Senecio pokohinuensis (Asteraceae), a new combination for an endemic species of Mokohinau Islands, Hauraki Gulf (Tikapa Moana o Hauraki), northern Te Ika a Maui / North Island, Aotearoa / New Zealand

Previous research has demonstrated that Senecio repangae subsp. repangae and subsp. pokohinuensis have independent evolutionary origins. Here, we therefore elevate subsp. pokohinuensis to species rank: Senecio pokohinuensis. Updated morphological descriptions for both species are also provided

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

Control of Parasitophorous Vacuole Expansion by LYST/Beige Restricts the Intracellular Growth of Leishmania amazonensis

The intracellular protozoan Leishmania replicates in parasitophorous vacuoles (PV) that share many features with late endosomes/lysosomes. L. amazonensis PVs expand markedly during infections, but the impact of PV size on parasite intracellular survival is still unknown. Here we show that host cells infected with L. amazonensis upregulate transcription of LYST/Beige, which was previously shown to regulate lysosome size. Mutations in LYST/Beige caused further PV expansion and enhanced L. amazonensis replication. In contrast, LYST/Beige overexpression led to small PVs that did not sustain parasite growth. Treatment of LYST/Beige over-expressing cells with vacuolin-1 reversed this phenotype, expanding PVs and promoting parasite growth. The opposite was seen with E-64d, which reduced PV size in LYST-Beige mutant cells and inhibited L. amazonensis replication. Enlarged PVs appear to protect parasites from oxidative damage, since inhibition of nitric oxide synthase had no effect on L. amazonensis viability within large PVs, but enhanced their growth within LYST/Beige-induced small PVs. Thus, the upregulation of LYST/Beige in infected cells functions as a host innate response to limit parasite growth, by reducing PV volume and inhibiting intracellular survival

A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia

BACKGROUND: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 μg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS: The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.)

Macular thickness measurements in healthy Norwegian volunteers: an optical coherence tomography study

<p>Abstract</p> <p>Background</p> <p>Ethnic, intersubject, interoperator and intermachine differences in measured macular thickness seem to exist. Our purpose was to collect normative macular thickness data in Norwegians and to evaluate the association between macular thickness and age, gender, parity, and contraception status.</p> <p>Methods</p> <p>Retinal thickness was measured by Stratus Optical Coherence Tomography in healthy subjects. Mean macular thickness (MMT) was analyzed by repeated measures ANOVA with three dependent regional MMT-variables for interaction with age, gender, parity and oral contraception use. Exploratory correlation with age by the Pearson correlation test, both before and after stratification by gender was performed. Differences in MMT between older and younger subjects, between oral contraception users and non-users, as well as parous and nulliparous women were studied by post-hoc Student's t-tests.</p> <p>Results</p> <p>Central MMT in Norwegians was similar to values earlier reported in whites. MMT in central areas of 1 and 2.25 mm in diameter were higher in males than in females. In younger subjects (≤43 years) differences in MMT between genders were larger than in the mixed age group, whereas in older subjects (>43 years) the small differences did not reach the set significance level. No differences were found in minimal foveolar thickness (MMFT) between the genders in any age group.</p> <p>Mean foveal thickness (1 mm in diameter) was positively associated with age in females (r = 0.28, p = 0.03). MMFT was positively associated with age in all groups and reached significance both in females and in mixed gender group (r = 0.20, p = 0.041 and r = 0.26, p = 0.044 respectively).</p> <p>Mean foveal thickness and MMFT were significantly higher in parous than in nulliparous women, and age-adjusted ANOVA for MMFT revealed a borderline effect of parity.</p> <p>Conclusions</p> <p>Age and gender should be taken into consideration when establishing normal ranges for MMT in younger subjects. The gender difference in retinal thickness in young, but not older adults suggests a gonadal hormonal influence. The possible association between parity and retinal structure and its clinical relevance, should be studied further.</p

Record linked retrospective cohort study of 4.6 million people exploring ethnic variations in disease: myocardial infarction in South Asians

Background Law and policy in several countries require health services to demonstrate that they are promoting racial/ethnic equality. However, suitable and accurate data are usually not available. We demonstrated, using acute myocardial infarction, that linkage techniques can be ethical and potentially useful for this purpose. Methods The linkage was based on probability matching. Encryption of a unique national health identifier (the Community Health Index (CHI)) ensured that information about health status and census-based ethnicity could not be ascribed to an identified individual. We linked information on individual ethnic group from the 2001 Census to Scottish hospital discharge and mortality data. Results Overall, 94% of the 4.9 million census records were matched to a CHI record with an estimated false positive rate of less than 0.1 %, with 84.9 – 87.6% of South Asians being successfully linked. Between April 2001 and December 2003 there were 126 first episodes of acute myocardial infarction (AMI) among South Asians and 30,978 among non-South Asians. The incidence rate ratio was 1.45 (95% CI 1.17, 1.78) for South Asian compared to non-South Asian men and 1.80 (95% CI 1.31, 2.48) for South Asian women. After adjustment for age, sex and any previous admission for diabetes the hazard ratio for death following AMI was 0.59 (95% CI 0.43, 0.81), reflecting better survival among South Asians. Conclusion The technique met ethical, professional and legal concerns about the linkage of census and health data and is transferable internationally wherever the census (or population register) contains ethnic group or race data. The outcome is a retrospective cohort study. Our results point to increased incidence rather than increased case fatality in explaining high CHD mortality rate. The findings open up new methods for researchers and health planners

Optical Coherence Tomography in the UK Biobank Study – Rapid Automated Analysis of Retinal Thickness for Large Population-Based Studies

Purpose: To describe an approach to the use of optical coherence tomography (OCT) imaging in large, population-based studies, including methods for OCT image acquisition, storage, and the remote, rapid, automated analysis of retinal thickness. Methods: In UK Biobank, OCT images were acquired between 2009 and 2010 using a commercially available “spectral domain” OCT device (3D OCT-1000, Topcon). Images were obtained using a raster scan protocol, 6 mm x 6 mm in area, and consisting of 128 B-scans. OCT image sets were stored on UK Biobank servers in a central repository, adjacent to high performance computers. Rapid, automated analysis of retinal thickness was performed using custom image segmentation software developed by the Topcon Advanced Biomedical Imaging Laboratory (TABIL). This software employs dual-scale gradient information to allow for automated segmentation of nine intraretinal boundaries in a rapid fashion. Results: 67,321 participants (134,642 eyes) in UK Biobank underwent OCT imaging of both eyes as part of the ocular module. 134,611 images were successfully processed with 31 images failing segmentation analysis due to corrupted OCT files or withdrawal of subject consent for UKBB study participation. Average time taken to call up an image from the database and complete segmentation analysis was approximately 120 seconds per data set per login, and analysis of the entire dataset was completed in approximately 28 days. Conclusions: We report an approach to the rapid, automated measurement of retinal thickness from nearly 140,000 OCT image sets from the UK Biobank. In the near future, these measurements will be publically available for utilization by researchers around the world, and thus for correlation with the wealth of other data collected in UK Biobank. The automated analysis approaches we describe may be of utility for future large population-based epidemiological studies, clinical trials, and screening programs that employ OCT imaging