Homozygous in-frame deletion in CATSPERE in a man producing spermatozoa with loss of CatSper function and compromised fertilizing capacity

STUDY QUESTIONDoes a man (patient 1) with a previously described deficiency in principle cation channel of sperm (CatSper) function have a mutation in the CatSper-epsilon (CATSPERE) and/or CatSper-zeta (CATSPERZ) gene?SUMMARY ANSWERPatient 1 has a homozygous in-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, rs761237686) of CATSPERE.WHAT IS KNOWN ALREADYCatSper is the principal calcium channel of mammalian spermatozoa. Spermatozoa from patient 1 had a specific loss of CatSper function and were unable to fertilize at IVF. Loss of CatSper function could not be attributed to genetic abnormalities in coding regions of seven CatSper subunits. Two additional subunits (CatSper-epsilon (CATPSERE) and CatSper-zeta (CATSPERZ)) were recently identified, and are now proposed to contribute to the formation of the mature channel complex.STUDY DESIGN, SIZE, DURATIONThis was a basic medical research study analysing genomic data from a single patient (patient 1) for defects in CATSPERE and CATSPERZ.PARTICIPANTS/MATERIALS, SETTING, METHODSThe original exome sequencing data for patient 1 were analysed for mutations in CATSPERE and CATSPERZ. Sanger sequencing was conducted to confirm the presence of a rare variant.MAIN RESULTS AND THE ROLE OF CHANCEPatient 1 is homozygous for an in-frame 6-bp deletion in exon 18 (c.2393_2398delCTATGG, rs761237686) of CATSPERE that is predicted to be highly deleterious.LIMITATIONS, REASONS FOR CAUTIONThe nature of the molecular deficit caused by the rs761237686 variant and whether it is exclusively responsible for the loss of CatSper function remain to be elucidated.WIDER IMPLICATIONS OF THE FINDINGSPopulation genetics are available for a significant number of predicted deleterious variants of CatSper subunits. The consequence of homozygous and compound heterozygous forms on sperm fertilization potential could be significant. Selective targeting of CatSper subunit expression maybe a feasible strategy for the development of novel contraceptives.STUDY FUNDING/COMPETING INTEREST(S)This study was funded by project grants from the MRC (MR/K013343/1 and MR/012492/1), Chief Scientist Office/NHS research Scotland. This work was also supported by NIH R01GM111802, Pew Biomedical Scholars Award 00028642 and Packer Wentz Endowment Will to P.V.L. C.L.R.B is the editor-in-chief of Molecular Human Reproduction, has received lecturing fees from Merck and Ferring, and is on the Scientific Advisory Panel for Ohana BioSciences. C.L.R.B was chair of the World Health Organization Expert Synthesis Group on Diagnosis of Male infertility (2012–2016)

Star formation in the inner galaxy: A far-infrared and radio study of two H2 regions

Far-infrared and radio continuum maps have been made of the central 6' of the inner-galaxy HII regions G30.8-0.0 (in the W43 complex) and G25.4-0.2, along with radio and molecular line measurements at selected positions. The purpose of this study is an effort to understand star formation in the molecular ring at 5 kpc in galactic radius. Measurements at several far infrared wavelengths allow the dust temperature structures and total far infrared fluxes to be determined. Comparison of the radio and infrared maps shows a close relationship between the ionized gas and the infrared-emitting material. There is evidence that parts of G30.8 are substantially affected by extinction, even at far-infrared wavelengths. Using radio recombination line and CO line data for G25.4-0.2, the distance ambiguity for this source is resolved. The large distance previously ascribed to the entire complex is found to apply to only one of the two main components. The confusion in distance determination is found to result from an extraordinary near-superposition of two bright HII regions. Using the revised distances of 4.3 kpc for G25.4SE and 12 kpc for G25.4NW, it is found that the latter, which is apparently the fainter of the two sources, is actually the more luminous. The ratio of total luminosity to ionizing luminosity is very similar to that of HII regions in the solar circle. Assuming a coeval population of ionizing stars, a normal initial mass function is indicated

Star formation in the inner galaxy: A far-infrared and radio study of two H2 regions

Far-infrared and radio continuum maps have been made of the central 6' of the inner-galaxy H II regions G30.8-0.0 (in the W43 complex) and G25.4-02., along with radio and molecular line measurements at selected positions. An effort is made to understand far infrared wavelingths allow the dust temperature structures and total far infrared fluxes to be determined. Comparison of the radio and infrared maps shows a close relationship between the ionized gas and the infrared-emitting material. There is evidence that parts of G30.8 are substantially affected by extinction, even at far-infrared wavelengths. For G25.4-0.2, the radio recombination line and CO line data permit resolution of the distance ambiguity for this source. The confusion in distance determination is found to result from an extraordinary near-superposition of two bright H II regions. Using revised distances of 4.3 kpc for G26.4SE and 12 kpc for G25.4NW, that the latter, which is apparently the fainter of the two sources, is actually the more luminous. Though it is not seen on the Palomar Sky Survey, G25.4SE is easily visible in the 9532A line of S III and is mapped in this line. The ratio of total luminosity to ionizing luminosity is very similar to that of H II regions in the solar circle. Assuming a coeval population of ionizing stars, a normal initial mass function is indicated

An evaluation of metal removal during wastewater treatment: The potential to achieve more stringent final effluent standards

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2011 Taylor & Francis.Metals are of particular importance in relation to water quality, and concern regarding the impact of these contaminants on biodiversity is being encapsulated within the latest water-related legislation such as the Water Framework Directive in Europe and criteria revisions to the Clean Water Act in the United States. This review undertakes an evaluation of the potential of 2-stage wastewater treatment consisting of primary sedimentation and biological treatment in the form of activated sludge processes, to meet more stringent discharge consents that are likely to be introduced as a consequence. The legislation, sources of metals, and mechanisms responsible for their removal are discussed, to elucidate possible pathways by which the performance of conventional processes may be optimized or enhanced. Improvements in effluent quality, achievable by reducing concentrations of suspended solids or biochemical oxygen demand, may also reduce metal concentrations although meeting possible requirements for the removal of copper my be challenging

A Simpler Machine Learning Model for Acute Kidney Injury Risk Stratification in Hospitalized Patients

Background: Hospitalization-associated acute kidney injury (AKI), affecting one-in-five inpatients, is associated with increased mortality and major adverse cardiac/kidney endpoints. Early AKI risk stratification may enable closer monitoring and prevention. Given the complexity and resource utilization of existing machine learning models, we aimed to develop a simpler prediction model. Methods: Models were trained and validated to predict risk of AKI using electronic health record (EHR) data available at 24 h of inpatient admission. Input variables included demographics, laboratory values, medications, and comorbidities. Missing values were imputed using multiple imputation by chained equations. Results: 26,410 of 209,300 (12.6%) inpatients developed AKI during admission between 13 July 2012 and 11 July 2018. The area under the receiver operating characteristic curve (AUROC) was 0.86 for Random Forest and 0.85 for LASSO. Based on Youden’s Index, a probability cutoff of \u3e0.15 provided sensitivity and specificity of 0.80 and 0.79, respectively. AKI risk could be successfully predicted in 91% patients who required dialysis. The model predicted AKI an average of 2.3 days before it developed. Conclusions: The proposed simpler machine learning model utilizing data available at 24 h of admission is promising for early AKI risk stratification. It requires external validation and evaluation of effects of risk prediction on clinician behavior and patient outcomes

Modelling the tongue-of-ionisation using CTIP with SuperDARN electric potential input: verification by radiotomography

Electric potential patterns obtained by the SuperDARN radar network are used as input to the Coupled Thermosphere-Ionosphere-Plasmasphere model, in an attempt to improve the modelling of the spatial distribution of the ionospheric plasma at high latitudes. Two case studies are considered, one under conditions of stable IMF <I>B<sub>z</sub></I> negative and the other under stable IMF <I>B<sub>z</sub></I> positive. The modelled plasma distributions are compared with sets of well-established tomographic reconstructions, which have been interpreted previously in multi-instrument studies. For IMF <I>B<sub>z</sub></I> negative both the model and observations show a tongue-of-ionisation on the nightside, with good agreement between the electron density and location of the tongue. Under <I>B<sub>z</sub></I> positive, the SuperDARN input allows the model to reproduce a spatial plasma distribution akin to that observed. In this case plasma, unable to penetrate the polar cap boundary into the polar cap, is drawn by the convective flow in a tongue-of-ionisation around the periphery of the polar cap

Public Health Response to Imported Case of Poliomyelitis, Australia, 2007

Inactivated polio vaccine was offered, and the index case-patient and household contacts were quarantined

A national audit of current cardiac device policies from radiotherapy centres across the UK

Aims: The number of patients with cardiac implantable electronic devices (permanent pacemakers and implantable cardioverter defibrillators) undergoing radiotherapy treatment is increasing. The aims of this audit were to establish current UK practice regarding the management of patients with implanted cardiac devices undergoing radiotherapy and to compare this practice with current ‘gold standard’ evidence-based guidelines. Materials and methods: All UK radiotherapy departments were contacted and asked to provide their current cardiac implantable electronic device policy or to indicate if there was no current policy. A proforma was created to analyse these polices and to compare with current best practice. Results: In total, 47/67 (70%) radiotherapy departments responded and 45 departmental policies were submitted; 31/45 (69%) policies defined the radiotherapy tolerance dose to permanent pacemakers and 14/45 (31%) defined the monitoring procedure for patients in line with current best practice. Only 5/45 (11%) policies defined the radiotherapy tolerance dose to implantable cardioverter defibrillators and 12/45 (27%) defined the monitoring procedure in line with current best practice. Conclusion: Most UK cardiac device policies do not reflect current best evidence. Policies are based on research carried out in 1994 by the American Association of Physicists in Medicine. This evidence does not account for advances in cardiac implantable electronic device technology. Further research is urgently needed to establish the effect of radiotherapy on these devices

PTPN22 R620W minor allele is a genetic risk factor for giant cell arteritis

Published online 7 April 2016.Giant cell arteritis (GCA) is one of the commonest forms of vasculitis in the elderly, and may result in blindness and stroke. The pathogenesis of GCA is not understood, although environmental, infectious and genetic risk factors are implicated. One gene of interest is PTPN22, encoding lymphoid protein tyrosine phosphatase (Lyp), expressed exclusively in immune cells, which is proposed to be an 'archetypal non-HLA autoimmunity gene'. The minor allele of a functional PTPN22 single nucleotide polymorphism (rs2476601, R620W), which disrupts an interaction motif in the protein, was originally reported to be associated with biopsy-proven GCA in Spanish patients, with supporting data from three replicate Northern European studies. Recently, this observation was extended with additional patients and controls, and studies encompassing European, Scandinavian, UK and American patients. The aim of our study was to determine the association between PTPN22 rs2476601 (R620W) and biopsy-proven GCA in an Australian case cohort.Susan Lester, Alex W Hewitt, Carlee D Ruediger, Linda Bradbury, Elisabeth De Smit, Michael D Wiese, Rachel Black, Andrew Harrison, Graeme Jones, Geoffrey O Littlejohn, Tony R Merriman, Bain Shenstone, Malcolm D Smith, Maureen Rischmueller, Matthew A Brown, Catherine L Hil