Phacoemulsification with posterior chamber intraocular lens versus extracapsular cataract extraction (ECCE) with posterior chamber intraocular lens for age-related cataract.

BACKGROUND: Age-related cataract is one of the leading causes of blindness worldwide. Therefore, it is important to establish the most effective surgical technique for cataract surgery. OBJECTIVES: The aim of this review is to examine the effects of two types of cataract surgery for age-related cataract: phacoemulsification and extracapsular cataract extraction (ECCE). SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to May 2013), EMBASE (January 1980 to May 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to May 2013), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1970 to May 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 May 2013. SELECTION CRITERIA: We included randomised controlled trials of phacoemulsification compared to ECCE for age-related cataract. DATA COLLECTION AND ANALYSIS: Two authors independently selected and assessed all studies. We defined two primary outcomes: 'good functional vision' (presenting visual acuity of 6/12 or better) and 'poor visual outcome' (best corrected visual acuity of less than 6/60) at three and 12 months after surgery. We also collected data on intra and postoperative complications, and the cost of the procedures. MAIN RESULTS: We included 11 trials in this review with a total of 1228 participants, ranging from age 45 to 94. The studies were generally at unclear risk of bias due to poorly reported trial methods. No study reported presenting visual acuity, so we report both uncorrected (UCVA) and best corrected visual acuity (BCVA). Studies varied in visual acuity assessment methods and time frames at which outcomes were reported. Participants in the phacoemulsification group were more likely to achieve UCVA of 6/12 or more at three months (risk ratio (RR) 1.81, 95% confidence interval (CI) 1.36 to 2.41, two studies, 492 participants) and one year (RR 1.99, 95% CI 1.45 to 2.73, one study, 439 participants). People in the phacoemulsification group were also more likely to achieve BCVA of 6/12 or more at three months (RR 1.12, 95% CI 1.03 to 1.22, four studies, 645 participants) and one year (RR 1.06, 95% CI 0.99 to 1.14, one study, 439 participants), but the difference between the two groups was smaller. No trials reported BCVA less than 6/60 but three trials reported BCVA worse than 6/9 and 6/18: there were fewer events of this outcome in the phacoemulsification group than the ECCE group at both the three-month (RR 0.33, 95% CI 0.20 to 0.55, three studies, 604 participants) and 12-month time points (RR 0.62, 95% CI 0.36 to 1.05, one study, 439 participants). Three trials reported posterior capsule rupture: this occurred more commonly in the ECCE group than the phacoemulsification group but small numbers of events mean the true effect is uncertain (Peto odds ratio (OR) 0.56, 95% CI 0.26 to 1.22, three studies, 688 participants). Iris prolapse, cystoid macular oedema and posterior capsular opacification were also higher in the ECCE group than the phacoemulsification group. Phacoemulsification surgical costs were higher than ECCE in two studies. A third study reported similar costs for phacoemulsification and ECCE up to six weeks postoperatively, but following this time point ECCE incurred additional costs due to additional visits, spectacles and laser treatment to achieve a similar outcome. AUTHORS' CONCLUSIONS: Removing cataract by phacoemulsification may result in a better visual acuity compared to ECCE, with a lower complication rate. The review is currently underpowered to detect differences for rarer outcomes, including poor visual outcome. The lower cost of ECCE may justify its use in a patient population where high-volume surgery is a priority, however, there are a lack of data comparing phacoemulsification and ECCE in lower-income settings

Multifocal versus monofocal intraocular lenses after cataract extraction.

BACKGROUND: Good unaided distance visual acuity (VA) is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: To assess the visual effects of multifocal IOLs in comparison with the current standard treatment of monofocal lens implantation. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2016), Embase (January 1980 to June 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016. SELECTION CRITERIA: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. We also considered trials comparing multifocal IOLs with "monovision" whereby one eye is corrected for distance vision and one eye corrected for near vision. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We assessed the 'certainty' of the evidence using GRADE. MAIN RESULTS: We found 20 eligible trials that enrolled 2230 people with data available on 2061 people (3194 eyes). These trials were conducted in Europe (13), China (three), USA (one), Middle East (one), India (one) and one multicentre study in Europe and the USA. Most of these trials compared multifocal with monofocal lenses; two trials compared multifocal lenses with monovision. There was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask participants and outcome assessors. It was also difficult to assess the role of reporting bias.There was moderate-certainty evidence that the distance acuity achieved with multifocal lenses was not different to that achieved with monofocal lenses (unaided VA worse than 6/6: pooled RR 0.96, 95% confidence interval (CI) 0.89 to 1.03; eyes = 682; studies = 8). People receiving multifocal lenses may achieve better near vision (RR for unaided near VA worse than J3/J4 was 0.20, 95% CI 0.07 to 0.58; eyes = 782; studies = 8). We judged this to be low-certainty evidence because of risk of bias in the included studies and high heterogeneity (I2 = 93%) although all included studies favoured multifocal lenses with respect to this outcome.People receiving multifocal lenses may be less spectacle dependent (RR 0.63, 95% CI 0.55 to 0.73; eyes = 1000; studies = 10). We judged this to be low-certainty evidence because of risk of bias and evidence of publication bias (skewed funnel plot). There was also high heterogeneity (I2 = 67%) but all studies favoured multifocal lenses. We did not additionally downgrade for this.Adverse subjective visual phenomena were more prevalent and more troublesome in participants with a multifocal IOL compared with monofocals (RR for glare 1.41, 95% CI 1.03 to 1.93; eyes = 544; studies = 7, low-certainty evidence and RR for haloes 3.58, 95% CI 1.99 to 6.46; eyes = 662; studies = 7; moderate-certainty evidence).Two studies compared multifocal lenses with monovision. There was no evidence for any important differences in distance VA between the groups (mean difference (MD) 0.02 logMAR, 95% CI -0.02 to 0.06; eyes = 186; studies = 1), unaided intermediate VA (MD 0.07 logMAR, 95% CI 0.04 to 0.10; eyes = 181; studies = 1) and unaided near VA (MD -0.04, 95% CI -0.08 to 0.00; eyes = 186; studies = 1) compared with people receiving monovision. People receiving multifocal lenses were less likely to be spectacle dependent (RR 0.40, 95% CI 0.30 to 0.53; eyes = 262; studies = 2) but more likely to report problems with glare (RR 1.41, 95% CI 1.14 to 1.73; eyes = 187; studies = 1) compared with people receiving monovision. In one study, the investigators noted that more people in the multifocal group underwent IOL exchange in the first year after surgery (6 participants with multifocal vs 0 participants with monovision). AUTHORS' CONCLUSIONS: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs although there is uncertainty as to the size of the effect. Whether that improvement outweighs the adverse effects of multifocal IOLs, such as glare and haloes, will vary between people. Motivation to achieve spectacle independence is likely to be the deciding factor

CERKL-associated retinal dystrophy: Genetics, Phenotype and Natural History

PURPOSE: To analyze the clinical characteristics, natural history, and genetics of CERKL-associated retinal dystrophy in the largest series to date. DESIGN: Multicenter retrospective cohort study. SUBJECTS: 47 patients (37 families) with likely disease-causing CERKL variants METHODS: Review of clinical notes, ophthalmic images, and molecular diagnosis from two international centres. MAIN OUTCOME MEASURES: Visual function, retinal imaging and characteristics were evaluated and correlated. RESULTS: The mean age at the first visit was 29.6 + 13.9 years and the mean follow-up time was 9.1 + 7.4 years. The most frequent initial symptom was central vision loss (40%) and the most common retinal feature was well-demarcated areas of macular atrophy (57%). Seventy percent of the participants had double-null genotypes and 64% had electrophysiological assessment. Amongst the latter, 53% showed similar severity of rod and cone dysfunction, 27% revealed a rod-cone, 10% a cone-rod, and 10% a macular dystrophy dysfunction pattern. Patients without double-null genotypes tended to have fewer pigment deposits and included a higher proportion of older patients with a relatively mild electrophysiological phenotype. Longitudinal analysis showed that over half of the cohort lost 15 ETDRS letters or more in at least one eye during the first 5 years of follow up. CONCLUSIONS: The phenotype of CERKL-retinal dystrophy is broad, encompassing isolated macular disease to severe retina-wide involvement, with a range of functional phenotypes, generally not fitting in the rod-cone/cone-rod dichotomy. Disease onset is often earlier, with more severe retinal degenerative changes and photoreceptor dysfunction, in nullizygous cases

Male synthetic sling versus artificial urinary sphincter trial for men with urodynamic stress incontinence after prostate surgery (MASTER): Study protocol for a randomised controlled trial

© 2018 The Author(s). Background: Stress urinary incontinence (SUI) is a frequent adverse effect for men undergoing prostate surgery. A large proportion (around 8% after radical prostatectomy and 2% after transurethral resection of prostate (TURP)) are left with severe disabling incontinence which adversely effects their quality of life and many are reliant on containment measures such as pads (27% and 6% respectively). Surgery is currently the only option for active management of the problem. The overwhelming majority of surgeries for persistent bothersome SUI involve artificial urinary sphincter (AUS) insertion. However, this is expensive, and necessitates manipulation of a pump to enable voiding. More recently, an alternative to AUS has been developed - a synthetic sling for men which elevates the urethra, thus treating SUI. This is thought, by some, to be less invasive, more acceptable and less expensive than AUS but clear evidence for this is lacking. The MASTER trial aims to determine whether the male synthetic sling is non-inferior to implantation of the AUS for men who have SUI after prostate surgery (for cancer or benign disease), judged primarily on clinical effectiveness but also considering relative harms and cost-effectiveness. Methods/design: Men with urodynamic stress incontinence (USI) after prostate surgery, for whom surgery is judged appropriate, are the target population. We aim to recruit men from secondary care urological centres in the UK NHS who carry out surgery for post-prostatectomy incontinence. Outcomes will be assessed by participant-completed questionnaires and 3-day urinary bladder diaries at baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline as an objective assessment of urine loss. Clinical data will be completed at the time of surgery to provide details of the operative procedures, complications and resource use in hospital. At 12 months, men will also have a clinical review to evaluate the results of surgery (including another 24-h pad test) and to identify problems or need for further treatment. Discussion: A robust examination of the comparative effectiveness of the male synthetic sling will provide high-quality evidence to determine whether or not it should be adopted widely in the NHS

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein–protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein–protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation

Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding

Objectives Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations. Design We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity. Results Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients. Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour

A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research

The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science