Apparent temperature and cause-specific emergency hospital admissions in Greater Copenhagen, Denmark

One of the key climate change factors, temperature, has potentially grave implications for human health. We report the first attempt to investigate the association between the daily 3-hour maximum apparent temperature (Tapp(max)) and respiratory (RD), cardiovascular (CVD), and cerebrovascular (CBD) emergency hospital admissions in Copenhagen, controlling for air pollution. The study period covered 1 January 2002-31 December 2006, stratified in warm and cold periods. A case-crossover design was applied. Susceptibility (effect modification) by age, sex, and socio-economic status was investigated. For an IQR (8°C) increase in the 5-day cumulative average of Tapp(max), a 7% (95% CI: 1%, 13%) increase in the RD admission rate was observed in the warm period whereas an inverse association was found with CVD (-8%, 95% CI: -13%, -4%), and none with CBD. There was no association between the 5-day cumulative average of Tapp(max) during the cold period and any of the cause-specific admissions, except in some susceptible groups: a negative association for RD in the oldest age group and a positive association for CVD in men and the second highest SES group. In conclusion, an increase in Tapp(max) is associated with a slight increase in RD and decrease in CVD admissions during the warmer months.     

Gate Length Variation Effect on Performance of Gate-First Self-Aligned In0.53Ga0.47As MOSFET

A multi-gate n-type In_0.53Ga_0.47As MOSFET is fabricated using gate-first self-aligned method and air-bridge technology. The devices with different gate lengths were fabricated with the Al₂O₃ oxide layer with the thickness of 8 nm. In this letter, impact of gate length variation on device parameter such as threshold voltage, high and low voltage transconductance, subthreshold swing and off current are investigated at room temperature. Scaling the gate length revealed good enhancement in all investigated parameters but the negative shift in threshold voltage was observed for shorter gate lengths. The high drain current of 1.13 A/mm and maximum extrinsic transconductance of 678 mS/mm with the field effect mobility of 364 cm²/Vs are achieved for the gate length and width of 0.2 µm and 30µm, respectively. The source/drain overlap length for the device is approximately extracted about 51 nm with the leakage current in order of 10⁻⁸ A. The results of RF measurement for cut-off and maximum oscillation frequency for devices with different gate lengths are compared.     

Sporadic Colorectal Cancer Development Shows Rejuvenescence Regarding Epithelial Proliferation and Apoptosis

Background and Aims

Sporadic colorectal cancer (CRC) development is a sequential process showing age-dependency, uncontrolled epithelial proliferation and decreased apoptosis. During juvenile growth cellular proliferation and apoptosis are well balanced, which may be perturbed upon aging. Our aim was to correlate proliferative and apoptotic activities in aging human colonic epithelium and colorectal cancer. We also tested the underlying molecular biology concerning the proliferation- and apoptosis-regulating gene expression alterations.

Materials and Methods

Colorectal biopsies from healthy children (n₁ = 14), healthy adults (n₂ = 10), adult adenomas (n₃ = 10) and CRCs (n₄ = 10) in adults were tested for Ki-67 immunohistochemistry and TUNEL apoptosis assay. Mitosis- and apoptosis-related gene expression was also studied in healthy children (n₁ = 6), adult (n₂ = 41) samples and in CRC (n₃ = 34) in HGU133plus2.0 microarray platform. Measured alterations were confirmed with RT-PCR both on dependent and independent sample sets (n₁ = 6, n₂ = 6, n₃ = 6).

Results

Mitotic index (MI) was significantly higher (p<0.05) in intact juvenile (MI = 0.33±0.06) and CRC samples (MI = 0.42±0.10) compared to healthy adult samples (MI = 0.15±0.06). In contrast, apoptotic index (AI) was decreased in children (0.13±0.06) and significantly lower in cancer (0.06±0.03) compared to healthy adult samples (0.17±0.05). Eight proliferation- (e.g. MKI67, CCNE1) and 11 apoptosis-associated genes (e.g. TNFSF10, IFI6) had altered mRNA expression both in the course of normal aging and carcinogenesis, mainly inducing proliferation and reducing apoptosis compared to healthy adults. Eight proliferation-associated genes including CCND1, CDK1, CDK6 and 26 apoptosis-regulating genes (e.g. SOCS3) were differently expressed between juvenile and cancer groups mostly supporting the pronounced cell growth in CRC.

Conclusion

Colorectal samples from children and CRC patients can be characterized by similarly increased proliferative and decreased apoptotic activities compared to healthy colonic samples from adults. Therefore, cell kinetic alterations during colorectal cancer development show uncontrolled rejuvenescence as opposed to the controlled cell growth in juvenile colonic epithelium.     

Short-term transformation of matrix into hospitable habitat facilitates gene flow and mitigates fragmentation

Habitat fragmentation has major implications for demography and genetic structure of natural plant and animal populations as small and isolated populations are more prone to extinction. Therefore, many recent studies focus on spatial fragmentation. However, the temporal configuration of suitable habitat may also influence dispersal and gene flow in fragmented landscapes. We hypothesize that short-term switching of inhospitable matrix areas into suitable habitat can mitigate effects of spatial fragmentation in natural and seminatural ecosystems. To test our hypothesis, we investigated the hairy-footed gerbil (Gerbillurus paeba, Smith 1836), a ground-dwelling rodent, in fragmented Kalahari savannah areas. Here, rare events of high above mean annual rainfall suggest short-term matrix suitability. During the field survey in 'matrix' areas in the Kalahari (shrub encroachment by heavy grazing) we never observed the hairy-footed gerbil in years of average rainfall, but observed mass occurrences of this species during rare events of exceptionally high rainfall. In a second step, we developed an agent-based model simulating subpopulations in two neighbouring habitats and the separating matrix. Our mechanistic model reproduces the mass occurrences as observed in the field and thus suggests the possibly underlying processes. In particular, the temporary improvement in matrix quality allows reproduction in the matrix, thereby causing a substantial increase in population size. The model demonstrates further how the environmental trigger (rainfall) impacts genetic connectivity of two separated subpopulations. We identified seasonality as a driver of fragmentation but stochasticity leading to higher connectivity. We found that our concept of temporal fragmentation can be applied to numerous other fragmented populations in various ecological systems and provide examples from recent literature. We conclude that temporal aspects of fragmentation must be considered in both ecological research and conservation management.     

Detection of Methylated Septin 9 in Tissue and Plasma of Colorectal Patients with Neoplasia and the Relationship to the Amount of Circulating Cell-Free DNA

Background

Determination of methylated Septin 9 (mSEPT9) in plasma has been shown to be a sensitive and specific biomarker for colorectal cancer (CRC). However, the relationship between methylated DNA in plasma and colon tissue of the same subjects has not been reported.

Methods

Plasma and matching biopsy samples were collected from 24 patients with no evidence of disease (NED), 26 patients with adenoma and 34 patients with CRC. Following bisulfite conversion of DNA a commercial RT-PCR assay was used to determine the total amount of DNA in each sample and the fraction of mSEPT9 DNA. The Septin-9 protein was assessed using immunohistochemistry.

Results

The percent of methylated reference (PMR) values for SEPT9 above a PMR threshold of 1% were detected in 4.2% (1/24) of NED, 100% (26/26) of adenoma and 97.1% (33/34) of CRC tissues. PMR differences between NED vs. adenoma and NED vs. CRC comparisons were significant (p<0.001). In matching plasma samples using a PMR cut-off level of 0.01%, SEPT9 methylation was 8.3% (2/24) of NED, 30.8% (8/26) of adenoma and 88.2% (30/34) of CRC. Significant PMR differences were observed between NED vs. CRC (p<0.01) and adenoma vs. CRC (p<0.01). Significant differences (p<0.01) were found in the amount of cfDNA (circulating cell-free DNA) between NED and CRC, and a modest correlation was observed between mSEPT9 concentration and cfDNA of cancer (R² = 0.48). The level of Septin-9 protein in tissues was inversely correlated to mSEPT9 levels with abundant expression in normals, and diminished expression in adenomas and tumors.

Conclusions

Methylated SEPT9 was detected in all tissue samples. In plasma samples, elevated mSEPT9 values were detected in CRC, but not in adenomas. Tissue levels of mSEPT9 alone are not sufficient to predict mSEPT9 levels in plasma. Additional parameters including the amount of cfDNA in plasma appear to also play a role.     

Individual exposure to NO2 in relation to spatial and temporal exposure indices in Stockholm, Sweden: the INDEX study

Epidemiology studies of health effects from air pollution, as well as impact assessments, typically rely on ambient monitoring data or modelled residential levels. The relationship between these and personal exposure is not clear. To investigate personal exposure to NO(2) and its relationship with other exposure metrics and time-activity patterns in a randomly selected sample of healthy working adults (20-59 years) living and working in Stockholm. Personal exposure to NO(2) was measured with diffusive samplers in sample of 247 individuals. The 7-day average personal exposure was 14.3 μg/m(3) and 12.5 μg/m(3) for the study population and the inhabitants of Stockholm County, respectively. The personal exposure was significantly lower than the urban background level (20.3 μg/m(3)). In the univariate analyses the most influential determinants of individual exposure were long-term high-resolution dispersion-modelled levels of NO(2) outdoors at home and work, and concurrent NO(2) levels measured at a rural location, difference between those measured at an urban background and rural location and difference between those measured in busy street and at an urban background location, explaining 20, 16, 1, 2 and 4% (R(2)) of the 7-day personal NO(2) variation, respectively. A regression model including these variables explained 38% of the variation in personal NO(2) exposure. We found a small improvement by adding time-activity variables to the latter model (R(2)?=?0.44). The results adds credibility primarily to long-term epidemiology studies that utilise long-term indices of NO(2) exposure at home or work, but also indicates that such studies may still suffer from exposure misclassification and dilution of any true effects. In contrast, urban background levels of NO(2) are poorly related to individual exposure.     

Systematic review of economic evaluations of preparedness strategies and interventions against influenza pandemics

Background

Although public health guidelines have implications for resource allocation, these issues were not explicitly considered in previous WHO pandemic preparedness and response guidance. In order to ensure a thorough and informed revision of this guidance following the H1N1 2009 pandemic, a systematic review of published and unpublished economic evaluations of preparedness strategies and interventions against influenza pandemics was conducted.

Methods

The search was performed in September 2011 using 10 electronic databases, 2 internet search engines, reference list screening, cited reference searching, and direct communication with relevant authors. Full and partial economic evaluations considering both costs and outcomes were included. Conversely, reviews, editorials, and studies on economic impact or complications were excluded. Studies were selected by 2 independent reviewers.

Results

44 studies were included. Although most complied with the cost effectiveness guidelines, the quality of evidence was limited. However, the data sources used were of higher quality in economic evaluations conducted after the 2009 H1N1 pandemic. Vaccination and drug regimens were varied. Pharmaceutical plus non-pharmaceutical interventions are relatively cost effective in comparison to vaccines and/or antivirals alone. Pharmaceutical interventions vary from cost saving to high cost effectiveness ratios. According to ceiling thresholds (Gross National Income per capita), the reduction of non-essential contacts and the use of pharmaceutical prophylaxis plus the closure of schools are amongst the cost effective strategies for all countries. However, quarantine for household contacts is not cost effective even for low and middle income countries.

Conclusion

The available evidence is generally inconclusive regarding the cost effectiveness of preparedness strategies and interventions against influenza pandemics. Studies on their effectiveness and cost effectiveness should be readily implemented in forthcoming events that also involve the developing world. Guidelines for assessing the impact of disease and interventions should be drawn up to facilitate these studies.