The RUSH2A Study: Best-Corrected Visual Acuity, Full-Field Electroretinography Amplitudes, and Full-Field Stimulus Thresholds at Baseline

Purpose: The purpose of this study was to evaluate baseline best corrected visual acuity (BCVA), full-field electroretinography (ERG), full-field stimulus thresholds (FST), and their relationship with baseline demographic and clinical characteristics in the Rate of Progression in Usher syndrome type 2 (USH2A)-related Retinal Degeneration (RUSH2A) multicenter study. Methods: Participants had Usher syndrome type 2 (USH2, N = 80) or autosomal recessive nonsyndromic retinitis pigmentosa (ARRP, N = 47) associated with biallelic variants in the USH2A gene. Associations of demographic and clinical characteristics with BCVA, ERG, and FST were assessed with regression models. Results: In comparison to ARRP, USH2 had worse BCVA (median 79 vs. 82 letters; P < 0.001 adjusted for age), lower rod-mediated ERG b-wave amplitudes (median 0.0 vs. 6.6 µV; P < 0.001) and 30 Hz flicker cone-mediated ERG amplitudes (median 1.5 vs. 3.1 µV; P = 0.001), and higher (white, blue, and red) FST thresholds (means [-26, -31, -23 dB] vs. [-39, -45, -28 dB]; P < 0.001 for all stimuli). After adjusting for age, gender, and duration of vision loss, the difference in BCVA between diagnosis groups was attenuated (P = 0.09). Only diagnosis was associated with rod- and cone-mediated ERG parameters, whereas both genders (P = 0.04) and duration of visual loss (P < 0.001) also were associated with FST white stimulus. Conclusions: USH2 participants had worse BCVA, ERG, and FST than ARRP participants. FST was strongly associated with duration of disease; it remains to be determined whether it will be a sensitive measure of progression. Translational Relevance: Using standardized research protocols in RUSH2A, measures have been identified to monitor disease progression and treatment response and differentiate features of prognostic relevance between USH2 and ARRP participants with USH2A mutations

Effectiveness, safety and acceptability of ‘see and treat' with cryotherapy by nurses in a cervical screening study in India

We evaluated a ‘see and treat' procedure involving screening, colposcopy, biopsy and cryotherapy by trained nurses in one-visit in field clinics in a cervical screening study in South India for its acceptability, safety and effectiveness in curing cervical intraepithelial neoplasia (CIN). Women positive on visual inspection with acetic acid (VIA) were advised colposcopy, directed biopsies and cryotherapy if they had colposcopic impression of CIN in one visit by nurses in field clinics supervised by a doctor. Side effects and complications were assessed and cure rates were evaluated with VIA, colposcopy and biopsy if colposcopic abnormalities were suspected. Cure was defined as no clinical or histological evidence of CIN at ⩾6 months from treatment. Of the 2513 women offered ‘see and treat' procedure, 1879 (74.8%) accepted. Of the 1397 women with histologically proved CIN treated with cryotherapy, 1026 reported for follow-up evaluation. Cure rates were 81.4% (752 out of 924) for women with CIN 1; 71.4% (55 out of 77) for CIN 2 and 68.0% (17 out of 25) for CIN 3. Minor side effects and complications were documented in less than 3% of women. ‘See and treat' with cryotherapy by nurses under medical supervision is acceptable, safe and effective for cervical cancer prevention in low-resource settings

Evaluation of 'see-see and treat' strategy and role of HIV on cervical cancer prevention in Uganda

<p>Abstract</p> <p>Background</p> <p>There is scant information on whether Human Immunodeficiency Virus (HIV) seropositivity has an influence on the outcome of treatment of precancerous cervical lesions using cryotherapy. We studied the prevalence of cervical abnormalities detectable by visual inspection and cervical lesions diagnosed by colposcopy according to HIV serostatus and described the outcomes of cryotherapy treatment.</p> <p>Methods</p> <p>Trained nurses examined women not previously screened for cervical cancer using visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) in two family planning/post natal clinics in Kampala, Uganda, from February 2007 to August 2008. Women with abnormal visual inspection findings were referred for colposcopic evaluation and HIV testing. Women with precancerous cervical lesions detected at colposcopy were treated mainly by cryotherapy, and were evaluated for treatment outcome after 3 months by a second colposcopy.</p> <p>Results</p> <p>Of the 5 105 women screened, 834 presented a positive screening test and were referred for colposcopy. Of these 625 (75%) returned for the colposcopic evaluation and were tested for HIV. For the 608 (97.5%) women in the age range 20-60 years, colposcopy revealed 169 women with cervical lesions: 128 had inflammation, 19 had low grade squamous intraepithelial lesion (LGSIL), 13 had high grade squamous intraepithelial lesion (HGSIL), 9 had invasive cervical cancer and 2 had inconclusive findings. Detection rates per 1 000 women screened were higher among the older women (41-60 years) compared to women aged 20-40 years. They were accordingly 55% and 20% for inflammation, 10% and 2% for LGSIL, 5% and 2% for HGSIL, 6% and 1% for invasive cervical cancer.</p> <p>Of the 608 women, 103 (16%) were HIV positive. HIV positivity was associated with higher likelihood of inflammation (RR = 1.7; 95% CI: 1.2-2.4).</p> <p>Conclusions</p> <p>Detection rates were higher among older women 41-60 years. Visual inspection of the cervix uteri with acetic acid (VIA) and Lugol's iodine (VILI) used as a sole method for cervical cancer screening would entail significant false positive results. HIV seropositivity was associated with a higher prevalence of inflammatory cervical lesions. In view of the small numbers and the relatively short follow up time of 3 months, we could not make an emphatic conclusion about the effect of HIV serostatus on cryotherapy treatment outcome.</p

Perceptions of, and reactions to, environmental heat: a brief note on issues of concern in relation to occupational health

Average temperatures around the world are already increasing, and climate change projections suggest that global mean temperatures will continue to rise. As the effects, and projected effects, of climate change are becoming clearer, it is more apparent that the health effects of heat exposure will need further investigation. The risks associated with heat exposure are especially relevant to understandings of occupational health for people involved in labouring or agricultural work in low-income countries. This review is a partial look at the ways in which issues surrounding heat exposure and occupational health have been treated in some of the available literature. This literature focuses on military-related medical understandings of heat exposure as well as heat exposure in working environments. The ways that these issues have been treated throughout the literature reflect the ways in which technologies of observation are intertwined with social attitudes. The effects of heat on the health of working people, as well as identification of risk groups, will require further research in order to promote prophylactic measures as well as to add to understandings of the actual and potential consequences of climatic change

Culture and Hybridization Experiments on an Ulva Clade Including the Qingdao Strain Blooming in the Yellow Sea

In the summer of 2008, immediately prior to the Beijing Olympics, a massive green tide of the genus Ulva covered the Qingdao coast of the Yellow Sea in China. Based on molecular analyses using the nuclear encoded rDNA internal transcribed spacer (ITS) region, the Qingdao strains dominating the green tide were reported to be included in a single phylogenetic clade, currently regarded as a single species. On the other hand, our detailed phylogenetic analyses of the clade, using a higher resolution DNA marker, suggested that two genetically separate entities could be included within the clade. However, speciation within the Ulva clade has not yet been examined. We examined the occurrence of an intricate speciation within the clade, including the Qingdao strains, via combined studies of culture, hybridization and phylogenetic analysis. The two entities separated by our phylogenetic analyses of the clade were simply distinguished as U. linza and U. prolifera morphologically by the absence or presence of branches in cultured thalli. The inclusion of sexual strains and several asexual strains were found in each taxon. Hybridizations among the sexual strains also supported the separation by a partial gamete incompatibility. The sexually reproducing Qingdao strains crossed with U. prolifera without any reproductive boundary, but a complete reproductive isolation to U. linza occurred by gamete incompatibility. The results demonstrate that the U. prolifera group includes two types of sexual strains distinguishable by crossing affinity to U. linza. Species identification within the Ulva clade requires high resolution DNA markers and/or hybridization experiments and is not possible by reliance on the ITS markers alone

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty