2,897 research outputs found
Emigrant and immigrant small-island profiles
This study examines a global sample of forty small islands less than three million in population,
14 characterized by chronic immigration and 26 typified by chronic emigration. It constructs
separate socio-economic and demographic profiles of the two island groups using means
difference analysis across twenty-two indicators. The paper concludes that the immigrant islands
are significantly more economically and socially advanced and demographically mature than
their emigrant counterparts. It argues indirectly that the source of the former’s affluence is their
greater degree of postwar diversification, especially towards international tourism, offshore
banking and export manufacturing.peer-reviewe
Tuning transcriptional regulation through signaling: A predictive theory of allosteric induction
Allosteric regulation is found across all domains of life, yet we still lack
simple, predictive theories that directly link the experimentally tunable
parameters of a system to its input-output response. To that end, we present a
general theory of allosteric transcriptional regulation using the
Monod-Wyman-Changeux model. We rigorously test this model using the ubiquitous
simple repression motif in bacteria by first predicting the behavior of strains
that span a large range of repressor copy numbers and DNA binding strengths and
then constructing and measuring their response. Our model not only accurately
captures the induction profiles of these strains but also enables us to derive
analytic expressions for key properties such as the dynamic range and
. Finally, we derive an expression for the free energy of allosteric
repressors which enables us to collapse our experimental data onto a single
master curve that captures the diverse phenomenology of the induction profiles.Comment: Substantial revisions for resubmission (3 new figures, significantly
elaborated discussion); added Professor Mitchell Lewis as another author for
his continuing contributions to the projec
The Energetics of Molecular Adaptation in Transcriptional Regulation
Mutation is a critical mechanism by which evolution explores the functional
landscape of proteins. Despite our ability to experimentally inflict mutations
at will, it remains difficult to link sequence-level perturbations to
systems-level responses. Here, we present a framework centered on measuring
changes in the free energy of the system to link individual mutations in an
allosteric transcriptional repressor to the parameters which govern its
response. We find the energetic effects of the mutations can be categorized
into several classes which have characteristic curves as a function of the
inducer concentration. We experimentally test these diagnostic predictions
using the well-characterized LacI repressor of Escherichia coli, probing
several mutations in the DNA binding and inducer binding domains. We find that
the change in gene expression due to a point mutation can be captured by
modifying only a subset of the model parameters that describe the respective
domain of the wild-type protein. These parameters appear to be insulated, with
mutations in the DNA binding domain altering only the DNA affinity and those in
the inducer binding domain altering only the allosteric parameters. Changing
these subsets of parameters tunes the free energy of the system in a way that
is concordant with theoretical expectations. Finally, we show that the
induction profiles and resulting free energies associated with pairwise double
mutants can be predicted with quantitative accuracy given knowledge of the
single mutants, providing an avenue for identifying and quantifying epistatic
interactions.Comment: 11 pages, 6 figures, supplemental info. available via
http://rpgroup.caltech.edu/mwc_mutant
Preventing Teen Relationship Abuse and Sexual Assault through Bystander Training: Intervention Outcomes for School Personnel
The purpose of the current study was to examine the impact of exposure to Bringing in the Bystander—High School Curriculum (BITB-HSC) on school personnel, which included a seven session classroom curriculum for ninth through twelfth graders (student curriculum), a bystander training workshop for school personnel (school personnel workshop), and reading materials (handout). We examined how exposure to these various BITB-HSC intervention components was associated with school personnel’s knowledge and bystander efficacy, intentions, and barriers specific to student relationship abuse (RA) and sexual assault (SA). Participants were 488 school personnel from 12 high schools in upper New England who completed the 4-month follow-up survey that assessed for intervention exposure (284 participants completed both the baseline and follow-up survey). Whereas 53% of participants were exposed to no intervention components, the other half of the sample were exposed to a combination of intervention components. Higher baseline knowledge and reactive bystander intentions were associated with subsequent exposure to both the student curriculum and the handout, and fewer barriers to bystander action predicted exposure to the school personnel workshop. Exposure to the school personnel workshop, student curriculum, and handout was associated with subsequent greater knowledge, exposure to the student curriculum predicted reactive bystander intentions, and exposure to the handout predicted higher reactive bystander intentions and bystander efficacy. Findings suggest that despite challenges with engagement, exposure to the BITB-HSC components may be a useful tool in improving school personnel’s responses to RA and SA among high school students
Three-year efficacy and safety of a new 52-mg levonorgestrel-releasing intrauterine system
AbstractObjectiveTo assess 3-year data on the efficacy and safety of a new 52-mg levonorgestrel intrauterine contraceptive (LNG20) designed for up to 7 years use.Study DesignNulliparous and parous women aged 16–45 years at enrollment with regular menstrual cycles and requesting contraception were enrolled in an open-label, partially randomized trial to evaluate LNG20. The primary outcome was pregnancy rate for women aged 16–35 years calculated as the Pearl Index. Women aged 36–45 years received LNG20 for safety evaluation only. All participants had in-person or phone follow-up approximately every 3 months during the study.ResultsA total of 1600 women aged 16–35 years and 151 women aged 36–45 years agreed to LNG20 placement, including 1011 (57.7%) nulliparous and 438 (25.1%) obese women. Successful placement occurred in 1714 (97.9%) women. Six pregnancies occurred, four of which were ectopic. The Pearl Index for LNG20 was 0.15 (95% CI 0.02–0.55) through Year 1, 0.26 (95% CI 0.10–0.57) through Year 2, and 0.22 (95% CI 0.08–0.49) through Year 3. The cumulative life-table pregnancy rate was 0.55 (95% CI 0.24–1.23) through 3 years. Expulsion was reported in 62 (3.5%) participants, most (50 [80.6%]) during the first year of use. Of women who discontinued LNG20 and desired pregnancy, 86.8% conceived spontaneously within 12 months. Pelvic infection was diagnosed in 10 (0.6%) women. Only 26 (1.5%) LNG20 users discontinued due to bleeding complaints.ConclusionThe LNG20 intrauterine system is highly effective and safe over 3 years of use in nulliparous and parous women.Implications statementA new 52-mg levonorgestrel-releasing intrauterine system is effective and safe for nulliparous and parous women for at least 3 years
Strategies to Reduce Non-Ventilator-Associated Hospital-Acquired Pneumonia: A Systematic Review
Background Point prevalence studies identify that pneumonia is the most common healthcare associated infection. However, non-ventilator associated healthcare associated pneumonia (NV-HAP) is both underreported and understudied. Most research conducted to date, focuses on ventilator associated pneumonia. We conducted a systematic review, to provide the latest evidence for strategies to reduce NV-HAP and describe the methodological approaches used. Methods We performed a systematic search to identify research exploring and evaluating NV-HAP preventive measures in hospitals and aged-care facilities. The electronic database Medline was searched, for peer-reviewed articles published between 1st January 1998 and 31st August 2018. An assessment of the study quality and risk of bias of included articles was conducted using the Newcastle–Ottawa Scale. Results The literature search yielded 1551 articles, with 15 articles meeting the inclusion criteria. The majority of strategies for NV-HAP prevention focussed on oral care (n = 9). Three studies evaluated a form of physical activity, such as passive movements, two studies used dysphagia screening and management; and another study evaluated prophylactic antibiotics. Most studies (n = 12) were conducted in a hospital setting. Six of the fifteen studies were randomised controlled trials. Conclusion There was considerable heterogeneity in the included studies, including the type of intervention, study design, methods and definitions used to diagnose the NV-HAP. To date, interventions to reduce NV-HAP appear to be based broadly on the themes of improving oral care, increased mobility or movement and dysphagia management
Metagenomic insights of the infant microbiome community structure and function across multiple sites in the United States
The gut microbiome plays an important role in early life, protecting newborns from enteric pathogens, promoting immune system development and providing key functions to the infant host. Currently, there are limited data to broadly assess the status of the US healthy infant gut microbiome. To address this gap, we performed a multi-state metagenomic survey and found high levels of bacteria associated with enteric inflammation (e.g. Escherichia, Klebsiella), antibiotic resistance genes, and signatures of dysbiosis, independent of location, age, and diet. Bifidobacterium were less abundant than generally expected and the species identified, including B. breve, B. longum and B. bifidum, had limited genetic capacity to metabolize human milk oligosaccharides (HMOs), while B. infantis strains with a complete capacity for HMOs utilization were found to be exceptionally rare. Considering microbiome composition and functional capacity, this survey revealed a previously unappreciated dysbiosis that is widespread in the contemporary US infant gut microbiome
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