Dark-adapted rods consume oxygen at high rates and light adaptation decreases this oxygen burden and can have therapeutic effects on diabetic macular oedema (DMO).
Patients with mild ...non-proliferative diabetic retinopathy (DR) and early, untreated non-sight-threatening DMO slept for 6 months wearing masks that illuminated the eyelid of one closed eye by 505 nm light. Exclusion criteria were any concomitant eye disease, DR >ETDRS grade 35, and other systemic diseases.
change of OCT retinal thickness in the local region where oedema was present.
A total of 34 out of 40 patients completed the study. Mean baseline OCT macular cube thickness was equivalent for study and fellow eyes. But study eyes had a greater mean thickness in the central subfield zone 1 (282±53 μm) vs (256±19 μm) the fellow eyes. Twenty-eight study eyes showed intraretinal cysts compared with nine in the fellow eyes. At 6 months, only 19 study eyes had cysts while cysts were seen in 20 fellow eyes. After 6 months, the worst affected ETDRS zone and the central subfield zone 1 reduced in thickness in study eyes only by 12 μm (95% CI 20 to -7, P=0.01). The secondary outcomes of change in visual acuity, achromatic contrast sensitivity, and microperimetric thresholds improved significantly in study eyes and deteriorated in fellow eyes.
Sleeping in dim light that can keep rods light adapted may reverse the changes of DMO.
Antarctica has several apparent advantages for the study of biodiversity change along latitudinal gradients including a relatively pristine environment and simple community structures. Published ...analyses for lichens and mosses show no apparent gradient in biodiversity along the western Ross Sea coast line, the longest ice-free area in Antarctica spanning 14° latitude. One suggestion is that the area remains poorly surveyed. Here, we combine available species lists from four sites along the coast with new own data from two additional sites Taylor Valley (77°30′S) and Diamond Hill (79°S). We show a decline in total terrestrial biodiversity with latitude from Cape Hallett (72°S) to Diamond Hill. However, the southernmost site, the Queen Maud Mountains (84°S), is exceptional with almost the same diversity as Cape Hallett. A categorization of lichens according to their proposed ecology shows the proportion of tolerant species remains relatively constant. However, the absolute number of conformant species declines with latitude, again with a minimum at Diamond Hill. Similarity indices are low and not very different between sites with Diamond Hill being the exception with very few species. We suggest that terrestrial biodiversity best reflects microhabitat water availability rather than macroclimatic temperature changes and use climate data from Taylor Valley and Diamond Hill to support this suggestion. We propose that the importance of microhabitats and landscape location is one of several possible limitations to the application of bioclimatic modeling along the Ross sea coastline. In the absence of a definitive link between macroclimate and the biota, predicting the effects of climate changes will be more challenging.
To examine if there is a significant difference in survival between elderly (>50 years) and nonelderly adult patients receiving combination antiretroviral therapy in Uganda between 2004 and 2010.
...Prospective observational study.
Patients 18-49 years of age (nonelderly) and 50 years of age and older enrolled in the AIDS Support Organization Uganda HIV/AIDS national programme were assessed for time to all-cause mortality. We applied a Weibull multivariable regression.
Among the 22 087 patients eligible for analyses, 19 657 (89.0%) were aged between 18 and 49 years and 2430 (11.0%) were aged 50 years or older. These populations differed in terms of the distributions of sex, baseline CD4 cell count and death. The age group 40-44 displayed the lowest crude mortality rate 31.4 deaths per 1000 person-years; 95% confidence interval (CI) 28.1, 34.7) and the age group 60-64 displayed the highest crude mortality rate (58.9 deaths per 1000 person-years; 95% CI 42.2, 75.5). Kaplan-Meier survival estimates indicated that nonelderly patients had better survival than elderly patients (P < 0.001). Adjusted Weibull analysis indicated that elderly age status was importantly associated (adjusted hazard ratio 1.23, 95% CI 1.08-1.42) with mortality, when controlling for sex, baseline CD4 cell count and year of therapy initiation.
As antiretroviral treatment cohorts mature, the proportion of patients who are elderly will inevitably increase. Elderly patients may require focused clinical care that extends beyond HIV treatment.
In bit-patterned media (BPM), media noise is expected to be dominated by fabrication imperfections and to manifest as island size and spacing fluctuations. Previous work has shown that media noise ...has a significant impact on the error rates of BPM channels. Thus, having a realistic model of media noise is essential to evaluate the performance of the BPM channels. In this work, we apply image processing techniques to a scanning electron microscope image of a candidate BPM nano-mask, produced by a self-assembly technique, to estimate likely size and location fluctuations of the islands. These statistics may also be useful to characterize the samples of candidate BPM masks. We assume that these observed fluctuations are representative of patterning noise that might result from such a mask. The results indicate that these fluctuations are correlated and can be modeled by Gaussian random processes. Using estimated characteristics of islands size and location fluctuations, we model the correlated media noise and investigate the performance of BPM channels in the presence of such correlated media noise.
Reduced-representation sequencing methods have wide utility in conservation genetics of non-model species. Several methods are now available that reduce genome complexity to examine a wide range of ...markers in a large number of individuals. We produced two datasets collected using different laboratory techniques, comprising a common set of samples from the greater bilby (
Macrotis lagotis
). We examined the impact of differing data filtering thresholds on downstream population inferences. We found that choice of restriction enzyme and data filtering thresholds, especially the rate of allowable missing data, impacted our ability to detect population structure. Estimates of F
ST
were robust to alterations in laboratory and bioinformatic protocols while principal coordinates and STRUCTURE analyses showed variation according to the number of loci and percent missing data. We advise researchers using reduced-representation sequencing in conservation projects to examine a range of data thresholds, and follow these through to downstream population inferences. Multiple measures of population differentiation should be used in order to fully understand how data filtering thresholds influence the final dataset, paying particular attention to the impact of allowable missing data. Our results indicate that failure to follow these checks could impact conclusions drawn, and conservation management decisions made.
The reaction between nitrite and hemoglobin has been studied for over a century. However, recent evidence indicating nitrite is a latent vasodilatory agent that can be activated by its reaction with ...deoxyhemoglobin has led to renewed interest in this reaction. In this review we survey, in the context of our own recent studies, the chemical reactivity of nitrite with oxyhemoglobin, deoxyhemoglobin and methemoglobin, and place these reactions in both a physiological and pharmacological/therapeutic context.
Accurately estimating rates of disease progression is of central importance in developing mathematical models used to project outcomes and guide resource allocation decisions. Our objective was to ...specify a multivariate regression model to estimate changes in disease progression among individuals on highly active antiretroviral treatment in British Columbia, Canada, 1996-2011.
We used population-level data on disease progression and antiretroviral treatment utilization from the BC HIV Drug Treatment Program. Disease progression was captured using longitudinal CD4 and plasma viral load testing data, linked with data on antiretroviral treatment. The study outcome was categorized into (CD4 count ≥ 500, 500-350, 350-200, <200 cells/mm, and mortality). A 5-state continuous-time Markov model was used to estimate covariate-specific probabilities of CD4 progression, focusing on temporal changes during the study period.
A total of 210,083 CD4 measurements among 7421 individuals with HIV/AIDS were included in the study. Results of the multivariate model suggested that current highly active antiretroviral treatment at baseline, lower baseline CD4 (<200 cells/mm), and extended durations of elevated plasma viral load were each associated with accelerated progression. Immunological improvement was accelerated significantly from 2004 onward, with 23% and 46% increases in the probability of CD4 improvement from the fourth CD4 stratum (CD4 < 200) in 2004-2008 and 2008-2011, respectively.
Our results demonstrate the impact of innovations in antiretroviral treatment and treatment delivery at the population level. These results can be used to estimate a transition probability matrix flexible to changes in the observed mix of clients in different clinical stages and treatment regimens over time.
The aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing.
Patients with untreated stage IC-IV ...ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2–6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS).
Nine hundred and sixty-four patients were recruited from 71 centers. Dose escalation was achieved in 77% of patients who had ≥1 cycle. The median AUCs (cycle 2–6) received were 6.0 (Arm A) and 7.2 (Arm B) (P < 0.001). Grade 3/4 non-hematological toxicity was higher in Arm B (31% versus 22% P = 0.001). The median PFS was 12.1 months in Arm A and B hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.85–1.15; P = 0.93. The median overall survival (OS) was 34.1 and 30.7 months in Arms A and B, respectively (HR 0.98; 95% CI 0.81–1.18, P = 0.82). In multivariate analysis, baseline neutrophil (P < 0.001), baseline platelet counts (P < 0.001) and the difference between white blood cell (WBC) and neutrophil count (P = 0.009) had a significant adverse prognostic value.
Intrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia.
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