Common genetic variants with fetal effects on birth weight are enriched for proximity to genes implicated in rare developmental disorders

This is the final version. Available on open access from Oxford University Press via the DOI in this recordData availability: This study makes use of data generated by the DECIPHER community. A full list of centres who contributed to the generation of the data is available from https://decipher.sanger.ac.uk and via email from [email protected] weight is an important factor in newborn survival; both low and high birth weights are associated with adverse later-life health outcomes. Genome-wide association studies (GWAS) have identified 190 loci associated with maternal or fetal effects on birth weight. Knowledge of underlying causal genes is crucial to understand how these loci influence birth weight, and links between infant and adult morbidity. Numerous monogenic developmental syndromes are associated with birth weights at the extreme ends of the distribution. Genes implicated in those syndromes may provide valuable information to prioritise candidate genes at GWAS loci. We examined the proximity of genes implicated in developmental disorders to birth weight GWAS loci, using simulations to test whether they fall disproportionately close to the GWAS loci. We found birth weight GWAS single nucleotide polymorphisms (SNPs) fall closer to such genes than expected, both when the developmental disorder gene is the nearest gene to the birth weight SNP and also examining all genes within 258kb of the SNP. This enrichment was driven by genes causing monogenic developmental disorders with dominant modes of inheritance. We found examples of SNPs in the intron of one gene marking plausible effects via different nearby genes, highlighting the closest gene to the SNP not necessarily being the functionally relevant gene. This is the first application of this approach to birth weight, which has helped identify GWAS loci likely to have direct fetal effects on birth weight which could not previously be classified as fetal or maternal due to insufficient statistical power.Wellcome TrustRoyal Societ

Vesicocutaneous Fistula Presenting Groin Abscess and Chronic Osteomyelitis in Pubic Bone

The authors report a case of bladder fistula associated with a medial thigh cutaneous fistula and chronic osteomyelitis of the pubic bone 11 years after surgery for a pelvic bone fracture and bladder rupture. In the presenting case, despite the clinical suspicion, none of the diagnostic tools demonstrated the bladder fistula preoperatively. This case suggests that bladder repair should be prepared, even if the bladder fistula cannot be confirmed by imaging studies because the amount of urine leakage can be minimal or the fistula can close spontaneously

Intraoperative Adjustment in Strabismus Surgery under Topical Anesthesia

We evaluated the one-stage intraoperative adjustment strabismus surgery with adjustable suture under topical anesthesia. Medical records of the patients who had intraoperative adjustment surgery under topical anesthesia for horizontal or vertical strabismus in our hospital from March 1997 to March 2003 with follow-up of 6 months were analyzed retrospectively. Of the 71 patients, 48 patients had exotropia, 16 had esotropia, and 7 had hyper- or hypotropia. The overall success rates were 85.9% at 1 week, 83% at 1 month, 78.9% at 3 months, and 76.1% at 6 months after surgery. The procedure was not stopped in any patients, and no serious intra-operative or postoperative complications were noted. Intraoperative adjustment strabismus surgery under topical anesthesia is a simple, well-tolerated and effective procedure

Galaxy and Mass Assembly (GAMA): Improved emission lines measurements in four representative samples at 0.07 < z < 0.3

© ESO, 2016. This paper presents a new catalog of emission lines based on the GAMA II data for galaxies between 0.07 9.4 at z ∼ 0.1 and log M∗ > 10.6 at z ∼ 0.30. We have developed a dedicated code called MARVIN that automates the main steps of the data analysis, but imposes visual individual quality control of each measurement. We use this catalog to investigate how the sample selection influences the shape of the stellar mass - metallicity relation. We find that commonly used selection criteria on line detections and by AGN rejection could affect the shape and dispersion of the high-mass end of the M - Z relation. For log M∗ > 10.6, common selection criteria reject about 65% of the emission-line galaxies. We also find that the relation does not evolve significantly from z = 0.07 to z = 0.34 in the range of stellar mass for which the samples are representative (log M∗ > 10.6). For lower stellar masses (log M∗ < 10.2) we are able to show that the observed 0.15 dex metallicity decrease in the same redshift range is a consequence of a color bias arising from selecting targets in the r-band. We highlight that this color selection bias affects all samples selected in r-band (e.g., GAMA and SDSS), even those drawn from volume-limited samples. Previously reported evolution of the M - Z relation at various redshifts may need to be revised to evaluate the effect of this selection bias

Coronary artery bypass grafting and sensorineural hearing loss, a cohort study

BACKGROUND: Sudden sensorineural hearing loss is routinely encountered by the otologist. The etiology is varied and often identifiable. One of the relatively less frequent causes is surgery. Apart from being an established entity with otological surgeries, sensorineural hearing loss has also been known to occur after non-otological procedures under general anesthesia. Commonest amongst these procedures is cardiopulmonary bypass, an association that has long been recognized. However, despite the proposition of diverse hypotheses in the past, the pathophysiology remains unclear. METHODS: The study is a prospective matched cohort study that will be carried out in Aga Khan University Hospital, Karachi, Pakistan. Participants among exposed would include all those patients who would be undergoing coronary artery bypass surgery in the hospital who fall under the criteria for inclusion. Unexposed group would comprise of patients undergoing a non-bypass procedure of similar duration under the same type of anesthesia who meet the selection criteria. Both these groups will undergo audiometric testing at our hospital on three different occasions during the course of this study. Initially before the procedure to test the baseline hearing capacity; then one week after the procedure to assess any changes in hearing ability following the surgery; and finally a third audiogram at six weeks follow-up to assess further changes in any hearing deficits noted during the second phase of testing. Certain variables including the subjects' demographics and those concerning the procedure itself will be noted and used later for risk factors analysis. A detailed past medical and surgical history will also be obtained. Data analysis would include calculation of relative risk and significance of the results, by running the chi-square test. Other statistical tests like Fisher exact test may then be employed to facilitate data interpretation. Continuous scale may then be employed and multivariate linear regression used. DISCUSSION: This study is planned to obtain a better understanding of the correlation between sudden sensorineural hearing loss and cardiopulmonary bypass. Being the first major cohort trial in this line of investigation, the project is designed to identify the existence of any significant relationship between cardiopulmonary bypass and sensorineural hearing deficit

Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.

Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment

Compressive effects in melting of palladium thin films studied by ultrafast x-ray diffraction

With the advent of x-ray free electron lasers (XFELs), ultrafast laser excitation leading to nonequilibrium states has become an important way to investigate thermal processes. Here, we use ultrafast x-ray diffraction in an XFEL pump-probe experiment to examine the lattice dynamics of 300 nm polycrystalline palladium (Pd) thin films. In our experiment, at higher laser fluence levels, we directly observe a compression effect launched from the surface skin layer heated by the optical pulse which propagates across the film over the first tens of picoseconds. After that, a lattice expansion becomes dominant, followed by a quasi-steady state lasting into the nanosecond timescale. For the lowest fluence, the compression component is not detected, indicating that the dynamics is highly dependent on the laser power. Our results shed light on the dynamics behind ultrafast processes in metallic Pd, and they can be extended to different crystalline structures

Galaxy and Mass Assembly: luminosity and stellar mass functions in GAMA groups

How do galaxy properties (such as stellar mass, luminosity, star formation rate, and morphology) and their evolution depend on the mass of their host dark matter halo? Using the Galaxy and Mass Assembly (GAMA) group catalogue, we address this question by exploring the dependence on host halo mass of the luminosity function (LF) and stellar mass function (SMF) for grouped galaxies subdivided by colour, morphology and central/satellite. We find that spheroidal galaxies in particular dominate the bright and massive ends of the LF and SMF, respectively. More massive haloes host more massive and more luminous central galaxies. The satellite LF and SMF respectively show a systematic brightening of characteristic magnitude, and increase in characteristic mass, with increasing halo mass. In contrast to some previous results, the faint-end and low-mass slopes show little systematic dependence on halo mass. Semi-analytic models and simulations show similar or enhanced dependence of central mass and luminosity on halo mass. Faint and low-mass simulated satellite galaxies are remarkably independent of halo mass, but the most massive satellites are more common in more massive groups. In the first investigation of low-redshift LF and SMF evolution in group environments, we find that the red/blue ratio of galaxies in groups has increased since redshift $z \approx 0.3$ relative to the field population. This observation strongly suggests that quenching of star formation in galaxies as they are accreted into galaxy groups is a significant and ongoing process

New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: odontogenic and maxillofacial bone tumours.

The latest (4th) edition of the World Health Organization Classification of Head and Neck tumours has recently been published with a number of significant changes across all tumour sites. In particular, there has been a major attempt to simplify classifications and to use defining criteria which can be used globally in all situations, avoiding wherever possible the use of complex molecular techniques which may not be affordable or widely available. This review summarises the changes in Chapter 8: Odontogenic and maxillofacial bone lesions. The most significant change is the re-introduction of the classification of the odontogenic cysts, restoring this books status as the only text which classifies and defines the full range of lesions of the odontogenic tissues. The consensus group considered carefully the terminology of lesions and were concerned to ensure that the names used properly reflected the best evidence regarding the true nature of specific entities. For this reason, this new edition restores the odontogenic keratocyst and calcifying odontogenic cyst to the classification of odontogenic cysts and rejects the previous terminology (keratocystic odontogenic tumour and calcifying cystic odontogenic tumour) which were intended to suggest that they are true neoplasms. New entities which have been introduced include the sclerosing odontogenic carcinoma and primordial odontogenic tumour. In addition, some previously poorly defined lesions have been removed, including the ameloblastic fibrodentinoma, ameloblastic fibro-odontoma, which are probably developing odontomas, and the odontoameloblastoma, which is not regarded as an entity. Finally, the terminology "cemento" has been restored to cemento-ossifying fibroma and cemento-osseous dysplasias, to properly reflect that they are of odontogenic origin and are found in the tooth-bearing areas of the jaws

Genetic variation in TIMP1 but not MMPs predict excess FEV1 decline in two general population-based cohorts

BACKGROUND: An imbalance in matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) contributes to chronic obstructive pulmonary disease (COPD) development. Longitudinal studies investigating Single Nucleotide Polymorphisms (SNPs) in MMPs and TIMPs with respect to COPD development and lung function decline in the general population are lacking. METHODS: We genotyped SNPs in MMP1 (G-1607GG), MMP2 (-1306 C/T), MMP9 (3 tagging SNPs), MMP12 (A-82G and Asn357Ser) and TIMP1 (Phe124Phe and Ile158Ile) in 1390 Caucasians with multiple FEV1 measurements from a prospective cohort study in the general population. FEV1 decline was analyzed using linear mixed effect models adjusted for confounders. Analyses of the X-chromosomal TIMP1 gene were stratified according to sex. All significant associations were repeated in an independent general population cohort (n=1152). RESULTS: MMP2 -1306 TT genotype carriers had excess FEV1 decline (-4.0 ml/yr, p=0.03) compared to wild type carriers. TIMP1 Ile158Ile predicted significant excess FEV1 decline in both males and females. TIMP1 Phe124Phe predicted significant excess FEV1 decline in males only, which was replicated (p=0.10) in the second cohort. The MMP2 and TIMP1 Ile158Ile associations were not replicated. Although power was limited, we did not find associations with COPD development. CONCLUSIONS: We for the first time show that TIMP1 Phe124Phe contributes to excess FEV1 decline in two independent prospective cohorts, albeit not quite reaching conventional statistical significance in the replication cohort. SNPs in MMPs evidently do not contribute to FEV1 decline in the general population