controls were matched to each case (154). Smoking status was significantly associated with CIN treatment failure( p = 0.0013). Current smokers had a 3‐fold increased risk of treatment failure of CIN as compared to non‐smokers (95% CI 1.65 to 5.91). Five hundred twenty‐five women underwent HPV sampling following treatment, of whom 47 (8.9%) developed further CIN. Post‐treatment positive HPV testing was found to be strongly associated with treatment failure of CIN (OR 23.3; 95% CI 3.15–172.1). In 11/45 cases with negative smear at first follow‐up, the HPV test was positive. The combination of both HPV and cytology in the first follow‐up visit predicted treatment failure in 72% of the cases. Cigarette smoking is a factor, which, independently of HPV infection, influences the treatment outcome of CIN. Smokers and those who are HPV positive during follow‐up appear to require longer, more intensive follow‐up. HPV testing requires careful consideration as part of routine follow‐up protocol following treatment of CIN. © 2002 Wiley‐Liss, Inc.

ABSTRACT A group of 379 men who had worked at an asbestos textile factory for at least 10 years has been followed up. The prevalence of crepitations, 9possible asbestosis9, certified asbestosis, small opacities in the chest radiograph and values of lung function have been related to dust levels. The type of asbestos processed was predominantly chrysotile although a substantial amount of crocidolite had also been used in the past. There was a higher prevalence of crepitations than had been observed previously at the same factory. The presence of crepitations is not a specific effect of asbestos exposure and 9possible asbestosis9, a combined judgement of two physicians on whether a man had developed signs which might be attributable to early asbestosis, was preferred. Fifty per cent of men with a diagnosis of possible asbestosis were certified as suffering from asbestosis by the pneumoconiosis Medical Panel within 3-5 yr. The most reliable data relate to men first employed after 1950; 6·6% of men in this group had possible asbestosis after an average length of follow-up of 16 yr and an average exposure to 5 fibre/cm³ where the dust levels were determined by static area samplers. The forced expiratory volume and forced vital capacity declined significantly with exposure, after allowing for age and height, but there was no decline in the total lung capacity. The transfer factor also declined with exposure, but not to a statistically significant extent. The non-smokers and light smokers as a group had less crepitations, asbestosis and small opacities on the chest radiograph than heavier smokers with similar exposure. Combining dust concentrations to form the cumulative dose may not be completely satisfactory, and a family of measures was investigated which allows for elimination of dust from the lungs and includes the cumulative dose as a special case. Because the rate of elimination of dust from the lungs is unknown and cannot be estimated from the data, this approach leads to a wide range of possible interpretations of the data; for example the concentration such that possible asbestosis occurs in no more than 1% of men after 40 years9 exposure could be as high as 1·1 fibres/cm³ or may have to be as low as 0·3 fibres/cm³. This range is wide because the data relate to higher dust levels, and a shorter period of follow-up. Until data are available on groups exposed to lower levels it will not be possible to assess the effects of the current standard with any certainty. However, the results of this study show that it is important to continue to reduce dust levels to values as low as possible.

One hundred and eighty-eight Asian immigrants and 78 Caucasian control subjects were examined clinically and biochemically for evidence of vitamin D deficiency. An incidence of 30 per cent of oven rickets and osteomalacia was found in children and adult women. When abnormal biochemical findings were included, the incidence of apparent vitamin D deficiency rose to 74 per cent amongst the children and 53 per cent amongst the adults. The condition is shown to be responsive to treatment with vitamin D. The aetiology of the disease is discussed. No certain cause can be identified but there is no evidence to suggest that the condition is directly due to the im of these people into Britain. It is recommended that the Asian section of our community should increase the vitamin D content of their diet.

Background: Female Genital Mutilation/Cutting (FGM/C) is the procedure of removing healthy external genitalia from girls/women for socio-cultural reasons. There is much scientific literature on the adverse physical health complications that can result from having FGM/C, but little is known about its psychological impact and treatment. Objective: To identify psychological problems that may follow from a woman having FGM/C and success of treatment herein, and relate findings to the role of the maternity care professional. Study design: A structured narrative review, which identified 10 studies, was carried out. Findings: Eight of ten studies reported psychological consequences, such as Post-Traumatic Stress Disorder (PTSD) and affective disorders. Also identified were socio-cultural differences in the meaning of perceived consequences for different individuals. Two studies reported inconclusive results regarding the psychological impact of FGM/C on women’s lives. Key conclusion: While these findings provide an indication of adverse psychological effects of women/ girls having FGM/C, more studies are needed. In particular, studies that focus on the role that cutting extent, circumstances surrounding the cutting, and girls’ level of knowledge of what was going to take place, and their relationships to psychological outcomes. Implications for Practice: Raising awareness of the risk of negative psychological consequences is important, with maternal health care professionals requiring training on how to treat and care for women/girls who are suffering problems that result from having FGM/C.

Background Risk factors for severe COVID-19 include older age, male sex, obesity, black or Asian ethnicity and underlying medical conditions. Whether these factors also influence susceptibility to developing COVID-19 is uncertain. Methods We undertook a prospective, population-based cohort study (COVIDENCE UK) from 1 May 2020 to 5 February 2021. Baseline information on potential risk factors was captured by an online questionnaire. Monthly follow-up questionnaires captured incident COVID-19. We used logistic regression models to estimate multivariable-adjusted ORs (aORs) for associations between potential risk factors and odds of COVID-19. Results We recorded 446 incident cases of COVID-19 in 15 227 participants (2.9%). Increased odds of developing COVID-19 were independently associated with Asian/Asian British versus white ethnicity (aOR 2.28, 95% CI 1.33 to 3.91), household overcrowding (aOR per additional 0.5 people/bedroom 1.26, 1.11 to 1.43), any versus no visits to/from other households in previous week (aOR 1.31, 1.06 to 1.62), number of visits to indoor public places (aOR per extra visit per week 1.05, 1.02 to 1.09), frontline occupation excluding health/social care versus no frontline occupation (aOR 1.49, 1.12 to 1.98) and raised body mass index (BMI) (aOR 1.50 (1.19 to 1.89) for BMI 25.0–30.0 kg/m 2 and 1.39 (1.06 to 1.84) for BMI &gt;30.0 kg/m 2 versus BMI &lt;25.0 kg/m 2 ). Atopic disease was independently associated with decreased odds (aOR 0.75, 0.59 to 0.97). No independent associations were seen for age, sex, other medical conditions, diet or micronutrient supplement use. Conclusions After rigorous adjustment for factors influencing exposure to SARS-CoV-2, Asian/Asian British ethnicity and raised BMI were associated with increased odds of developing COVID-19, while atopic disease was associated with decreased odds. Trial registration number ClinicalTrials.gov Registry ( NCT04330599 ).

AIM: Thiamine-responsive megaloblastic anaemia syndrome (TRMA) is the association of diabetes mellitus, anaemia and deafness, due to mutations in SLC19A2, encoding a thiamine transporter protein. This is a unique monogenic form of vitamin-dependent diabetes for which there is limited long-term data. We aimed to study genotype-phenotype relationships and long-term follow-up in our cohort. METHODS: We have studied 13 patients from seven families and have follow-up data for a median of 9 y (2-30 y). RESULTS: All patients originated from Kashmir or Punjab, and presented with non-immune, insulin-deficient diabetes mellitus, sensorineural deafness and a variable anaemia in the first 5 y of life, the anaemia progressing to megaloblastic and sideroblastic changes in the bone marrow. The anaemia and diabetes mellitus responded to oral thiamine hydrochloride 25 mg/d, but during puberty thiamine supplements became ineffective, and almost all patients require insulin therapy and regular blood transfusions in adulthood. All patients are homozygous for mutations in the SLC19A2 gene. We have identified a novel missense mutation (T158R) that was excluded in 100 control alleles. CONCLUSION: Diabetes in this syndrome is due to an insulin insufficiency that initially responds to thiamine supplements; however, most patients become fully insulin dependent after puberty. A mutation screening strategy is feasible and likely to identify mutations in almost all cases.

It has been suggested that challenging behaviour in people with dementia reflects a person's pre-morbid personality traits and a number of studies have explored this hypothesis. However, inconsistencies in outcome between studies suggest a need to review the available evidence systematically. As a result, major bibliographic databases were searched for studies examining the relationship between pre-morbid personality and challenging behaviour in order to conduct a systematic review. We included all English language studies published in referenced journals that assessed pre-morbid personality via a valid comprehensive personality measure, and also explored a relationship with challenging behaviour in people with dementia. A total of 18 studies were identified that covered a wide range of challenging behaviours including 'wandering', affective states, aggression, anxiety and delusions/hallucinations. Studies were assessed for their methodological quality and statistical findings. Studies lacked representative samples, were affected by confounding variables and suffered from small sample sizes. However, 72% of the studies reported significant relationships between pre-morbid personality and behaviour. In terms of specific relationships, the strongest evidence was found for a positive relationship between pre-morbid neuroticism and mood, and aggression and overall behavioural acts, thus supporting the inclusion of personality as one factor in the formulation of behaviour (Ballard, C., O'Brien, J., James, I., & Swann, A. (2001). Dementia: Management of Behavioural and Psychological Symptoms. Oxford: Oxford University Press; Kitwood, T. (1993). Person and process in dementia: Editorial. International Journal of Geriatric Psychiatry, 1, 541-545).

The 3q29 microdeletion syndrome is caused by a recurrent 1.6 Mb deletion of the 3q subtelomeric region. Though sometimes visible on routine microscopy, the deletion is detected more reliably using subtelomeric fluorescence in-situ hybridization (FISH) or molecular karyotyping. The clinical features associated with a 3q29 microdeletion are variable and include developmental delay, autistic features, skeletal abnormalities and dysmorphic facial features with a relatively long face, long nose with a high bridge and broad tip, short philtrum and large ears. Orofacial clefting, cardiac defects, ocular anomalies and genitourinary malformations have been reported occasionally. We report a three generation family where four individuals were confirmed to have a 3q29 microdeletion and compare their clinical features to those of previously reported patients. This family shows that the learning difficulties associated with a 3q29 deletion may be relatively mild. The history of a severe depressive disorder commencing in adulthood in the affected grandmother also supports previous studies linking the 3q29 region to bipolar disorder and links with the observation of Digilio et al. (2009) who also reported a history of depression in an adult woman with a similar deletion.

Twenty‐one South Asian adolescents and adults with intellectual disabilities were interviewed regarding eight areas of their lives: accommodation, individual support, day services, service support, social and recreational activities, friendships and relationships, ethnic and racial identity, and racism and stigma. All interviews were coded for user satisfaction with these aspects of their lives, and content‐analysed to draw out relevant themes. From the interviews, it is clear that South Asian adolescents and adults have a strong and positive sense of their ethnic and racial identity, and that they are generally satisfied with their home and family circumstances. However, people with intellectual disabilities from South Asian communities experience pervasive racism and stigma throughout all areas of their lives. Consequences of this double discrimination include a lack of culturally appropriate services, limited friendships and closer relationships, and a lack of meaningful leisure activities. Implications of these findings for services are discussed.

The aim of the current study was to investigate positional specific physical performance and external load responses to short term fixture congestion in English professional soccer. A total of 515 match observations were categorised as G1: the first game in a week with >4 days following a previous game, G2: the second game in a week played <4 days since G1, and G3: the third game in a week played with <4 days between each of the previous games. Global positioning system and accelerometer-based metrics were partitioned into fifteen-minute epochs. These data were then analysed using a linear mixed model to assess both the within and between game positional differences. Total, low-intensity (<4.0 m·s−1), medium-intensity (MID; 4.0–5.5 m·s−1), and sprint distance (>7.0 m·s−1) were significantly different across games. No between game positional differences were identified; however, within match position specific differences were observed for measures of MID and HID. No significant differences were evident for accelerometer derived metrics between games or across positions. The current data suggests that the use of fifteen minute within game epochs enables the detection of alterations in physical output during congested schedules. The observed within game positional differences has implications for player specific conditioning and squad rotation strategies.