Three-dimensional femtosecond laser nanolithography of crystals

Nanostructuring hard optical crystals has so far been exclusively feasible at their surface, as stress induced crack formation and propagation has rendered high precision volume processes ineffective. We show that the inner chemical etching reactivity of a crystal can be enhanced at the nanoscale by more than five orders of magnitude by means of direct laser writing. The process allows to produce cm-scale arbitrary three-dimensional nanostructures with 100 nm feature sizes inside large crystals in absence of brittle fracture. To showcase the unique potential of the technique, we fabricate photonic structures such as sub-wavelength diffraction gratings and nanostructured optical waveguides capable of sustaining sub-wavelength propagating modes inside yttrium aluminum garnet crystals. This technique could enable the transfer of concepts from nanophotonics to the fields of solid state lasers and crystal optics.Comment: Submitted Manuscript and Supplementary Informatio

Efficacy and safety of enzyme replacement therapy with BMN 110 (elosulfase alfa) for Morquio A syndrome (mucopolysaccharidosis IVA): a phase 3 randomised placebo-controlled study.

ObjectiveTo assess the efficacy and safety of enzyme replacement therapy (ERT) with BMN 110 (elosulfase alfa) in patients with Morquio A syndrome (mucopolysaccharidosis IVA).MethodsPatients with Morquio A aged ≥5 years (N = 176) were randomised (1:1:1) to receive elosulfase alfa 2.0 mg/kg/every other week (qow), elosulfase alfa 2.0 mg/kg/week (weekly) or placebo for 24 weeks in this phase 3, double-blind, randomised study. The primary efficacy measure was 6-min walk test (6MWT) distance. Secondary efficacy measures were 3-min stair climb test (3MSCT) followed by change in urine keratan sulfate (KS). Various exploratory measures included respiratory function tests. Patient safety was also evaluated.ResultsAt week 24, the estimated mean effect on the 6MWT versus placebo was 22.5 m (95 % CI 4.0, 40.9; P = 0.017) for weekly and 0.5 m (95 % CI -17.8, 18.9; P = 0.954) for qow. The estimated mean effect on 3MSCT was 1.1 stairs/min (95 % CI -2.1, 4.4; P = 0.494) for weekly and -0.5 stairs/min (95 % CI -3.7, 2.8; P = 0.778) for qow. Normalised urine KS was reduced at 24 weeks in both regimens. In the weekly dose group, 22.4 % of patients had adverse events leading to an infusion interruption/discontinuation requiring medical intervention (only 1.3 % of all infusions in this group) over 6 months. No adverse events led to permanent treatment discontinuation.ConclusionsElosulfase alfa improved endurance as measured by the 6MWT in the weekly but not qow dose group, did not improve endurance on the 3MSCT, reduced urine KS, and had an acceptable safety profile

KONSELINGNARATIF UNTUK MENGEMBANGKAN REGULASI DIRI (SELF REGULATION)SISWA SMA KOTA BANDAR LAMPUNG

Penelitian dilatarbelakangi oleh fenomena belum optimalnya regulasi diri remaja di SMA sehingga menimbulkan perilaku yang tidak sesuai dengan norma dan etika. Penelitian ini bertujuan menguji keefektivan konseling naratif untuk mengembangkan regulasi diri siswa SMA. Penelitian menggunakan pendekatan explanatory mixed methode dengan desain quasi-eksperimen. Populasi penelitian yaitu siswa kelas XI SMA Kota Bandarlampung Tahun Ajaran 2016/2017 dengan sampel penelitian sebanyak 794 orang siswa. Hasil penelitian menunjukkan (1) konseling naratif secara empirik terbukti efektif untuk mengembangkan regulasi diri siswa kelas XI SMA Kota Bandarlampung baik pada analisis total, aspek, maupun pada analisis indikator, (2) setelah mengikuti konseling naratif profil regulasi diri siswa kelas XI SMAN Kota Bandarlampung tahun ajaran 2016/2017 yang berada pada kategori sedang dan tinggi semakin bertambah banyak sedangkan pada kategori rendah semakin berkurang, (3) tidak ada perbedaan perkembangan regulasi diri antara siswa laki-laki dengan siswa perempuan Kelas XI SMA Kota Bandarlampung setelah konseling naratif, (4) ada perbedaan perkembangan regulasi diri antara siswa sekolah lower dengan siswa sekolah favorit setelah mengikuti konseling naratif. Siswa sekolah lower secara empirik terbukti memiliki regulasi diri lebih tinggi dibanding siswa sekolah favorit, dan (5) tidak ada perbedaan perkembangan regulasi diri antara siswa IPA dengan IPS Kelas XI SMA Kota Bandarlampung setelah mengikuti konseling naratif. Hasil penelitian ini direkomendasikan kepada guru Bimbingan dan Konseling/ Konselor, yakni implementasi konseling naratif dalam setting kelompok mengikuti tahapan: membentuk kelompok, ekternalisasi masalah kelompok, mengembangkan cerita, membentuk karakter konseli agar terpisah dengan masalah, membangun cerita, idetifikasi diri konseli, penguatan, menemukan cerita alternatif, dan perayaan. Bagi penelitian selanjutnya adalah melakukan penelitian konseling naratif untuk mengembangkan regulasi diri siswa dengan setting individual baik bagi siswa SMA, SMK, SMP, MTs, SD maupun MI. ;---The Study is based on the phenomenon where self regulation on adolescent hasn’t been optimal in Senior High School so it causes the inappropriate behavior towards norm and ethic. This study aim the effectiveness of narrative counseling to develop self regulation of Senior High School student. This study use explanatory mix methode approach with Quation Experimental Design. Population of this study is the student of Senior High School grade XI in Bandarlampung City on Academic Year 2016/2017 with 794 students as study’s sample. The Result of this study shows that (1) narrative counseling has been proven effectively to develop self regulation of the student of Senior High School grade XI in Bandarlampung City, whether on total analysis, aspect, or analysis indicator (2) after participating in the narrative counseling profile of the student of Senior High School grade XI in Bandarlampung City on Academic Year 2016/2017 on middle and high category become much more, while the low category decrease, (3) there is no difference on the development between male student and female student of Senior High School grade XI in Bandarlampung City after narrative counseling. (4) there is difference of the self regulation development between student of lower school with student of favourite school, and (5) there is no difference of the self regulation development between Science Student with Social Student of Senior High School grade XI in Bandarlampung City after participating in narrative counseling. The Result of this study is recommended to the teacher of Guidance and Counseling/Counselor, specifically the implementation of narrative counseling in group setting following the steps: forming the group, externalization of group problem, building the story, self-identification of counselee, strengthening, finding alternative story, and celebration. The upcoming study is about conducting narrative counseling experiment to develop student’s self regulation with individual setting whether for Senior High School, Vocational High School, Midle High School, MTs, Elementary School or MI

Effects of PREPARE, a Multi-component, School-Based HIV and Intimate Partner Violence (IPV) Prevention Programme on Adolescent Sexual Risk Behaviour and IPV : Cluster Randomised Controlled Trial

Young South Africans, especially women, are at high risk of HIV. We evaluated the effects of PREPARE, a multi-component, school-based HIV prevention intervention to delay sexual debut, increase condom use and decrease intimate partner violence (IPV) among young adolescents. We conducted a cluster RCT among Grade eights in 42 high schools. The intervention comprised education sessions, a school health service and a school sexual violence prevention programme. Participants completed questionnaires at baseline, 6 and 12 months. Regression was undertaken to provide ORs or coefficients adjusted for clustering. Of 6244 sampled adolescents, 55.3 % participated. At 12 months there were no differences between intervention and control arms in sexual risk behaviours. Participants in the intervention arm were less likely to report IPV victimisation (35.1 vs. 40.9 %; OR 0.77, 95 % CI 0.61-0.99; t(40) = 2.14) suggesting the intervention shaped intimate partnerships into safer ones, potentially lowering the risk for HIV

Outcome measures in chronic obstructive pulmonary disease (COPD): strengths and limitations

Current methods for assessing clinical outcomes in COPD mainly rely on physiological tests combined with the use of questionnaires. The present review considers commonly used outcome measures such as lung function, health status, exercise capacity and physical activity, dyspnoea, exacerbations, the multi-dimensional BODE score, and mortality. Based on current published data, we provide a concise overview of the principles, strengths and weaknesses, and discuss open questions related to each methodology. Reviewed is the current set of markers for measuring clinically relevant outcomes with particular emphasis on their limitations and opportunities that should be recognized when assessing and interpreting their use in clinical trials of COPD

The Effectiveness and Micro-costing Analysis of a Universal, School-Based, Social–Emotional Learning Programme in the UK: A Cluster-Randomised Controlled Trial

There are a growing number of school-based interventions designed to promote children’s social and emotional learning. One such intervention, PATHS (Promoting Alternative Thinking Strategies), was evaluated in a randomised controlled trial involving 5074 pupils aged 4–6 years at baseline in 56 primary schools across a large city in the UK. The programme was implemented for two academic years. The primary outcome measure was the teacher-rated Strengths and Difficulties Questionnaire (SDQ). A secondary measure was the PATHS Teacher Rating Scale (PTRS). Observations of child and teacher behaviours were undertaken in a third of intervention and control schools using the Teacher–Pupil Observation Tool (T-POT). Regarding fidelity, dose and adherence were measured via weekly logs completed by teachers, and a semi-structured questionnaire completed by PATHS coaches was used as a global measure of fidelity (capturing adherence, dose and quality). A cost-consequence analysis examined programme costs from a multi-agency public sector perspective. At 1 year post-baseline, there were no statistically significant differences between the programme and control groups on the SDQ subscales or the SDQ total difficulties and impact scores. There were statistically significant differences favouring the programme group for six out of 11 subscales on the secondary outcome measure (PTRS). At 2 years post-baseline, there were no statistically significant differences between the groups on either measure. Fidelity, according to the global measure, was relatively strong, and there was no relationship between fidelity and treatment effects. The average cost of PATHS was £12,666 per school or £139 per child. The study, which was fully powered and independent of the programme developer, shows no statistically significant effect of the programme on child behaviour or emotional well-being. Trial registration site and number: www.controlled-trials.com: ISRCTN 32534848

Speciation in the Deep Sea: Multi-Locus Analysis of Divergence and Gene Flow between Two Hybridizing Species of Hydrothermal Vent Mussels

International audienceBackground: Reconstructing the history of divergence and gene flow between closely-related organisms has long been a difficult task of evolutionary genetics. Recently, new approaches based on the coalescence theory have been developed to test the existence of gene flow during the process of divergence. The deep sea is a motivating place to apply these new approaches. Differentiation by adaptation can be driven by the heterogeneity of the hydrothermal environment while populations should not have been strongly perturbed by climatic oscillations, the main cause of geographic isolation at the surface. Methodology/Principal Finding: Samples of DNA sequences were obtained for seven nuclear loci and a mitochondrial locus in order to conduct a multi-locus analysis of divergence and gene flow between two closely related and hybridizing species of hydrothermal vent mussels, Bathymodiolus azoricus and B. puteoserpentis. The analysis revealed that (i) the two species have started to diverge approximately 0.760 million years ago, (ii) the B. azoricus population size was 2 to 5 time greater than the B. puteoserpentis and the ancestral population and (iii) gene flow between the two species occurred over the complete species range and was mainly asymmetric, at least for the chromosomal regions studied. Conclusions/Significance: A long history of gene flow has been detected between the two Bathymodiolus species. However, it proved very difficult to conclusively distinguish secondary introgression from ongoing parapatric differentiation. As powerful as coalescence approaches could be, we are left by the fact that natural populations often deviates from standard assumptions of the underlying model. A more direct observation of the history of recombination at one of the seven loci studied suggests an initial period of allopatric differentiation during which recombination was blocked between lineages. Even in the deep sea, geographic isolation may well be a crucial promoter of speciation