545 research outputs found
Drosophila anterior determination is independent of bicoid morphogenic functions but depends on activating versus repressing inputs on the level of target gene enhancers.
Low Space External Memory Construction of the Succinct Permuted Longest Common Prefix Array
The longest common prefix (LCP) array is a versatile auxiliary data structure
in indexed string matching. It can be used to speed up searching using the
suffix array (SA) and provides an implicit representation of the topology of an
underlying suffix tree. The LCP array of a string of length can be
represented as an array of length words, or, in the presence of the SA, as
a bit vector of bits plus asymptotically negligible support data
structures. External memory construction algorithms for the LCP array have been
proposed, but those proposed so far have a space requirement of words
(i.e. bits) in external memory. This space requirement is in some
practical cases prohibitively expensive. We present an external memory
algorithm for constructing the bit version of the LCP array which uses
bits of additional space in external memory when given a
(compressed) BWT with alphabet size and a sampled inverse suffix array
at sampling rate . This is often a significant space gain in
practice where is usually much smaller than or even constant. We
also consider the case of computing succinct LCP arrays for circular strings
Isotope shift in the dielectronic recombination of three-electron ^{A}Nd^{57+}
Isotope shifts in dielectronic recombination spectra were studied for Li-like
^{A}Nd^{57+} ions with A=142 and A=150. From the displacement of resonance
positions energy shifts \delta E^{142,150}(2s-2p_1/2)= 40.2(3)(6) meV
(stat)(sys)) and \delta E^{142,150}(2s-2p_3/2) = 42.3(12)(20) meV of 2s-2p_j
transitions were deduced. An evaluation of these values within a full QED
treatment yields a change in the mean-square charge radius of ^{142,150}\delta
= -1.36(1)(3) fm^2. The approach is conceptually new and combines the
advantage of a simple atomic structure with high sensitivity to nuclear size.Comment: 10 pages, 3 figures, accepted for publication in Physical Review
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Efficient Synthesis of Novel Plasticizers by Direct Palladium-Catalyzed Di- or Multi-carbonylations
Diesters are of fundamental importance in the chemical industry and are used for many applications, e.g. as plasticizers, surfactants, emulsifiers, and lubricants. Herein, we present a straightforward and efficient method for the selective synthesis of diesters via palladium-catalyzed direct carbonylation of di- or polyols with readily available alkenes. Key-to-success is the use of a specific palladium catalyst with the âbuilt-in-baseâ ligand L16 providing esterification of all alcohols and a high n/iso ratio. The synthesized diesters were evaluated as potential plasticizers in PVC films by measuring the glass transition temperature (Tg) via differential scanning calorimetry (DSC)
Attitude towards and factors affecting uptake of population based BRCA testing in the Ashkenazi Jewish population: a cohort study
Objective
To evaluate factors affecting unselectedâpopulationâbasedâBRCAâtesting in AshkenaziâJews (AJ).
Design
Cohortâstudy set within recruitment to the GCaPPSâtrial (ISRCTN73338115).
Setting
NorthâLondon AJâpopulation.
Population or Sample
AJ women/men >18âyears, recruited through selfâreferral.
Methods
AJâwomen/men underwent preâtest counselling for BRCAâtesting through recruitment clinics (clusters). Consenting individuals provided bloodâsample for BRCAâtesting. Socioâdemographic/familyâhistory/knowledge/psychological wellâbeing data alongâwith benefits/risks/culturalâinfluences (18âitemâquestionnaire measuring âattitudeâ) were collected.
4âitem likertâscales analysed initial âinterestâ and âintentionâtoâtestâ preâcounselling. Uniâ&âmultivariable logisticâregressionâmodels evaluated factors affecting uptake/interest/intentionâto undergo BRCAâtesting. Statistical inference was based on cluster robust standardâerrors and joint Waldâtests for significance. ItemâResponseâTheory and gradedâresponseâmodels modelled responses to 18âitem questionnaire.
Main Outcome Measures
Interest, intention, uptake, attitude towards BRCAâtesting.
Results
935 (women=67%/men=33%; meanâage=53.8(S.D=15.02) years) individuals underwent preâtest geneticâcounselling. Preâcounselling 96% expressed interest but 60% indicated clear intentionâto undergo BRCAâtesting. Subsequently 88% opted for BRCAâtesting. BRCAârelated knowledge (p=0.013) and degreeâlevel education(p=0.01) were positively and negatively (respectively) associated with intentionâtoâtest. Being married/cohabiting had fourâfold higherâodds for BRCAâtesting uptake (p=0.009). Perceived benefits were associated with higher preâcounselling odds for interest and intentionâto undergo BRCAâtesting. Reduced uncertainty/reassurance were the most important factors contributing to decisionâmaking. Increased importance/concern towards risks/limitations (confidentiality/insurance/emotionalâimpact/inability to prevent cancer/marriageâability/ethnicâfocus/stigmatization) were significantly associated with lowerâodds of uptakeâof BRCAâtesting, and discriminated between acceptors and decliners. Maleâgender/degreeâlevelâeducation (p=0.001) had weaker, while having children had stronger (p=0.005) attitudes towards BRCAâtesting.
Conclusions
BRCAâtesting in the AJâpopulation has high acceptability. Preâtest counselling increases awareness of disadvantages/limitations of BRCAâtesting, influencing final costâbenefit perception and decisionâmaking on undergoing testing.
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Genetic Diagnostics in Routine Osteological Assessment of Adult Low Bone Mass Disorders
Context Many different inherited and acquired conditions can result in premature bone fragility / low bone mass disorders (LBMD). Objective We aimed at elucidating the impact of genetic testing on differential diagnosis of adult LBMD and at defining clinical criteria for predicting monogenic forms. Methods Four clinical centers broadly recruited a cohort of 394 unrelated adult women before menopause and men younger than 55 years with a bone mineral density (BMD) Z-score 2), and a high normal BMI. In contrast, mutation frequencies did not correlate with age, prevalent vertebral fractures, BMD, or biochemical parameters. In individuals without monogenic disease-causing rare variants, common variants predisposing for low BMD, e.g. in LRP5, were overrepresented. Conclusion The overlapping spectra of monogenic adult LBMD can be easily disentangled by genetic testing and the proposed clinical criteria can help to maximize the diagnostic yield
J Musculoskelet Neuronal Interact
Long-term bed-rest is used to simulate the effect of spaceflight on the human body and test different kinds of countermeasures. The 2nd Berlin BedRest Study (BBR2-2) tested the efficacy of whole-body vibration in addition to high-load resisitance exercise in preventing bone loss during bed-rest. Here we present the protocol of the study and discuss its implementation. Twenty-four male subjects underwent 60-days of six-degree head down tilt bed-rest and were randomised to an inactive control group (CTR), a high-load resistive exercise group (RE) or a high-load resistive exercise with whole-body vibration group (RVE). Subsequent to events in the course of the study (e.g. subject withdrawal), 9 subjects participated in the CTR-group, 7 in the RVE-group and 8 (7 beyond bed-rest day-30) in the RE-group. Fluid intake, urine output and axiallary temperature increased during bed-rest (p or = .17). Body weight changes differed between groups (p < .0001) with decreases in the CTR-group, marginal decreases in the RE-group and the RVE-group displaying significant decreases in body-weight beyond bed-rest day-51 only. In light of events and experiences of the current study, recommendations on various aspects of bed-rest methodology are also discussed
POPULATION-BASED TESTING FOR BRCA MUTATIONS (COMPARED TO FAMILY-HISTORY BASED TESTING) MAY BE COST SAVING IN ASHKENAZI-JEWS: A HEALTH-ECONOMICS DECISION ANALYTICAL MODEL
Randomised trial of population-based BRCA testing in Ashkenazi Jews: long-term outcomes
© 2019 Royal College of Obstetricians and Gynaecologists Objective: Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximise primary prevention for breast-and-ovarian cancer. We compare long-term outcomes of population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life. Design: Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS); (ii) FH/clinical-criteria-based testing. Setting: North London Ashkenazi-Jewish (AJ) population. Population/Sample: AJ women/men. Methods: Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population. Inclusion criteria: AJ women/men >18 years old; exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers. Interventions: Genetic testing for three Jewish BRCA founder-mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm; (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality-of-life outcomes over 3 years. Main outcome measures: Validated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality-of-life outcomes at baseline/1-year/2-year/3-year follow up. Results: In all, 1034 individuals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety-&-depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health-anxiety (P < 0.0005) and quality-of-life (P = 0.004) scores in both PS and FH groups over time. Eighteen of 30 (60%) BRCA carriers identified did not fulfil clinical criteria for BRCA testing. Total BRCA prevalence was 2.9% (95% CI 1.97â4.12%), BRCA1 prevalence was 1.55% (95% CI 0.89â2.5%) and BRCA2 prevalence was 1.35% (95% CI 0.74â2.26%). Conclusion: Population-based AJ BRCA testing does not adversely affect long-term psychological wellbeing or quality-of-life, decreases anxiety and could identify up to 150% additional BRCA carriers. Tweetable abstract: Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life
Cluster-randomised non-inferiority trial comparing DVD-assisted and traditional genetic counselling in systematic population testing for BRCA1/2 mutations.
BACKGROUND: Newer approaches to genetic counselling are required for population-based testing. We compare traditional face-to-face genetic counselling with a DVD-assisted approach for population-based BRCA1/2 testing. METHODS: A cluster-randomised non-inferiority trial in the London Ashkenazi Jewish population. INCLUSION CRITERIA: Ashkenazi Jewish men/women >18â
years; exclusion criteria: (a) known BRCA1/2 mutation, (b) previous BRCA1/2 testing and (c) first-degree relative of BRCA1/2 carrier. Ashkenazi Jewish men/women underwent pre-test genetic counselling prior to BRCA1/2 testing in the Genetic Cancer Prediction through Population Screening trial (ISRCTN73338115). Genetic counselling clinics (clusters) were randomised to traditional counselling (TC) and DVD-based counselling (DVD-C) approaches. DVD-C involved a DVD presentation followed by shorter face-to-face genetic counselling. Outcome measures included genetic testing uptake, cancer risk perception, increase in knowledge, counselling time and satisfaction (Genetic Counselling Satisfaction Scale). Random-effects models adjusted for covariates compared outcomes between TC and DVD-C groups. One-sided 97.5% CI was used to determine non-inferiority. SECONDARY OUTCOMES: relevance, satisfaction, adequacy, emotional impact and improved understanding with the DVD; cost-minimisation analysis for TC and DVD-C approaches. RESULTS: 936 individuals (clusters=256, mean-size=3.6) were randomised to TC (n=527, clusters=134) and DVD-C (n=409, clusters=122) approaches. Groups were similar at baseline, mean age=53.9 (SD=15) years, women=66.8%, men=33.2%. DVD-C was non-inferior to TC for increase in knowledge (d=-0.07; lower 97.5% CI=-0.41), counselling satisfaction (d=-0.38, 97.5% CI=1.2) and risk perception (d=0.08; upper 97.5% CI=3.1). Group differences and CIs did not cross non-inferiority margins. DVD-C was equivalent to TC for uptake of genetic testing (d=-3%; lower/upper 97.5% CI -7.9%/1.7%) and superior for counselling time (20.4 (CI 18.7 to 22.2) min reduction (p<0.005)). 98% people found the DVD length and information satisfactory. 85-89% felt it improved their understanding of risks/benefits/implications/purpose of genetic testing. 95% would recommend it to others. The cost of genetic counselling for DVD-C=ÂŁ7787 and TC=ÂŁ17â
307. DVD-C resulted in cost savings=ÂŁ9520 (ÂŁ14/volunteer). CONCLUSIONS: DVD-C is an effective, acceptable, non-inferior, time-saving and cost-efficient alternative to TC. TRIAL REGISTRATION NUMBER: ISRCTN 73338115
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