Maximum Number of Habitable Planets at the Time of Earth's Origin: New Hints for Panspermia?

New discoveries have fuelled the ongoing discussion of panspermia, i.e. the transport of life from one planet to another within the solar system (interplanetary panspermia) or even between different planetary systems (interstellar panspermia). The main factor for the probability of interstellar panspermia is the average density of stellar systems containing habitable planets. The combination of recent results for the formation rate of Earth-like planets with our estimations of extrasolar habitable zones allows us to determine the number of habitable planets in the Milky Way over cosmological time scales. We find that there was a maximum number of habitable planets around the time of Earth's origin. If at all, interstellar panspermia was most probable at that time and may have kick-started life on our planet.     

ultraviolet radiation from F and K stars and implications for planetary habitability

Now that extrasolar planets have been found, it is timely to ask whether some of them might be suitable for life. Climatic constraints on planetary habitability indicate that a reasonably wide habitable zone exists around main sequence stars with spectral types in the early-F to mid-K range. However, it has not been demonstrated that planets orbiting such stars would be habitable when biologically-damaging energetic radiation is also considered. The large amounts of UV radiation emitted by early-type stars have been suggested to pose a problem for evolving life in their vicinity. But one might also argue that the real problem lies with late-type stars, which emit proportionally less radiation at the short wavelengths ( < 200 nm) required to split O2 and initiate ozone formation. We show here that neither of these concerns is necessarily fatal to the evolution of advanced life: Earth-like planets orbiting F and K stars may well receive less harmful UV radiation at their surfaces than does the Earth itself.     

An Integrated Mass-Spectrometry Pipeline Identifies Novel Protein Coding-Regions in the Human Genome

Background

Most protein mass spectrometry (MS) experiments rely on searches against a database of known or predicted proteins, limiting their ability as a gene discovery tool.

Results

Using a search against an in silico translation of the entire human genome, combined with a series of annotation filters, we identified 346 putative novel peptides [False Discovery Rate (FDR)<5%] in a MS dataset derived from two human breast epithelial cell lines. A subset of these were then successfully validated by a different MS technique. Two of these correspond to novel isoforms of Heterogeneous Ribonuclear Proteins, while the rest correspond to novel loci.

Conclusions

MS technology can be used for ab initio gene discovery in human data, which, since it is based on different underlying assumptions, identifies protein-coding genes not found by other techniques. As MS technology continues to evolve, such approaches will become increasingly powerful.     

Public Hygiene Campaign in Denmark during the 2009 H1N1 Pandemic Had No Effect on Hospitalization Rate of Communicable Diseases in Children

Background

During the 2009 H1N1 pandemic the Danish National board of Health carried out massive public hygiene campaigns to limit spread of disease. We aimed to investigate whether this resulted in lower incidences of communicable diseases in the paediatric population.

Methods

The study compared annual hospitalization rates for childhood infections from 2005 to 2011.

Results

Admission rates for infections were higher during the year of the pandemic compared to the rest of the period.

Conclusion

There were no indications of a preventive effect by the hygiene campaign on incidence of severe common childhood infections.     

Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

Background

Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified.

Results

To search for such proteins, 23 nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells.

Conclusions

The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.     

Adverse Events of Pirfenidone for the Treatment of Pulmonary Fibrosis: A Meta-Analysis of Randomized Controlled Trials

Background

Pirfenidone (PFD) is a novel antifibrotic agent approved for patients with pulmonary fibrosis. However, there are concerns regarding toxicity of the drug. In this meta-analysis, we analyzed the adverse events (AEs) of PFD for the treatment of pulmonary fibrosis.

Methods

We performed a systematic search of PubMed, Embase, ClinicalTrials.gov, and Cochrane Central Register of Controlled Trials for trials published between January 1999 and October 2011. Data extracted from literature were analyzed with Review manager 5.0.24.

Results

The results of six randomized controlled trials (1073 participants) revealed that the number of individuals who discontinued PFD therapy was significantly higher than patients receiving placebo. The PFD group had a significantly higher rate of gastrointestinal (nausea, dyspepsia, diarrhea, and anorexia), neurological (dizziness and fatigue), and dermatological (photosensitivity and rash) AEs compared to the placebo group.

Conclusions

PFD used for the treatment of pulmonary fibrosis is not so safe or well-tolerated. Notably, gastrointestinal, neurological and dermatological adverse effects were more common in patients receiving PFD therapy, and therefore appropriate precaution is needed.     

Search Query Data to Monitor Interest in Behavior Change: Application for Public Health

There is a need for effective interventions and policies that target the leading preventable causes of death in the U.S. (e.g., smoking, overweight/obesity, physical inactivity). Such efforts could be aided by the use of publicly available, real-time search query data that illustrate times and locations of high and low public interest in behaviors related to preventable causes of death.

Objectives

This study explored patterns of search query activity for the terms ‘weight’, ‘diet’, ‘fitness’, and ‘smoking’ using Google Insights for Search.

Methods

Search activity for ‘weight’, ‘diet’, ‘fitness’, and ‘smoking’ conducted within the United States via Google between January 4^th, 2004 (first date data was available) and November 28^th, 2011 (date of data download and analysis) were analyzed. Using a generalized linear model, we explored the effects of time (month) on mean relative search volume for all four terms.

Results

Models suggest a significant effect of month on mean search volume for all four terms. Search activity for all four terms was highest in January with observable declines throughout the remainder of the year.

Conclusions

These findings demonstrate discernable temporal patterns of search activity for four areas of behavior change. These findings could be used to inform the timing, location and messaging of interventions, campaigns and policies targeting these behaviors.     

Outbreak of Multi-Drug Resistant Pseudomonas aeruginosa Bloodstream Infection in the Haematology Unit of a South African Academic Hospital

Objective

To describe an outbreak of multi-resistant Pseudomonas aeruginosa bloodstream infections (MRPA-BSI) that occurred in the haematology ward of a tertiary academic hospital in Cape Town, South Africa, and determine risk factors for acquisition of MRPA-BSI.

Methods

The outbreak investigation included a search for additional cases, review of patient records, environmental and staff screening, molecular typing using pulsed-field gel electrophoresis (PFGE) and Multi-locus sequencing (MLST) and a retrospective case-control study.

Results

Ten MRPA-BSI cases occurred in the haematology ward between January 2010 and January 2011. The case fatality rate was 80%. Staff screening specimens were negative for MRPA and an environmental source was not identified. PFGE showed that 9/10 isolates were related. MLST showed that 3 of these 9 isolates belonged to Sequence type (ST) 233 while the unrelated isolate belonged to ST260.

Conclusion

We have described an outbreak of MRPA-BSI occurring over an extended period of time among neutropenic haematology patients. Molecular typing confirms that the outbreak was predominantly due to a single strain. The source of the outbreak was not identified, but the outbreak appears to have been controlled following intensive infection control measures.     

Coping with Breast Cancer: A Meta-Analysis

Objective

The primary aim of this study was to examine the associations between different types of coping and psychological well-being and physical health among women with breast cancer. A second aim was to explore the potential moderating influences of situational and measurement factors on the associations between coping and psychological well-being and physical health.

Methods

On 14 February 2011, a literature search was made for articles published in the PubMed and PsycINFO databases before January 2010. On 5 September 2013, a repeated literature search was made for articles published before May 2013. In the final analyses, 78 studies with 11 948 participants were included.

Results

Efforts to facilitate adaptation to stress, such as Acceptance and Positive Reappraisal, were related to higher well-being and health. Disengagement and avoidance types of coping were associated with lower well-being and health. The analyses indicated that, in several circumstances, coping effectiveness was dependent on cancer stage, treatment, disease duration, and type of coping measure.

Conclusions

Use of coping targeting adjustment and avoiding use of disengagement forms of coping were related to better psychological well-being and physical health. Adaptive strategies and avoiding disengagement forms of coping seemed particularly beneficial for women undergoing treatment.     

All-Arthroscopic versus Mini-Open Repair of Small to Large Sized Rotator Cuff Tears: A Meta-Analysis of Clinical Outcomes

Purpose

The purpose of this study was to compare clinical outcomes of patients with full-thickness small to large sized tears undergoing all-arthroscopic versus mini-open rotator cuff repair.

Method

A literature search for electronic databases and references for eligible studies was conducted through Medline, Embase and Cochrane library between 1969 and 2013.

Results

A total of 12 comparative studies (n = 770 patients) were included. Pooled results showed: there were no differences in function outcome, pain scores, retear rate or the incidence of adhesive capsulitis between all arthroscopic and mini-open repair groups.

Conclusions

There were no differences in outcomes between the arthroscopic and mini-open rotator cuff repair techniques, they should be considered alternative treatment options.

Level of Evidence

Level IV, Meta analysis.     

Radiogenomic mapping of edema/cellular invasion MRI-phenotypes in glioblastoma multiforme

Background

Despite recent discoveries of new molecular targets and pathways, the search for an effective therapy for Glioblastoma Multiforme (GBM) continues. A newly emerged field, radiogenomics, links gene expression profiles with MRI phenotypes. MRI-FLAIR is a noninvasive diagnostic modality and was previously found to correlate with cellular invasion in GBM. Thus, our radiogenomic screen has the potential to reveal novel molecular determinants of invasion. Here, we present the first comprehensive radiogenomic analysis using quantitative MRI volumetrics and large-scale gene- and microRNA expression profiling in GBM.

Methods

Based on The Cancer Genome Atlas (TCGA), discovery and validation sets with gene, microRNA, and quantitative MR-imaging data were created. Top concordant genes and microRNAs correlated with high FLAIR volumes from both sets were further characterized by Kaplan Meier survival statistics, microRNA-gene correlation analyses, and GBM molecular subtype-specific distribution.

Results

The top upregulated gene in both the discovery (4 fold) and validation (11 fold) sets was PERIOSTIN (POSTN). The top downregulated microRNA in both sets was miR-219, which is predicted to bind to POSTN. Kaplan Meier analysis demonstrated that above median expression of POSTN resulted in significantly decreased survival and shorter time to disease progression (P<0.001). High POSTN and low miR-219 expression were significantly associated with the mesenchymal GBM subtype (P<0.0001).

Conclusion

Here, we propose a novel diagnostic method to screen for molecular cancer subtypes and genomic correlates of cellular invasion. Our findings also have potential therapeutic significance since successful molecular inhibition of invasion will improve therapy and patient survival in GBM.     

Genetic variation in cell death genes and risk of non-Hodgkin lymphoma

Background

Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5^th highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility.

Materials and Methods

We tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate.

Results

Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63–4.82]; p_F = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing.

Conclusions

This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma.     

Prediction of dengue incidence using search query surveillance

Background

The use of internet search data has been demonstrated to be effective at predicting influenza incidence. This approach may be more successful for dengue which has large variation in annual incidence and a more distinctive clinical presentation and mode of transmission.

Methods

We gathered freely-available dengue incidence data from Singapore (weekly incidence, 2004–2011) and Bangkok (monthly incidence, 2004–2011). Internet search data for the same period were downloaded from Google Insights for Search. Search terms were chosen to reflect three categories of dengue-related search: nomenclature, signs/symptoms, and treatment. We compared three models to predict incidence: a step-down linear regression, generalized boosted regression, and negative binomial regression. Logistic regression and Support Vector Machine (SVM) models were used to predict a binary outcome defined by whether dengue incidence exceeded a chosen threshold. Incidence prediction models were assessed using and Pearson correlation between predicted and observed dengue incidence. Logistic and SVM model performance were assessed by the area under the receiver operating characteristic curve. Models were validated using multiple cross-validation techniques.

Results

The linear model selected by AIC step-down was found to be superior to other models considered. In Bangkok, the model has an , and a correlation of 0.869 between fitted and observed. In Singapore, the model has an , and a correlation of 0.931. In both Singapore and Bangkok, SVM models outperformed logistic regression in predicting periods of high incidence. The AUC for the SVM models using the 75th percentile cutoff is 0.906 in Singapore and 0.960 in Bangkok.

Conclusions

Internet search terms predict incidence and periods of large incidence of dengue with high accuracy and may prove useful in areas with underdeveloped surveillance systems. The methods presented here use freely available data and analysis tools and can be readily adapted to other settings.     

Genetic Evidence Implicates the Immune System and Cholesterol Metabolism in the Aetiology of Alzheimer's Disease

Background

Late Onset Alzheimer''s disease (LOAD) is the leading cause of dementia. Recent large genome-wide association studies (GWAS) identified the first strongly supported LOAD susceptibility genes since the discovery of the involvement of APOE in the early 1990s. We have now exploited these GWAS datasets to uncover key LOAD pathophysiological processes.

Methodology

We applied a recently developed tool for mining GWAS data for biologically meaningful information to a LOAD GWAS dataset. The principal findings were then tested in an independent GWAS dataset.

Principal Findings

We found a significant overrepresentation of association signals in pathways related to cholesterol metabolism and the immune response in both of the two largest genome-wide association studies for LOAD.

Significance

Processes related to cholesterol metabolism and the innate immune response have previously been implicated by pathological and epidemiological studies of Alzheimer''s disease, but it has been unclear whether those findings reflected primary aetiological events or consequences of the disease process. Our independent evidence from two large studies now demonstrates that these processes are aetiologically relevant, and suggests that they may be suitable targets for novel and existing therapeutic approaches.     

Mixing Nulliparous and Multiparous Women in Randomised Controlled Trials of Preeclampsia Prevention Is Debatable: Evidence from a Systematic Review

Background

Nulliparity is a major risk factor of preeclampsia investigated in numerous trials of its prevention.

Objective

We aimed to assess whether these trials considered nulliparity in subject selection or analysis of results.

Search Strategy

01 April 2013 search of MEDLINE via PubMed, EMBASE and the Cochrane Library. 01 April 2013 search of trials registered in Clinicaltrials.gov.

Selection Criteria

Randomised controlled trials and metaanalyses of preeclampsia prevention with no restriction to period of publication or language. Metaanalyses were selected to fully identify relevant trials.

Data Collection and Analysis

One reader appraised each selected article/registered protocol using a pretested, standardized data abstraction form developed in a pilot test. For each article, he recorded whether both nulliparous and multiparous were included and, in case of mixed populations, whether randomisation was stratified, and whether subgroup analyses had been reported. For registered protocols, he only assessed whether it was planned to include mixed populations.

Main Results

88 randomised controlled trials were identified, representing 83,396 included women. In 58 of the 88 articles identified (65.9%), preeclampsia was the primary outcome. In 31 of these (53.4%), the investigation combined nulliparous and multiparous women; only two reports in 31 (6.5%) stated that randomisation was stratified on parity and only four (12.9%) described a subgroup analysis by parity. Of the 30 registered trials, 20 (66.6%) planned to include both nulliparous and multiparous women.

Conclusion

Parity is largely ignored in randomised controlled trials of preeclampsia prevention, which raises difficulties in interpreting the results.     

The Association of Episiotomy with Obstetric Anal Sphincter Injury–A Population Based Matched Cohort Study

Objectives

To estimate the independent association of episiotomy with obstetric anal sphincter injuries (OASIS) using first a cross-sectional and then a matched pair analysis.

Design

A matched cohort.

Setting

Data was gathered from the Finnish Medical Birth Register from 2004–2011.

Population

All singleton vaginal births (n = 303,758).

Methods

Women resulting matched pairs (n = 63,925) were matched based on baseline risk of OASIS defined based on parity (first or second/subsequent vaginal births), age, birth weight, mode of delivery, prior caesarean section, and length of active second stage of birth.

Results

In cross-sectional analysis episiotomy was associated with a 12% lower incidence of OASIS (adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.80 to 0.98) in first vaginal births and with a 132% increased incidence of OASIS in second or subsequent vaginal births (aOR 2.32, 95% CI 1.77 to 3.03). In matched pair analysis episiotomy was associated with a 23% (aOR 0.77, 95% CI 0.69 to 0.86) lower incidence of OASIS in first vaginal births and a 61% (aOR 1.61, 95% CI 1.14 to 2.29) increased incidence of OASIS in second or subsequent vaginal births compared to women who gave birth without an episiotomy. The matched pair analysis showed a 12.5% and a 31.6% reduction in aORs of OASIS associated with episiotomy, respectively.

Conclusions

A matched pair analysis showed a substantial reduction in the aORs of OASIS with episiotomy, due to confounding by indication. This indicates that results of observational studies evaluating an association between episiotomy and OASIS should be interpreted with caution.     

A Systematic Literature Search on Psychological First Aid: Lack of Evidence to Develop Guidelines

Background

Providing psychological first aid (PFA) is generally considered to be an important element in preliminary care of disaster victims. Using the best available scientific basis for courses and educational materials, the Belgian Red Cross-Flanders wants to ensure that its volunteers are trained in the best way possible.

Objective

To identify effective PFA practices, by systematically reviewing the evidence in existing guidelines, systematic reviews and individual studies.

Methods

Systematic literature searches in five bibliographic databases (MEDLINE, PsycINFO, The Cochrane Library, PILOTS and G-I-N) were conducted from inception to July 2013.

Results

Five practice guidelines were included which were found to vary in the development process (AGREE II score 20–53%) and evidence base used. None of them provides solid evidence concerning the effectiveness of PFA practices. Additionally, two systematic reviews of PFA were found, both noting a lack of studies on PFA. A complementary search for individual studies, using a more sensitive search strategy, identified 11 237 references of which 102 were included for further full-text examination, none of which ultimately provides solid evidence concerning the effectiveness of PFA practices.

Conclusion

The scientific literature on psychological first aid available to date, does not provide any evidence about the effectiveness of PFA interventions. Currently it is impossible to make evidence-based guidelines about which practices in psychosocial support are most effective to help disaster and trauma victims.