Results and safety profile of trainee cataract surgeons in a community setting in East Africa

Purpose: To evaluate the results and safety profile of assistant medical officer ophthalmologists (AMO-O) performing cataract surgery in the last stage of their surgical training, before their appointment to local communities. Methods: We retrospectively analyzed the records of patients who underwent cataract surgery by AMO-Os at Dar es Salaam, Comprehensive Community Based Rehabilitation for Tanzania Disability Hospital between September 2008 and June 2011. Surgical options were either extracapsular cataract extraction (ECCE) or manual small incision cataract surgery (MSICS), both with polymethylmethacrylate intraocular lens implantation. Results: Four hundred and fourteen patients were included in the study. Two hundred and twenty-five (54%) underwent ECCE and 189 had MSICS. Mean logarithm of the minimum angle of resolution (logMAR) uncorrected visual acuity (UCVA) improved from 2.4 ± 0.6 preoperatively to 1.3 ± 0.8 1 week postoperatively (t-test, P < 0.001) and to 1.1 ± 0.7 3 months postoperatively (t-test, P < 0.001). Mean logMAR best-corrected visual acuity (BCVA) was 0.7 ± 0.5 1 week postoperatively and 0.6 ± 0.5 3 months postoperatively. There was no significant difference in mean logMAR UCVA (P = 0.7) and BCVA (P = 0.7) postoperatively between ECCE and MSICS. 89.5% achieved BCVA better than 6/60 and 57.3% better than 6/18 with a follow-up of 3 months. Posterior capsule rupture and/or vitreous loss occurred in 34/414 patients (8.2%) and was more frequent (P = 0.047) in patients undergoing ECCE (10.2%) compared with MSICS (5.3%). Conclusion: AMO-O cataract surgeons at the end of their training offer significant improvement in the visual acuity of their patients. Continuous monitoring of outcomes will guide further improvements in surgical skills and minimize complications. In the era of phacoemulsification for cataract surgery, extracapsular cataract extraction (ECCE) and manual small incision cataract surgery (MSICS) are still widely held to be the techniques of choice for the developing world.[1],[2],[3],[4],[5] Both MSICS and ECCE are affordable[6] and are considered safe and effective for the treatment of cataract patients in community eye care settings. MSICS appears to provide better postoperative uncorrected visual acuity (UCVA)[1] and faster rehabilitation[7] compared with ECCE although the technique is more challenging. In Tanzania, in addition to medical doctors, there is a special cadre of health professionals, created to care for the large population, called assistant medical officers (AMOs). AMOs can specialize in ophthalmology for 2 years and become AMO ophthalmologists (AMO-O) who perform cataract surgery. AMO-O's are a subtype of nonphysician cataract surgeons previously described by Lewallen et al.[8] AMO-Os deliver high-volume cataract surgery in community eye care settings and are essential in reducing the backlog of cataract-related visual disability. AMO-Os are more likely to set up their practice and stay in rural areas than ophthalmologists tied to larger centers and in addition, their training is shorter and less expensive compared to ophthalmologists.[8],[9] Ensuring sufficient training of AMO-Os in cataract surgery is necessary to achieve good visual outcomes and maintain low rates of complications. This is particularly important in an African community setting, where follow-up may not be optimal and management of complications more challenging. In this study, we evaluate the results and safety profile of AMO-O cataract surgeons. The surgeries were supervised by trainers and performed entirely by the AMO-O in the last stage of their surgical training (6-9 months), before operating independently in their local communities. Patients with diabetes were excluded from the surgical cohort for AMO-Os

Multifrequency Photo-polarimetric WEBT Observation Campaign on the Blazar S5 0716+714: Source Microvariability and Search for Characteristic Timescales

Here we report on the results of the WEBT photo-polarimetric campaign targeting the blazar S5~0716+71, organized in March 2014 to monitor the source simultaneously in BVRI and near IR filters. The campaign resulted in an unprecedented dataset spanning $\sim 110$\,h of nearly continuous, multi-band observations, including two sets of densely sampled polarimetric data mainly in R filter. During the campaign, the source displayed pronounced variability with peak-to-peak variations of about $30\%$ and "bluer-when-brighter" spectral evolution, consisting of a day-timescale modulation with superimposed hourlong microflares characterized by $\sim 0.1$\,mag flux changes. We performed an in-depth search for quasi-periodicities in the source light curve; hints for the presence of oscillations on timescales of $\sim 3$\,h and $\sim 5$\,h do not represent highly significant departures from a pure red-noise power spectrum. We observed that, at a certain configuration of the optical polarization angle relative to the positional angle of the innermost radio jet in the source, changes in the polarization degree led the total flux variability by about 2\,h; meanwhile, when the relative configuration of the polarization and jet angles altered, no such lag could be noted. The microflaring events, when analyzed as separate pulse emission components, were found to be characterized by a very high polarization degree ($> 30\%$) and polarization angles which differed substantially from the polarization angle of the underlying background component, or from the radio jet positional angle. We discuss the results in the general context of blazar emission and energy dissipation models.Comment: 16 pages, 17 Figures; ApJ accepte

A terminal assessment of stages theory : introducing a dynamic states approach to entrepreneurship

Stages of Growth models were the most frequent theoretical approach to understanding entrepreneurial business growth from 1962 to 2006; they built on the growth imperative and developmental models of that time. An analysis of the universe of such models (N=104) published in the management literature shows no consensus on basic constructs of the approach, nor is there any empirical confirmations of stages theory. However, by changing two propositions of the stages models, a new dynamic states approach is derived. The dynamic states approach has far greater explanatory power than its precursor, and is compatible with leading edge research in entrepreneurship

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Ustekinumab as Induction and Maintenance Therapy for Crohn’s Disease

BACKGROUND Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohn’s disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy. METHODS We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohn’s Disease Activity Index [CDAI] score of ≥100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150). RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with P≤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups. CONCLUSIONS Among patients with moderately to severely active Crohn’s disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types