Mosaic: a position-effect variegation eye-color mutant in the mosquito Anopheles gambiae

The Mosaic (Mos) mutation, isolated in the F1 of 60Co-irradiated mosquitoes, confers variegated eye color to third and fourth instar larvae, pupae, and adults of the mosquito Anopheles gambiae. Mos is recessive in wild pink eye (p+) individuals, but is dominant and confers areas of wild-type pigment in mutant pink eye backgrounds. Mos is located 14.4 cM from pink eye on the X chromosome and is associated with a duplication of division 2B euchromatin that has been inserted into division 6 heterochromatin. Various combinations of Mos, pink eye alleles, and the autosomal mutation red eye were produced. In all cases, the darker pigmented regions of the eye in Mos individuals show the phenotypic interactions expected if the phenotype of those regions is due to expression of a p+ allele. Expression of Mos is suppressed by rearing larvae at 32 degrees C relative to 22 degrees C. All of these characteristics are consistent with Mos being a duplicated wild copy of the pink eye gene undergoing position-effect variegation.     

The Blood Pressure "Uncertainty Range" - a pragmatic approach to overcome current diagnostic uncertainties (II)

A tremendous amount of scientific evidence regarding the physiology and physiopathology of high blood pressure combined with a sophisticated therapeutic arsenal is at the disposal of the medical community to counteract the overall public health burden of hypertension. Ample evidence has also been gathered from a multitude of large-scale randomized trials indicating the beneficial effects of current treatment strategies in terms of reduced hypertension-related morbidity and mortality.In spite of these impressive advances and, deeply disappointingly from a public health perspective, the real picture of hypertension management is overshadowed by widespread diagnostic inaccuracies (underdiagnosis, overdiagnosis) as well as by treatment failures generated by undertreatment, overtreatment, and misuse of medications.The scientific, medical and patient communities as well as decision-makers worldwide are striving for greatest possible health gains from available resources.A seemingly well-crystallised reasoning is that comprehensive strategic approaches must not only target hypertension as a pathological entity, but rather, take into account the wider environment in which hypertension is a major risk factor for cardiovascular disease carrying a great deal of our inheritance, and its interplay in the constellation of other, well-known, modifiable risk factors, i.e., attention is to be switched from one's "blood pressure level" to one's absolute cardiovascular risk and its determinants. Likewise, a risk/benefit assessment in each individual case is required in order to achieve best possible results.Nevertheless, it is of paramount importance to insure generalizability of ABPM use in clinical practice with the aim of improving the accuracy of a first diagnosis for both individual treatment and clinical research purposes. Widespread adoption of the method requires quick adjustment of current guidelines, development of appropriate technology infrastructure and training of staff (i.e., education, decision support, and information systems for practitioners and patients). Progress can be achieved in a few years, or in the next 25 years.     

Effect of Comprehensive Oncogenetics Training Interventions for General Practitioners,Evaluated at Multiple Performance Levels

General practitioners (GPs) are increasingly called upon to identify patients at risk for hereditary cancers, and their genetic competencies need to be enhanced. This article gives an overview of a research project on how to build effective educational modules on genetics, assessed by randomized controlled trials (RCTs), reflecting the prioritized educational needs of primary care physicians. It also reports on an ongoing study to investigate long-term increase in genetic consultation skills (1-year follow-up) and interest in and satisfaction with a supportive website on genetics among GPs. Three oncogenetics modules were developed: an online Continuing Professional Development (G-eCPD) module, a live genetic CPD module, and a “GP and genetics” website (huisartsengenetica.nl) providing further genetics information applicable in daily practice. Three assessments to evaluate the effectiveness (1-year follow-up) of the oncogenetic modules were designed: 1.An online questionnaire on self-reported genetic competencies and changes in referral behaviour, 2.Referral rates from GPs to clinical genetics centres and 3.Satisfaction questionnaire and visitor count analytics of supportive genetics website. The setting was Primary care in the Netherlands and three groups of study participants were included in the reported studies:. Assessment 1. 168 GPs responded to an email invitation and were randomly assigned to an intervention or control group, evaluating the G-eCPD module (n = 80) or the live module (n = 88). Assessment 2. Referral rates by GPs were requested from the clinical genetics centres, in the northern and southern parts of the Netherlands (Amsterdam and Maastricht), for the two years before (2010 [n = 2510] and 2011 [n = 2940]) and the year after (2012 [n = 2875]) launch of the oncogenetics CPD modules and the website. Assessment 3. Participants of the website evaluation were all recruited online. When they visited the website during the month of February 2013, a pop-up invitation came up. Of the 1350 unique visitors that month, only 38 completed the online questionnaire. Main outcomes measure showed long-term (self-reported) genetic consultation skills (i.e. increased genetics awareness and referrals to clinical genetics centres) among GPs who participated in the oncogenetic training course, and interest in and satisfaction with the supportive website. 42 GPs (52%) who previously participated in the G-eCPD evaluation study and 50 GPs (57%) who participated in the live training programme responded to the online questionnaire on long-term effects of educational outcome. Previous RCTs showed that the genetics CPD modules achieved sustained improvement of oncogenetic knowledge and consultation skills (3-months follow-up). Participants of these RCTs reported being more aware of genetic problems long term; this was reported by 29 GPs (69%) and 46 GPs (92%) participating in the G-eCPD and live module evaluation studies, respectively (Chisquare test, p<0.005). One year later, 68% of the respondents attending the live training reported that they more frequently referred patients to the clinical genetics centres, compared to 29% of those who attended the online oncogenetics training (Chisquare test, p<0.0005). However, the clinical genetics centres reported no significant change in referral numbers one year after the training. Website visitor numbers increased, as did satisfaction, reflected in a 7.7 and 8.1 (out of 10) global rating of the website (by G-eCPD and live module participants, respectively). The page most often consulted was “family tree drawing”. Self-perceived genetic consultation skills increased long-term and GPs were interested in and satisfied with the supportive website. Further studies are necessary to see whether the oncogenetics CPD modules result in more efficient referral. The results presented suggest we have provided a flexible and effective framework to meet the need for effective educational programmes for non-geneticist healthcare providers, enabling improvement of genetic medical care.     

Spatial phylogenetics of the native woody plant species in Hainan,China

To better identify biodiversity hotspots for conservation on Hainan Island, a tropical island in southern China, we assessed spatial variation in phylogenetic diversity and species richness using 18,976 georeferenced specimen records and a newly reconstructed molecular phylogeny of 957 native woody plants. Within this framework, we delineated bioregions based on vegetation composition and mapped areas of neoendemism and paleoendemism to identify areas of priority for conservation. Our results reveal that the southwest of Hainan is the most important hot spot for endemism and plant diversity followed by the southeast area. The distribution of endemic species showed a scattered, rather than clustered, pattern on the island. Based on phylogenetic range‐weighted turnover metrics, we delineated three major vegetational zones in Hainan. These largely correspond to natural secondary growth and managed forests (e.g., rubber and timber forests) in central Hainan, old‐growth forests and natural secondary growth forest at the margins of Hainan, and nature reserves on the island (e.g., Jianfeng and Diaoluo National Nature Reserves). Our study helps to elucidate potential botanical conservation priorities for Hainan within an evolutionary, phylogenetic framework.     

Hochstetter's frog (Leiopelma hochstetteri) egg,mobile larvae and froglet development

Egg strings and larvae of Hochstetter's frog (Leiopelma hochstetteri) were located at three widely separated North Island sites: in seeps at Brynderwyns in December 2004, in an open pool at Wharerino in March 2009, and in an underground pool near the Kaipawa Track, Coromandel, in late May 2009. Ten egg strings were also laid by captive frogs in water courses at Hamilton Zoo in April 2009. All egg strings held from 11 to 13 eggs. The egg strings laid in the Brynderwyns were regularly observed until metamorphosis was completed in March 2005. Twenty-four swimming larvae emerged from 25 capsules at c. 40 days after discovery, and at least 14 froglets were produced at c. 90 days. All of them developed in darkness, in a 120 ml pool <30 mm deep. The emerged froglets ranged from 9.8 to 10.8 mm snout-vent length. The detection of eggs, larvae and <11 mm froglets indicates that the egg laying period is at least from late September to May.