Decompressive craniectomy to cranioplasty: a retrospective observational study using Hospital Episode Statistics in England.

Objectives: To investigate the longitudinal trends of decompressive craniectomy (DC) following traumatic brain injury (TBI) or stroke and explore whether the timing of cranial reconstruction affected revision or removal rates using Hospital Episode Statistics (HES) between 2014 and 2019. Design: Retrospective observational cohort study using HES. The time frame definitions mirror those often used in clinical practice. Setting: HES data from neurosurgical centres in England. Participants: HES data related to decompressive craniectomy procedures and cranioplasty following TBI or stroke between 2014 and 2019. Main outcome measures: The primary outcome was the timing and rate of revision/removal compared with cranioplasty within <12 weeks to ≥12 weeks. Results: There were 4627 DC procedures, of which 1847 (40%) were due to head injury, 1116 (24%) were due to stroke, 728 (16%) were due to other cerebrovascular diagnoses, 317 (7%) had mixed diagnosis and 619 (13%) had no pre-specified diagnoses. The number of DC procedures performed per year ranged from 876 in 2014-2015 to 967 in 2018-2019. There were 4466 cranioplasty procedures, with 309 (7%) revisions and/or removals during the first postoperative year. There was a 33% increase in the overall number of cranioplasty procedures performed within 12 weeks, and there were 1823 patients who underwent both craniectomy and cranioplasty during the study period, with 1436 (79%) having a cranioplasty within 1 year. However, relating to the timing of cranial reconstruction, there was no evidence of any difference in the rate of revision or removal surgery in the early timing group (6.5%) compared with standard care (7.9%) (adjusted HR 0.93, 95% CIs 0.61 to 1.43; p=0.75). Conclusions: Overall number of craniectomies and the subsequent requirements for cranioplasty increased steadily during the study period. However, relating to the timing of cranial reconstruction, there was no evidence of an overall difference in the rate of revision or removal surgery in the early timing group.

The reliability of pseudoneglect is task dependent.

Bisection tasks that require individuals to identify the midpoint of a line are often used to assess the presence of biases to spatial attention in both healthy and patient populations. These tasks have helped to uncover a phenomenon called pseudoneglect, a bias towards the left-side of space in healthy individuals. First identified in the tactile domain, pseudoneglect has been subsequently demonstrated in other sensory modalities such as vision. Despite this, the specific reliability of pseudoneglect within individuals across tasks and time has been investigated very little. In this study, we investigated the reliability of response bias within individuals across four separate testing sessions and during three line bisection tasks: landmark, line bisection and tactile rod bisection. Strong reliability was expected within individuals across task and session. Pseudoneglect was found when response bias was averaged across all tasks, for the entire sample. However, individual data showed biases to both left and right, with some participants showing no clear bias, demonstrating individual differences in bias. Significant, cross-session within-individual reliability was found for the landmark and tactile rod bisection tasks respectively, but no significant reliability was observed for the line bisection task. These results highlight the inconsistent nature of pseudoneglect within individuals, particularly across sensory modality. They also provide strong support for the use of the landmark task as the most reliable measure of pseudoneglect.

Pattern contrast influences wariness in naïve predators towards aposematic patterns.

An apparent and common feature of aposematic patterns is that they contain a high level of achromatic (luminance) contrast, for example, many warning signals combine black spots and stripes with a lighter colour such as yellow. However, the potential importance of achromatic contrast, as distinct from colour contrast, in reducing predation has been largely overlooked. Here, using domestic chicks as a model predator, we manipulated the degree of achromatic contrast in warning patterns to test if high luminance contrast in aposematic signals is important for deterring naïve predators. We found that the chicks were less likely to approach and eat prey with high contrast compared to low contrast patterns. These findings suggest that aposematic prey patterns with a high luminance contrast can benefit from increased survival through eliciting unlearned biases in naïve avian predators. Our work also highlights the importance of considering luminance contrast in future work investigating why aposematic patterns take the particular forms that they do.

Whole-genome sequencing reveals clinically relevant insights into the aetiology of familial breast cancers.

BACKGROUND: Whole-genome sequencing (WGS) is a powerful method for revealing the diversity and complexity of the somatic mutation burden of tumours. Here, we investigated the utility of tumour and matched germline WGS for understanding aetiology and treatment opportunities for high-risk individuals with familial breast cancer. PATIENTS AND METHODS: We carried out WGS on 78 paired germline and tumour DNA samples from individuals carrying pathogenic variants in BRCA1 (n = 26) or BRCA2 (n = 22) or from non-carriers (non-BRCA1/2; n = 30). RESULTS: Matched germline/tumour WGS and somatic mutational signature analysis revealed patients with unreported, dual pathogenic germline variants in cancer risk genes (BRCA1/BRCA2; BRCA1/MUTYH). The strategy identified that 100% of tumours from BRCA1 carriers and 91% of tumours from BRCA2 carriers exhibited biallelic inactivation of the respective gene, together with somatic mutational signatures suggestive of a functional deficiency in homologous recombination. A set of non-BRCA1/2 tumours also had somatic signatures indicative of BRCA-deficiency, including tumours with BRCA1 promoter methylation, and tumours from carriers of a PALB2 pathogenic germline variant and a BRCA2 variant of uncertain significance. A subset of 13 non-BRCA1/2 tumours from early onset cases were BRCA-proficient, yet displayed complex clustered structural rearrangements associated with the amplification of oncogenes and pathogenic germline variants in TP53, ATM and CHEK2. CONCLUSIONS: Our study highlights the role that WGS of matched germline/tumour DNA and the somatic mutational signatures can play in the discovery of pathogenic germline variants and for providing supporting evidence for variant pathogenicity. WGS-derived signatures were more robust than germline status and other genomic predictors of homologous recombination deficiency, thus impacting the selection of platinum-based or PARP inhibitor therapy. In this first examination of non-BRCA1/2 tumours by WGS, we illustrate the considerable heterogeneity of these tumour genomes and highlight that complex genomic rearrangements may drive tumourigenesis in a subset of cases.

Development of the MapMe intervention body image scales of known weight status for 4-5 and 10-11 year old children.

Background: Parents tend to visually assess children to determine their weight status and typically underestimate child body size. A visual tool may aid parents to more accurately assess child weight status and so support strategies to reduce childhood overweight. Body image scales (BIS) are visual images of people ranging from underweight to overweight but none exist for children based on UK criteria. Our aim was to develop sex- and age-specific BIS for children, based on British growth reference (UK90) criteria. Methods: BIS were developed using 3D surface body scans of children, their associated weight status using UK90 criteria from height and weight measurements, and qualitative work with parents and health professionals. Results: Height, weight and 3D body scans were collected (211: 4-5 years; 177: 10-11 years). Overall, 12 qualitative sessions were held with 37 participants. Four BIS (4-5-year-old girls and boys, 10-11-year-old girls and boys) were developed. Conclusions: This study has created the first sex- and age-specific BIS, based on UK90 criteria. The BIS have potential for use in child overweight prevention and management strategies, and in future research. This study also provides a protocol for the development of further BIS appropriate to other age groups and ethnicities.

Depth perception in disparity-defined objects: finding the balance between averaging and segregation.

Deciding what constitutes an object, and what background, is an essential task for the visual system. This presents a conundrum: averaging over the visual scene is required to obtain a precise signal for object segregation, but segregation is required to define the region over which averaging should take place. Depth, obtained via binocular disparity (the differences between two eyes' views), could help with segregation by enabling identification of object and background via differences in depth. Here, we explore depth perception in disparity-defined objects. We show that a simple object segregation rule, followed by averaging over that segregated area, can account for depth estimation errors. To do this, we compared objects with smoothly varying depth edges to those with sharp depth edges, and found that perceived peak depth was reduced for the former. A computational model used a rule based on object shape to segregate and average over a central portion of the object, and was able to emulate the reduction in perceived depth. We also demonstrated that the segregated area is not predefined but is dependent on the object shape. We discuss how this segregation strategy could be employed by animals seeking to deter binocular predators.This article is part of the themed issue 'Vision in our three-dimensional world'.

Women and their birth partners' experiences following a primary postpartum haemorrhage: a qualitative study.

BACKGROUND: Postpartum haemorrhage (PPH) is a common obstetric complication. Rates of PPH are increasing in a number of developed countries. This is concerning as PPH is recognised as a leading cause of maternal morbidity and mortality which includes psychological and emotional distress. There is limited understanding of the emotional impact of PPH experienced by women and their birth partners. This study qualitatively describes the experiences of women and their birth partners who experienced a primary PPH. METHODS: Semi-structured interview study. Couples were recruited via maximum variation sampling, which, by purposive sampling drew participants from three groups depending on the degree of PPH: minor (500-1000 ml), moderate (1000-2000 ml) and severe (>2000 ml). Interviews took place from 4 to 14 months post birth, and data were analysed via Framework analysis. RESULTS: In this qualitative study, 11 women and six partners were interviewed. Data were organised into four interrelated themes; Control, Communication, Consequence, Competence. Just over half of the women and their birth partners were unaware they had a PPH, and would have preferred more information either at the time or in the postnatal period. The findings suggest that birth partners also required more information, especially if separated from their partner during the PPH. CONCLUSIONS: This study provides valuable insights into women's reports of their feelings and experiences during and after a PPH, and how their partners feel having observed a PPH. This study suggests that women who have had a PPH of any volume would like more information. Further investigations into the timings, methods and effectiveness of discussions following a PPH are recommended.

Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium.

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Rat-specific IgG and IgG4 antibodies associated with inhibition of IgE-allergen complex binding in laboratory animal workers.

OBJECTIVES: The relationship between exposure to rodent allergens and laboratory animal allergy is complex; at highest allergen exposures there is an attenuation of sensitisation and symptoms which are associated with increased levels of rat-specific immunoglobulin (Ig)G and IgG4 antibodies. We set out to examine whether the increased levels of rat-specific IgG and IgG4 antibodies that we have previously observed at high allergen exposure in our cohort of laboratory animal workers play a functional role through blockage of the binding of IgE-allergen complex binding to CD23 receptors on B cells. METHODS: Cross-sectional survey of laboratory animal workers (n=776) in six UK pharmaceutical companies were surveyed. IgE-allergen complex binding to B cells was measured in 703 (97.9%) eligible employees; their exposure was categorised by either job group or number of rats handled daily. RESULTS: We observed a significant decrease in IgE-allergen complex binding to B cells with increasing quartiles of both rat-specific IgG and IgG4 antibodies (p<0.001). IgE-allergen complex binding to B cells was lower in workers with high allergen exposure, and significantly so (p=0.033) in the subgroup with highest exposures but no work-related chest symptoms. CONCLUSIONS: These findings demonstrate a functional role for rat-specific IgG/G4 antibodies in laboratory animal workers, similar to that observed in patients treated with high dose immunotherapy who become clinically tolerant, suggesting a potential explanation for the attenuation of risk at highest allergen exposures.

The psychological impact of providing women with risk information for pre-eclampsia: a qualitative study.

OBJECTIVE: a new first-trimester universal antenatal screening test for pre-eclampsia was introduced into two UK hospitals. The aim of this study was to investigate the potential psychological benefits, harms and acceptability of providing pregnant women with formal risk information for pre-eclampsia. DESIGN: cross-sectional interview study. Women were interviewed using a theoretically informed semi-structured schedule and transcripts were analysed thematically using Framework Analysis. SETTING AND PARTICIPANTS: primigravid women receiving antenatal care at a central London National Health Service Foundation Trust found either high-risk or low-risk for pre-eclampsia. FINDINGS: 15 primigravid women who received high risk (n=10) or low risk (n=5) results of a 12-week pre-eclampsia screening test were interviewed. Two types of coping typologies were evident from the data. The first were 'danger managers' who had an internal sense of control, were focused on the risk that pre-eclampsia presented to them and exhibited information seeking, positive behaviour changes, and cognitive reappraisal coping mechanisms. The second were 'fear managers' who had an external sense of control, were focused on the risk that pre-eclampsia presented to the fetus, and exhibited avoidance coping mechanisms. In addition to these typologies, three universal themes of 'medicalising the pregnancy', 'embracing technology' and 'acceptability' emerged from the data. KEY CONCLUSIONS: there are potential positive and negative unintended consequences following a first-trimester screening test for pre-eclampsia. A positive consequence could be self-instigated behaviour change, whereas a negative consequence could be reduced self-monitoring of fetal movements as the pregnancy develops. IMPLICATIONS FOR PRACTICE: this study indicates that women with an increased risk of pre-eclampsia would be willing to engage in efforts to reduce their risk of pre-eclampsia, and there is a potential to use this screening test as a basis for improving health more broadly.

PINP as a biological response marker during teriparatide treatment for osteoporosis.

Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis.

The effects of lebrikizumab in patients with mild asthma following whole lung allergen challenge.

BACKGROUND: Interleukin 13 (IL13) is a T-helper type 2 (Th2) cytokine associated with inflammation and pathology in allergic diseases such as bronchial asthma. We have shown that treatment with lebrikizumab, an anti-IL13 monoclonal antibody, significantly improves prebronchodilator forced expiratory volume in 1 s (FEV(1)) in a subset of subjects with uncontrolled asthma. OBJECTIVE: To evaluate efficacy and safety of lebrikizumab in subjects with mild asthma who underwent bronchial allergen challenge. METHODS: Twenty-nine subjects were randomized 1 : 1-5 mg/kg lebrikizumab (n = 13) or placebo (n = 16) administered subcutaneously every 4 weeks over 12 weeks, a total of four doses. Primary efficacy outcome was late asthmatic response (LAR) at Week 13, defined as area under the curve of FEV1 measured 2-8 h following inhaled allergen challenge. Serum biomarkers were measured to verify IL13 pathway inhibition and identify patients with an increased response to lebrikizumab. RESULTS: At Week 13, the LAR in lebrikizumab subjects was reduced by 48% compared with placebo subjects, although this was not statistically significant (95% confidence interval, -19%, 90%). Exploratory analysis indicated that lebrikizumab-treated subjects with elevated baseline levels of peripheral blood eosinophils, serum IgE, or periostin exhibited a greater reduction in LAR compared with subjects with lower baseline levels of these biomarkers. Lebrikizumab exerted systemic effects on markers of Th2 inflammation, reducing serum immunoglobulin E (IgE), chemokine ligands 13 and 17 by approximately 25% (P < 0.01). Lebrikizumab was well tolerated. CONCLUSION AND CLINICAL RELEVANCE: Lebrikizumab reduced the LAR in subjects with mild asthma. Clinical trial number NCT00781443.

Association of maternal anti-HLA class II antibodies with protection from allergy in offspring.

BACKGROUND: Recent studies have suggested that the birth order effect in allergy may be established during the prenatal period and that the protective effect may originate in the mother. HLA class II disparity between mother and foetus has been associated with significantly increased Th1 production. In this study, we investigated whether production of HLA antibodies 4 years after pregnancy with index child is associated with allergic outcomes in offspring at 8 years. METHODS: Anti-HLA class I and II antibodies were measured in maternal serum (n = 284) and levels correlated to numbers of pregnancies and birth order, and allergic outcomes in offspring at 8 years of age. RESULTS: Maternal anti-HLA class I and II antibodies were significantly higher when birth order, and the number of pregnancies were larger. Anti-HLA class II, but not class I antibodies were associated with significantly less atopy and seasonal rhinitis in the offspring at age 8 years. Mothers with nonatopic (but not atopic) offspring had a significant increase in anti-HLA class I and II antibodies with birth order. CONCLUSION: This study suggests that the 'birth order' effect in children may be due to parity-related changes in the maternal immune response to foetal antigens. We have observed for the first time an association between maternal anti-HLA class II antibodies and protection from allergy in the offspring. Further work is required to determine immunologically how HLA disparity between mother and father can protect against allergy.

Characterization of infectious bursal disease viruses isolated in 2007 from Delmarva commercial broiler chickens.

A study was performed in 2007 to isolate and characterize infectious bursal disease viruses (IBDVs) in commercial broilers grown in the Delmarva (DMV) Peninsula region of the United States. Bursae of Fabricius were collected weekly from 1 to 4 wk of age from broilers on 10 farms with a history of poor performance. Microscopic pathology was used to determine the infectious bursal disease (IBD) status of the broilers. Bursae from 1- and 2-wk-old broilers did not show IBD microscopic lesions. Moreover, broilers on 1 of the 10 farms were IBD lesion free at 3 and 4 wk of age. However, 3 of 9 and 9 of 9 farms yielded broilers with IBD-affected bursae from 3- and 4-wk-old commercial broilers, respectively. Ten IBDV isolates were recovered from 3 of 3 lesion-positive bursal pools at 3 wk of age and 7 of 9 lesion-positive bursal pools at 4 wk of age. Analysis of the viral protein (VP) 2 genes identified all isolates as serotype 1 Delaware (Del) variant viruses. Five field isolates, each representing different molecular clades of the Delaware variant viruses, were selected for further study. Experimental infection of specific-pathogen-free white leghorn chickens with isolates DMV/4813/07, DMV/4947/07, DMV/4955/07, DMV/5038/07, and DMV/5041/07 produced gross and microscopic pathology of the bursa consistent with Delaware variant infection. Monoclonal antibody testing showed DMV/4813/07, DMV/4947/07, DMV/ 4955/07, and DMV/5041/07 to be similar to previous recognized variant viruses. However, DMV/5038/07 was found to be unreactive with the monoclonal antibodies that typically recognize reference strains STC, Del E, GLS, RS593, and AL2. In a challenge of immunity study, 10-day-old progeny from breeders immunized with a commercially available inactivated IBDV vaccine containing the Del E and classic strains were protected to a lesser degree against isolate DMV/5038/07 compared to Del E challenge based on microscopic lesion scores (P < 0.01) of the bursa. This result suggests the virus is antigenically different from the Del E strain contained in the vaccine. Collectively, the monoclonal antibody and progeny challenge of immunity findings suggest DMV/5038/07 is antigenically different from the Del E strain contained in the vaccine.

Identification of a novel prostate cancer susceptibility variant in the KLK3 gene transcript.

Genome-wide association studies (GWAS) have identified more than 30 prostate cancer (PrCa) susceptibility loci. One of these (rs2735839) is located close to a plausible candidate susceptibility gene, KLK3, which encodes prostate-specific antigen (PSA). PSA is widely used as a biomarker for PrCa detection and disease monitoring. To refine the association between PrCa and variants in this region, we used genotyping data from a two-stage GWAS using samples from the UK and Australia, and the Cancer Genetic Markers of Susceptibility (CGEMS) study. Genotypes were imputed for 197 and 312 single nucleotide polymorphisms (SNPs) from HapMap2 and the 1000 Genome Project, respectively. The most significant association with PrCa was with a previously unidentified SNP, rs17632542 (combined P = 3.9 × 10(-22)). This association was confirmed by direct genotyping in three stages of the UK/Australian GWAS, involving 10,405 cases and 10,681 controls (combined P = 1.9 × 10(-34)). rs17632542 is also shown to be associated with PSA levels and it is a non-synonymous coding SNP (Ile179Thr) in KLK3. Using molecular dynamic simulation, we showed evidence that this variant has the potential to introduce alterations in the protein or affect RNA splicing. We propose that rs17632542 may directly influence PrCa risk.

Temporal changes in UK birth order and the prevalence of atopy.

BACKGROUND: Many studies have reported an inverse association between birth order and the risk of respiratory allergic disease. In recent decades, the prevalence of atopy has increased alongside reductions in fertility rates. AIMS OF THE STUDY: To quantitate how much of the increased prevalence of atopy, measured by skin prick test or specific IgE, can be attributed to temporal changes in family size in the United Kingdom. METHODS: Through a systematic literature review (MEDLINE, 1965-2009), five studies of UK populations were identified and their data were included in the calculation of a summary odds ratio for the risk of atopy for each birth order. Information on changes in UK family sizes between 1960 and 2001 was obtained from Eurostat. On this basis, expected increases in the prevalence of atopy were calculated by weighting the proportion in each birth order category for 1960 and 2001 by the summary odds ratio for that category and then calculating the relative risk of atopy in 2001 compared with 1960. RESULTS: The pooled summary odds ratios for atopy were 0.90, 0.69 and 0.69 for those born second, third and fourth (or higher), respectively. The expected relative increase in the prevalence of atopy resulting from a change in family size between 1960 and 2001 was 3%. CONCLUSIONS: Despite the strong associations between birth order and atopy, reductions in family size in the last 40 years account for little of the increase in atopy.

Cryptogenic fibrosing alveolitis and lung cancer: the BTS study.

BACKGROUND: The risk of lung cancer is often reported to be increased for patients with cryptogenic fibrosing alveolitis (CFA). METHODS: Vital status was sought for all 588 members of the British Thoracic Society (BTS) cryptogenic fibrosing alveolitis (CFA) study 11 years after entry to the cohort. Observed deaths due to lung cancer were compared with expected deaths using age-, sex- and period-adjusted national rates. The roles of reported asbestos exposure and smoking were also investigated. RESULTS: 488 cohort members (83%) had died; 46 (9%) were certified to lung cancer (ICD9 162). The standardised mortality ratio (SMR) was 7.4 (95% CI 5.4 to 9.9). Stratified analysis showed increased lung cancer mortality among younger subjects, men and ever smokers. Using an independent expert panel, 25 cohort members (4%) were considered to have at least moderate exposure to asbestos; the risk of lung cancer was increased for these subjects (SMR 13.1 (95% CI 3.6 to 33.6)) vs 7.2 (95% CI 5.2 to 9.7) for those with less or no asbestos exposure). Ever smoking was reported by 448 (73%) of the cohort and was considerably higher in men than in women (92% vs 49%; p<0.001). Most persons who died from lung cancer were male (87%), and all but two (96%) had ever smoked. Ever smokers presented at a younger age (mean 67 vs 70 years; p<0.001) and with less breathlessness (12% smokers reported no breathlessness vs 5% never smokers; p = 0.02). CONCLUSIONS: These findings confirm an association between CFA and lung cancer although this relationship may not be causal. The high rate of smoking and evidence that smokers present for medical attention earlier than non-smokers suggest that smoking could be confounding this association.

Differential gene expression during compensatory sprouting of dendrites in the auditory system of the cricket Gryllus bimaculatus.

Neurones that lose their presynaptic partners because of injury usually retract or die. However, when the auditory interneurones of the cricket Gryllus bimaculatus are denervated, dendrites respond by growing across the midline and forming novel synapses with the opposite auditory afferents. Suppression subtractive hybridization was used to detect transcriptional changes 3 days after denervation. This is a stage at which we demonstrate robust compensatory dendritic sprouting. Whereas 49 unique candidates were down-regulated, no sufficiently up-regulated candidates were identified at this time point. Several candidates identified in this study are known to influence the translation and degradation of proteins in other systems. The potential role of these factors in the compensatory sprouting of cricket auditory interneurones in response to denervation is discussed.

Specific cognitive deficits in a group at genetic high risk of schizophrenia.

BACKGROUND: Neuropsychological deficits in schizophrenia patients and their relatives have been thought to represent possible genetic vulnerability markers or endophenotypes of the disorder. The present study describes results from the Edinburgh High Risk Study of computerized testing using the Cambridge Neuropsychological Test Automated Battery (CANTAB) on a group at genetic high risk (HR) of schizophrenia and a control group. METHOD: A total of 97 HR and 25 control participants were assessed on three tests from the CANTAB - spatial span, spatial working memory, and Stockings of Cambridge. Analyses of covariance were used to compare the HR and control groups on the main outcome measures whilst controlling for intelligence quotient (IQ). Subsequent analysis examined the effects of the presence of symptoms on group differences. RESULTS: HR participants had significantly reduced spatial memory capacity [F(1, 118)=4.06, p=0.046] and significantly reduced planning processing speed [F(1, 116)=4.16, p=0.044] compared with controls even after controlling for general intelligence (IQ). Although HR individuals made more errors and showed poorer problem-solving and strategy performance compared with controls, these differences were not significant after controlling for IQ. Subsequent analysis indicated that the presence or absence of psychotic symptoms in the HR group did not influence these specific cognitive deficits. CONCLUSIONS: Spatial memory capacity and planning processing speed may represent cognitive endophenotypes characterising the genetic predisposition to schizophrenia in this HR group.

Lung fiber burden in the Nottingham gas mask cohort.

A cohort of 1,154 employees, mainly women, who had worked 1940-1945 on the manufacture of military gas masks using filter pads containing 20% crocidolite, was traced through 2003, by which time 65 were known to have died from mesothelioma. The last known death with mesothelioma was in 1994, whereas a further 5 cases would have been expected in those with known duration of exposure. Lung tissue samples, from 50 deaths from mesothelioma and 20 other causes, had been analyzed for mineral fiber content. For ten of the mesothelioma cases data on fiber size were collected. Crocidolite fiber concentrations were analyzed in relation to exposure by time and duration. Fiber concentrations overall fell fairly steadily by decade of death, and increased with length of exposure up to 36 months and then fell sharply. The annual rate of elimination estimated by regression was 7.5% corresponding to a half life of 9.2 years. The proportion of fibers longer than 6 mum increased over time implying that the shorter fibers were eliminated more rapidly than the longer ones. The decline in concentrations with time confirms the hypothesis that crocidolite and, by inference, other amphibole fibers are slowly removed from the lung, but since the longer more carcinogenic fibers were cleared more slowly it is unclear to what extent this clearance explains the slowing down of the increase in mesothelioma mortality from about 40 years from the most recent exposure. The exact biostatistical models which most closely conform with the data remain open to question.