In vivo-induced size transformation of cerium oxide nanoparticles in both lung and liver does not affect long-term hepatic accumulation following pulmonary exposure.
Recent findings show that cerium oxide (CeO2) nanoparticles may undergo in vivo-induced size transformation with the formation of smaller particles that could result in a higher translocation following pulmonary exposure compared to virtually insoluble particles, like titanium dioxide (TiO2). Therefore, we compared liver deposition of CeO2 and TiO2 nanoparticles of similar primary sizes 1, 28 or 180 days after intratracheal instillation of 162 μg of NPs in female C57BL/6 mice. Mice exposed to 162 μg CeO2 or TiO2 nanoparticles by intravenous injection or oral gavage were included as reference groups to assess the amount of NPs that reach the liver bypassing the lungs and the translocation of NPs from the gastrointestinal tract to the liver, respectively. Pulmonary deposited CeO2 nanoparticles were detected in the liver 28 and 180 days post-exposure and TiO2 nanoparticles 180 days post-exposure as determined by darkfield imaging and by the quantification of Ce and Ti mass concentration by inductively coupled plasma-mass spectrometry (ICP-MS). Ce and Ti concentrations increased over time and 180 days post-exposure the translocation to the liver was 2.87 ± 3.37% and 1.24 ± 1.98% of the initial pulmonary dose, respectively. Single particle ICP-MS showed that the size of CeO2 nanoparticles in both lung and liver tissue decreased over time. No nanoparticles were detected in the liver following oral gavage. Our results suggest that pulmonary deposited CeO2 and TiO2 nanoparticles translocate to the liver with similar calculated translocation rates despite their different chemical composition and shape. The observed particle size distributions of CeO2 nanoparticles indicate in vivo processing over time both in lung and liver. The fact that no particles were detected in the liver following oral exposure showed that direct translocation of nanoparticles from lung to the systemic circulation was the most important route of translocation for pulmonary deposited particles.


Local Tandem Repeat Expansion in Xist RNA as a Model for the Functionalisation of ncRNA.
Xist, the master regulator of the X chromosome inactivation in mammals, is a 17 kb lncRNA that acts in cis to silence the majority of genes along the chromosome from which it is transcribed. The two key processes required for Xist RNA function, localisation in cis and recruitment of silencing factors, are genetically separable, at least in part. Recent studies have identified Xist RNA sequences and associated RNA-binding proteins (RBPs) that are important for these processes. Notably, several of the key Xist RNA elements correspond to local tandem repeats. In this review, I use examples to illustrate different modes whereby tandem repeat amplification has been exploited to allow orthodox RBPs to confer new functions for Xist-mediated chromosome inactivation. I further discuss the potential generality of tandem repeat expansion in the evolution of functional long non-coding RNAs (lncRNAs).


The bioelements, the elementome, and the biogeochemical niche.
Every living creature on Earth is made of atoms of the various bioelements that are harnessed in the construction of molecules, tissues, organisms, and communities, as we know them. Organisms need these bioelements in specific quantities and proportions to survive and grow. Distinct species have different functions and life strategies, and have therefore developed distinct structures and adopted a certain combination of metabolic and physiological processes. Each species is thus also expected to have different requirements for each bioelement. We therefore propose that a "biogeochemical niche" can be associated with the classical ecological niche of each species. We show from field data examples that a biogeochemical niche is characterized by a particular elementome defined as the content of all (or at least most) bioelements. The differences in elementome among species are a function of taxonomy and phylogenetic distance, sympatry (the bioelemental compositions should differ more among coexisting than among non-coexisting species to avoid competitive pressure), and homeostasis with a continuum between high homeostasis/low plasticity and low homeostasis/high plasticity. This proposed biogeochemical niche hypothesis has the advantage relative to other associated theoretical niche hypotheses that it can be easily characterized by actual quantification of a measurable trait: the elementome of a given organism or a community, being potentially applicable across taxa and habitats. The changes in bioelemental availability can determine genotypic selection and therefore have a feedback on ecosystem function and organization, and, at the end, become another driving factor of the evolution of life and the environment.


Perception of the Quality of Communication With Physicians Among Relatives of Dying Residents of Long-term Care Facilities in 6 European Countries: PACE Cross-Sectional Study.
To examine how relatives evaluate the quality of communication with the treating physician of a dying resident in long-term care facilities (LTCFs) and to assess its differences between countries. A cross-sectional retrospective study in a representative sample of LTCFs conducted in 2015. Relatives of residents who died during the previous 3 months were sent a questionnaire. 761 relatives of deceased residents in 241 LTCFs in Belgium, England, Finland, Italy, the Netherlands, and Poland. The Family Perception of Physician-Family Communication (FPPFC) scale (ratings from 0 to 3, where 3 means the highest quality) was used to retrospectively assess how the quality of end-of-life communication with treating physicians was perceived by relatives. We applied multilevel linear and logistic regression models to assess differences between countries and LTCF types. The FPPFC score was the lowest in Finland (1.4 ± 0.8) and the highest in Italy (2.2 ± 0.7). In LTCFs served by general practitioners, the FPPFC score differed between countries, but did not in LTCFs with on-site physicians. Most relatives reported that they were well informed about a resident's general condition (from 50.8% in Finland to 90.6% in Italy) and felt listened to (from 53.1% in Finland to 84.9% in Italy) and understood by the physician (from 56.7% in Finland to 85.8% in Italy). In most countries, relatives assessed the worst communication as being about the resident's wishes for medical treatment at the end of life, with the lowest rate of satisfied relatives in Finland (37.6%). The relatives' perception of the quality of end-of-life communication with physicians differs between countries. However, in all countries, physicians' communication needs to be improved, especially regarding resident's wishes for medical care at the end of life. Training in end-of-life communication to physicians providing care for LTCF residents is recommended.


Immune-Mediated Repair: A Matter of Plasticity.
Though the immune system is generally defined as a system of defense, it is increasingly recognized that the immune system also plays a crucial role in tissue repair and its potential dysregulations. In this review, we explore how distinct immune cell types are involved in tissue repair and how they interact in a process that is tightly regulated both spatially and temporally. We insist on the concept of immune cell plasticity which, in recent years, has proved fundamental for the success/understanding of the repair process. Overall, the perspective presented here suggests that the immune system plays a central role in the physiological robustness of the organism, and that cell plasticity contributes to the realization of this robustness.


Femoroacetabular impingement.
Femoroacetabular impingement (FAI) is a pathomechanical concept describing the early and painful contact of morphological changes of the hip joint, both on the acetabular, and femoral head sides. These can lead clinically to symptoms of hip and groin pain, and a limited range of motion with labral, chondral and bony lesions. Pincer impingement generally involves the acetabular side of the joint where there is excessive coverage of the acetabulum, which may be focal or more diffuse. There is linear contact of the acetabulum with the head/neck junction. Cam impingement involves the femoral head side of the joint where the head is associated with bony excrescences and is aspheric. The aspheric femoral head jams into the acetabulum. Imaging appearances are reviewed below. This type is evident in young males in the second and third decades. The main features of FAI are described.


Repeated sleep disruption in mice leads to persistent shifts in the fecal microbiome and metabolome.
It has been established in recent years that the gut microbiome plays a role in health and disease, potentially via alterations in metabolites that influence host physiology. Although sleep disruption and gut dysbiosis have been associated with many of the same diseases, studies investigating the gut microbiome in the context of sleep disruption have yielded inconsistent results, and have not assessed the fecal metabolome. We exposed mice to five days of sleep disruption followed by four days of ad libitum recovery sleep, and assessed the fecal microbiome and fecal metabolome at multiple timepoints using 16S rRNA gene amplicons and untargeted LC-MS/MS mass spectrometry. We found global shifts in both the microbiome and metabolome in the sleep-disrupted group on the second day of recovery sleep, when most sleep parameters had recovered to baseline levels. We observed an increase in the Firmicutes:Bacteroidetes ratio, along with decreases in the genus Lactobacillus, phylum Actinobacteria, and genus Bifidobacterium in sleep-disrupted mice compared to control mice. The latter two taxa remained low at the fourth day post-sleep disruption. We also identified multiple classes of fecal metabolites that were differentially abundant in sleep-disrupted mice, some of which are physiologically relevant and commonly influenced by the microbiome. This included bile acids, and inference of microbial functional gene content suggested reduced levels of the microbial bile salt hydrolase gene in sleep-disrupted mice. Overall, this study adds to the evidence base linking disrupted sleep to the gut microbiome and expands it to the fecal metabolome, identifying sleep disruption-sensitive bacterial taxa and classes of metabolites that may serve as therapeutic targets to improve health after poor sleep.


Office-based motivational interviewing to prevent childhood obesity: a feasibility study.
To determine whether pediatricians and dietitians can implement an office-based obesity prevention program using motivational interviewing as the primary intervention. Nonrandomized clinical trial. Fifteen pediatricians belonging to Pediatric Research in Office Settings, a national practice-based research network, and 5 registered dietitians were assigned to 1 of 3 groups: (1) control; (2) minimal intervention (pediatrician only); or (3) intensive intervention (pediatrician and registered dietitian). Primary care pediatric offices. Ninety-one children presenting for well-child care visits met eligibility criteria of being aged 3 to 7 years and having a body mass index (calculated as the weight in kilograms divided by the height in meters squared) at the 85th percentile or greater but lower than the 95th percentile for the age or having a normal weight and a parent with a body mass index of 30 or greater. Pediatricians and registered dietitians in the intervention groups received motivational interviewing training. Parents of children in the minimal intervention group received 1 motivational interviewing session from the physician, and parents of children in the intensive intervention group received 2 motivational interviewing sessions each from the pediatrician and the registered dietitian. Change in the body mass index-for-age percentile. At 6 months' follow-up, there was a decrease of 0.6, 1.9, and 2.6 body mass index percentiles in the control, minimal, and intensive groups, respectively. The differences in body mass index percentile change between the 3 groups were nonsignificant (P=.85). The patient dropout rates were 2 (10%), 13 (32%), and 15 (50%) for the control, minimal, and intensive groups, respectively. Fifteen (94%) of the parents reported that the intervention helped them think about changing their family's eating habits. Motivational interviewing by pediatricians and dietitians is a promising office-based strategy for preventing childhood obesity. However, additional studies are needed to demonstrate the efficacy of this intervention in practice settings.


Effects of rotigotine on daytime symptoms in patients with primary restless legs syndrome: a randomized, placebo-controlled study.
This 12 week double-blind, placebo-controlled study (ClinicalTrials.gov: NCT01569464) was conducted to evaluate the effects of rotigotine transdermal patch on daytime symptoms in patients with idiopathic restless legs syndrome (RLS). Adult patients with moderate-to-severe RLS were randomized to rotigotine (optimal dose: 1-3 mg/24 h) or placebo. A modified four-assessment version (4:00 pm, 6:00 pm, 8:00 pm, and 10:00 pm) of the Multiple Suggested Immobilization Test (m-SIT) was performed at baseline and end of 4 week maintenance (EoM). Primary study outcomes were change from baseline to EoM in International Restless Legs Syndrome Rating Scale (IRLS) and in average of means for the m-SIT Discomfort Scale (m-SIT-DS) (combined average of mean values from each of the individual assessments). Secondary outcomes included average of means of Periodic Limb Movement during Wakefulness Index (PLMWI; PLM/hour) for the combination of m-SIT. A total of 150 patients were randomized and 137 (rotigotine: 92/101 [91.1%]; placebo: 45/49 [91.8%]) completed maintenance. All 150 randomized patients were assessed for efficacy. At EoM, mean change in IRLS was -14.9 ± 9.3 with rotigotine vs. -12.7 ± 7.6 with placebo (ANCOVA, LS mean treatment difference [95% CI]: -0.27 [-2.96, 2.42]; p = 0.8451). Changes in average of means of m-SIT-DS values of each individual SIT were comparable with rotigotine (-2.68 ± 2.31) vs. placebo (-2.62 ± 2.61) (ANCOVA, LS mean treatment difference [95% CI]: 0.07 [-0.61, 0.75]; p = 0.8336) and comparable reductions in PLMWI were observed in both treatment groups (8.34 [-8.50, 25.17]; p = 0.3290). Rotigotine was generally well tolerated. Application site reactions (rotigotine: 20 patients [19.8%]; placebo: 4 [8.2%]) and nausea (16 [15.8%]; 3 [6.1%]) were the most common AEs. Rotigotine was beneficial in improving overall RLS symptom severity (assessed by IRLS) and RLS symptom severity at various times of the day (m-SIT-DS); however, superiority to placebo was not established.


Application of high-speed counter-current chromatography combined with macroporous resin for rapid enrichment and separation of three anthraquinone glycosides and one stilbene glycoside from Rheum tanguticum.
In this paper, an efficient method was successfully established by the combination of macroporous resin (MR) and high-speed counter-current chromatography (HSCCC) for rapid enrichment and separation of aloe-emodin 8-O-β-D-glucoside, emodin 1-O-β-D-glucoside, emodin 8-O-β-D-glucoside and piceatannol 4'-O-β-D-(6″-O-gallate)-glucoside. Six kinds of macroporous resins were investigated in the first step and X-5 macroporous resin was selected for the enrichment of the target compounds. The recoveries of the target compounds reached 89.0, 85.9, 82.3 and 84.9% respectively after 40% ethanol elution. In the second step, the target compounds were separated by HSCCC with a two-phase solvent system composed of chloroform/ethyl acetate/methanol/water (8:1:6:5, v/v). The established method will be helpful for further characterization and utilization of Rheum tanguticum. The results demonstrate that MR coupled with HSCCC is a powerful technique for separation of bioactive compounds from natural products.


Neurocognitive subgroups in major depressive disorder.
Major depressive disorder (MDD) is commonly associated with neurocognitive dysfunction. However, there remains substantial heterogeneity between patients and inconsistent findings regarding the magnitude and prevalence of specific neurocognitive deficits. This study aimed to investigate the potential for different neurocognitive subgroups in patients diagnosed with MDD. Data were pooled from 4 different clinical trials that involved adults diagnosed with MDD. Neurocognitive outcomes included measures of verbal learning and memory, executive function, attention, and processing speed. Latent class analysis was conducted to examine for different subgroups based on neurocognitive profiles of performance across outcome measures. Subgroups were compared to a separate sample of age-matched adult healthy controls, across illness factors, and individual mood items on the Montgomery-Åsberg Depression Rating Scale (MADRS). Within the MDD cohort (N = 149), 45% of participants were considered relatively "cognitively preserved," with the remainder "cognitively reduced" (39%) or "cognitively impaired" (16%). Verbal memory performance was significantly poorer compared to attention and processing speed only in the "cognitively impaired" subgroup. There was no association between subgroup membership and relevant illness factors, including ratings on individual MADRS items. Data were pooled from several studies that included different neurocognitive measures and cohorts. Approximately half of MDD participants had no or minimal objective cognitive difficulties, and neurocognitive functioning was found generally unrelated to illness factors. Future longitudinal research is warranted to determine whether the people who are relatively cognitively impaired are at increased risk for further cognitive decline. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


In vitro effects of acetylcholinesterase inhibitors and reactivators on Complex I of electron transport chain.
Inhibition of the enzyme acetylcholinesterase (AChE) is the main mechanism both of therapeutic action of drugs for the treatment of Alzheimer's disease and toxic action of organophosphorus compounds. Various types of oximes reactivate AChE and are commonly used as antidotes against organophosphates (pesticides, nerve agents). Effects both of AChE inhibitors (tacrine, 7-methoxytacrine) and oximes (pralidoxime, trimedoxime, obidoxime, methoxime, HI-6) on Complex I of electron transport chain (ETC) were examined. The enzyme activity was measured spectrophotometrically in crude mitochondrial fraction isolated from pig brain. Our results showed statistically significant Complex I inhibition by tacrine, other drugs did not affect the enzyme activity significantly. These observations suggest the possibility of tacrine-induced side effects related to disturbance in ETC. On the contrary, it seems that oximes do not affect cellular energetic metabolism.


Mammalian autophagy degrades nuclear constituents in response to tumorigenic stress.
During autophagy, double-membrane autophagosomes are observed in the cytoplasm. Thus, extensive studies have focused on autophagic turnover of cytoplasmic material. Whether autophagy has a role in degrading nuclear constituents is poorly understood. We reveal that the autophagy protein LC3/Atg8 directly interacts with the nuclear lamina protein LMNB1 (lamin B1), and binds to LMN/lamin-associated chromatin domains (LADs). Through these interactions, autophagy specifically mediates destruction of nuclear lamina during tumorigenic stress, such as by activated oncogenes and DNA damage. This nuclear lamina degradation upon aberrant cellular stress impairs cell proliferation by inducing cellular senescence, a stable form of cell-cycle arrest and a tumor-suppressive mechanism. Our findings thus suggest that, in response to cancer-promoting stress, autophagy degrades nuclear material to drive cellular senescence, as a means to restrain tumorigenesis. Our work provokes a new direction in studying the role of autophagy in the nucleus and in tumor suppression.


Two-part payments for the reimbursement of investments in health technologies.
The paper studies the impact of alternative reimbursement systems on two provider decisions: whether to adopt a technology whose provision requires a sunk investment cost and how many patients to treat with it. Using a simple economic model we show that the optimal pricing policy involves a two-part payment: a price equal to the marginal cost of the patient whose benefit of treatment equals the cost of provision, and a separate payment for the partial reimbursement of capital costs. Departures from this scheme, which are frequent in DRG tariff systems designed around the world, lead to a trade-off between the objective of making effective technologies available to patients and the need to ensure appropriateness in use.


Development of a digital-micromirror-device-based multishot snapshot spectral imaging system.
We report on the development of a digital-micromirror-device (DMD)-based multishot snapshot spectral imaging (DMD-SSI) system as an alternative to current piezostage-based multishot coded aperture snapshot spectral imager (CASSI) systems. In this system, a DMD is used to implement compressive sensing (CS) measurement patterns for reconstructing the spatial/spectral information of an imaging scene. Based on the CS measurement results, we demonstrated the concurrent reconstruction of 24 spectral images. The DMD-SSI system is versatile in nature as it can be used to implement independent CS measurement patterns in addition to spatially shifted patterns that piezostage-based systems can offer.


Three Novel Species with Peptidoglycan Cell Walls form the New Genus Lacunisphaera gen. nov. in the Family Opitutaceae of the Verrucomicrobial Subdivision 4.
The cell wall of free-living bacteria consists of peptidoglycan (PG) and is critical for maintenance of shape as dissolved solutes cause osmotic pressure and challenge cell integrity. Surprisingly, the subdivision 4 of the phylum Verrucomicrobia appears to be exceptional in this respect. Organisms of this subdivision are described to be devoid of muramic or diaminopimelic acid (DAP), usually found as components of PG in bacterial cell walls. Here we describe three novel bacterial strains from a freshwater lake, IG15T, IG16bT, and IG31T, belonging to a new genus in the subdivision 4 of Verrucomicrobia which we found to possess PG as part of their cell walls. Biochemical analysis revealed the presence of DAP not only in these novel strains, but also in Opitutus terrae PB90-1T, the closest described relative of strains IG15T, IG16bT, and IG31T. Furthermore, we found that nearly all genes necessary for peptidoglycan synthesis are present in genomes of subdivision 4 members, as well as in the complete genome sequence of strain IG16bT. In addition, we isolated and visualized PG-sacculi for strain IG16bT. Thus, our results challenge the concept of peptidoglycan-less free-living bacteria. Our polyphasic taxonomy approach places the novel strains in a new genus within the family Opitutaceae, for which the name Lacunisphaera gen. nov. is proposed. Strain designations for IG15T, IG16bT and IG31T are Lacunisphaera parvula sp. nov. (=DSM 26814 = LMG 29468), L. limnophila sp. nov. (=DSM 26815 = LMG 29469) and L. anatis sp. nov. (=DSM 103142 = LMG 29578) respectively, with L. limnophila IG16bT being the type species of the genus.


Gaps in care for patients with memory deficits after stroke: views of healthcare providers.
Stroke is a common cause of physical disability but is also strongly associated with cognitive impairment and a risk for future dementia. Despite national clinical guidelines, the service provided for stroke survivors with cognitive and memory difficulties varies across localities. This study critically evaluated the views of healthcare professionals about barriers and facilitators to their care. Seventeen semi-structured individual interviews were conducted by a single interviewer with both primary and secondary care clinicians in regular contact with stroke-survivors. This included stroke medicine specialists, specialist nurses, physiotherapists, occupational therapists, general practitioners and primary care nurses. Topics included individual experiences of the current care offered to patients with cognitive impairment, assessment processes and inter-professional communication. Interviews were audio recorded and transcribed verbatim. Transcripts were thematically analysed and themes grouped into broad categories to facilitate interpretation. Data analysis identified four key themes as barriers to optimal care for stroke-survivors with memory difficulties: 1) Less focus on memory and cognition in post-stroke care; 2) Difficulties bringing up memory and cognitive problems post-stroke; 3) Lack of clarity in current services; and, 4) Assumptions made by healthcare professionals introducing gaps in care. Facilitators included stronger links between primary and secondary care in addition to information provision at all stages of care. The care provided by stroke services is dominated by physical impairments. Clinicians are unsure who should take responsibility for follow-up of patients with cognitive problems. This is made even more difficult by the lack of experience in assessment and stigma surrounding potential diagnoses associated with these deficits. Service development should focus on increased cohesiveness between hospital and community care to create a clear care pathway for post-stroke cognitive impairment.


Small cell lung cancer: radionuclide bone scans for assessment of tumor extent and response.
Radionuclide bone scans were performed before and during combination chemotherapy in 119 systematically staged patients with small cell carcinoma of the lung. Before therapy, 49 patients (41%) had positive scans. Scan positivity was significantly associated with the presence of metastatic tumor in the bone marrow, positive skeletal radiographs, and elevated serum alkaline phosphatase levels. Nonosseous distant metastases were significantly more likely to be detected as the number of areas of focal abnormalities on bone scan increased. The survival of patients with documented distant metastases in bone and nonosseous sites was significantly inferior to the survival of patients with limited disease, isolated osseous extensive disease, and extensive disease occurring only in nonbony sites. Of 36 patients with initially abnormal scans and tumor regression documented by other methods, scan findings improved in 24 (67%). In 26 (36%) of 72 scans in patients demonstrating disease progression in extraosseous sites, new areas of increased radionuclide uptake appeared. Improvement or worsening in follow-up scans was associated with nonbony tumor response or progression, respectively, 70% of the time. Serial bone scans provide reasonably accurate staging and prognostic information in patients with small cell lung cancer, although they are probably not sufficiently reliable to be used as the sole parameter in therapeutic decision-making.


Potentiation of a novel palladium (II) complex lethality with bee venom on the human T-cell acute lymphoblastic leukemia cell line (MOLT-4).
Although honeybee venom (BV) has been reported to induce apoptosis in different types of cancerous cells, its synergistic effects with customary anti-cancer drugs remain largely unknown. In the present study, we evaluated the cytotoxic effect of BV alone (as a natural product) and the synergistic cytological effects of this component in combination with [Pd (bpy) (Pi-Pydtc)]NO3 - a novel palladium complex on human T-cell lymphoblastic leukemia cells. To investigate the cytotoxic effect of the BV alone and in combination with palladium complex on MOLT-4 cells MTT assay was performed. In order to determine the apoptotic effects of BV separately and in combination with Pd (II) complex on these cells and its ability to induce apoptosis, morphological examination, flowcytometric analysis and caspase-3 colorimetric assay were done. We found that BV induced morphological changes, namely nuclear shrinkage, and inhibited MOLT-4 cell proliferation; both effects were dose- and time-dependent. Flow cytometry by Annexin-V antibody demonstrated that BV induced apoptosis in MOLT-4 cells. Furthermore, BV induced apoptosis independently of caspase-3 in these cells. In addition, we proved a clear synergistic effect of BV on [Pd (bpy) (Pi-Pydtc)]NO3. The apoptotic pathway activated by BV in combination with Pd complex was caspase-3-dependent. These observations provide an explanation for the anti-proliferative properties of BV, and suggest that this agent may be useful for treating lymphoblastic leukemia alone or in combination with chemotherapy drugs pending further investigations on animal models as preclinical tests.


Texture classification from random features.
Inspired by theories of sparse representation and compressed sensing, this paper presents a simple, novel, yet very powerful approach for texture classification based on random projection, suitable for large texture database applications. At the feature extraction stage, a small set of random features is extracted from local image patches. The random features are embedded into a bag-of-words model to perform texture classification; thus, learning and classification are carried out in a compressed domain. The proposed unconventional random feature extraction is simple, yet by leveraging the sparse nature of texture images, our approach outperforms traditional feature extraction methods which involve careful design and complex steps. We have conducted extensive experiments on each of the CUReT, the Brodatz, and the MSRC databases, comparing the proposed approach to four state-of-the-art texture classification methods: Patch, Patch-MRF, MR8, and LBP. We show that our approach leads to significant improvements in classification accuracy and reductions in feature dimensionality.


Phase variation of a Type IIG restriction-modification enzyme alters site-specific methylation patterns and gene expression in Campylobacter jejuni strain NCTC11168.
Phase-variable restriction-modification systems are a feature of a diverse range of bacterial species. Stochastic, reversible switches in expression of the methyltransferase produces variation in methylation of specific sequences. Phase-variable methylation by both Type I and Type III methyltransferases is associated with altered gene expression and phenotypic variation. One phase-variable gene of Campylobacter jejuni encodes a homologue of an unusual Type IIG restriction-modification system in which the endonuclease and methyltransferase are encoded by a single gene. Using both inhibition of restriction and PacBio-derived methylome analyses of mutants and phase-variants, the cj0031c allele in C. jejuni strain NCTC11168 was demonstrated to specifically methylate adenine in 5'CCCGA and 5'CCTGA sequences. Alterations in the levels of specific transcripts were detected using RNA-Seq in phase-variants and mutants of cj0031c but these changes did not correlate with observed differences in phenotypic behaviour. Alterations in restriction of phage growth were also associated with phase variation (PV) of cj0031c and correlated with presence of sites in the genomes of these phages. We conclude that PV of a Type IIG restriction-modification system causes changes in site-specific methylation patterns and gene expression patterns that may indirectly change adaptive traits.


[Transdermal carbimazole for the treatment of feline hyperthyroidism].
Orally administered antithyroid drugs are frequently used to treat hyperthyroidism in cats; however, the non-cooperative behaviour of some cats may make it difficult to administer tablets. The aim of this study was to develop a carbimazole ointment for application to the inner pinna of the ear and to test its effectiveness in 13 cats with hyperthyroidism. Laboratory investigations were performed before, and 4, 8, and 12 weeks after start of the treatment. Laboratory data for 9 cats were available at the end of the observation period. The starting dose of carbimazole ointment was 5 mg once daily. If no complications occurred, the dose was increased to 5 mg twice daily from the 6th day onwards. Further dose adjustments were mainly based on the plasma thyroxine (T4) concentration. The median plasma T4 concentration at the end of the observation period (24 nmol/l) was significantly lower than that before treatment (152 nmol/l). The dosage of carbimazole needed to achieve euthyroidism ranged from 4 to 17 mg twice daily. Treatment with carbimazole ointment resulted in disappearance of signs of hyperthyroidism; plasma concentrations of urea and creatinine increased significantly. The results of this study indicate that twice daily administration of carbimazole ointment to the inner pinna of the ear is an effective treatment for hyperthyroidism in cats. This provides the veterinarian with a new and promising treatment option. Because carbimazole ointment has not been registered, according to European law it can only be used for the treatment of hyperthyroidism in cats if other licensed medications have been tried and if there is a therapeutic need.


Half a century of molecular bioenergetics.
Molecular bioenergetics deals with the construction, function and regulation of the powerhouses of life. The present overview sketches scenes and actors, farsighted goals and daring hypotheses, meticulous tool-making, painstaking benchwork, lucky discovery, serious scepticism, emphatic believing and strong characters with weak and others with hard arguments, told from a personal, admittedly limited, perspective. Bioenergetics will blossom further with the search focused on both where there is bright light for ever-finer detail and the obvious dark spots for surprise and discovery.


Association network analysis identifies enzymatic components of gut microbiota that significantly differ between colorectal cancer patients and healthy controls.
The human gut microbiota plays a major role in maintaining human health and was recently recognized as a promising target for disease prevention and treatment. Many diseases are traceable to microbiota dysbiosis, implicating altered gut microbial ecosystems, or, in many cases, disrupted microbial enzymes carrying out essential physio-biochemical reactions. Thus, the changes of essential microbial enzyme levels may predict human disorders. With the rapid development of high-throughput sequencing technologies, metagenomics analysis has emerged as an important method to explore the microbial communities in the human body, as well as their functionalities. In this study, we analyzed 156 gut metagenomics samples from patients with colorectal cancer (CRC) and adenoma, as well as that from healthy controls. We estimated the abundance of microbial enzymes using the HMP Unified Metabolic Analysis Network method and identified the differentially abundant enzymes between CRCs and controls. We constructed enzymatic association networks using the extended local similarity analysis algorithm. We identified CRC-associated enzymic changes by analyzing the topological features of the enzymatic association networks, including the clustering coefficient, the betweenness centrality, and the closeness centrality of network nodes. The network topology of enzymatic association network exhibited a difference between the healthy and the CRC environments. The ABC (ATP binding cassette) transporter and small subunit ribosomal protein S19 enzymes, had the highest clustering coefficient in the healthy enzymatic networks. In contrast, the Adenosylhomocysteinase enzyme had the highest clustering coefficient in the CRC enzymatic networks. These enzymic and metabolic differences may serve as risk predictors for CRCs and are worthy of further research.


Differentiation of mesothelioma from adenocarcinoma in serous effusions: the role of hyaluronic acid and CD44 localization.
Differentiating cells of mesothelial origin from adenocarcinoma (ACA) based on morphology alone can be a diagnostic challenge, especially in cytological specimens. Malignant mesothelioma (MM) is characterized by accumulation of abundant intracellular hyaluronic acid (HA), a feature that is not reported in ACA. The purpose of this study was to evaluate the significance of cellular HA using an HA-specific binding peptide (HABP) and the expression of its principal receptor, the standard CD44 molecule (CD44S). Archival paraffin-embedded cell blocks of serous fluids from 28 cases of reactive mesothelial cells, 14 cases of MM, 20 cases of metastatic ovarian carcinomas, 17 cases of metastatic breast carcinomas, 12 cases of metastatic lung ACA, and 12 cases of metastatic gastrointestinal ACA were stained with HA using a biotinylated HABP and CD44S. Positive staining was defined as droplet to diffuse cytoplasmic staining for HA and uniform membranous staining for CD44S. All MMs and 93% (26/28) of the benign mesothelial cells were positive for intracytoplasmic HA vs. none of ACAs. CD44S was expressed in 100% (28/28) of mesothelial hyperplesia, 86% (12/14) of MMs, 70% (14/20) of ovarian carcinomas, 29% (5/17) of breast carcinomas, 25% (3/12) of gastrointestinal ACAs, and 8% (1/12) of lung ACAs. In MM and reactive mesothelial cells, CD44S stained cell membranes diffusely with highlights on the villous surfaces and in ACA it was focal and confined to cell membranes. Immunostaining with HA is a reliable marker that can distinguish between cells of mesothelial origin (reactive mesothelial cells and MM) and ACA. The CD44S staining pattern of cells of mesothelial origin is of diagnostic significance. CD44 may prove useful in conjunction with other stains in the differential diagnosis of mesothelioma and ADA.


Cardioprotection in the Modern Era of Cancer Chemotherapy.
The current arsenal of cancer chemotherapy is broad and rapidly expanding and includes conventional cytotoxic agents and targeted and immune-based therapies. As cancer survival rates have improved, the acute and latent cardiotoxicities of chemotherapy have emerged as important contributors to morbidity and mortality in cancer survivors. All chemotherapeutic agents have the potential for cardiac complications, with manifestations ranging from subclinical left ventricular dysfunction and asymptomatic QT prolongation, to congestive heart failure, myocardial ischemia, myocarditis, arrhythmia, and sudden cardiac death. Efforts are ongoing to identify patients at high risk of cardiac complications and to develop evidence-based approaches to cardioprotection. In this review, we describe antitumor agents commonly associated with cardiotoxicity, with a focus on risk assessment, surveillance strategies, and pharmacologic and nonpharmacologic interventions aimed at preventing and mitigating chemotherapy-induced myocardial dysfunction.


Asthma in adolescence affects daily life and school attendance - Two cross-sectional population-based studies 10 years apart.
The aim of this study was to study the impact of asthma on daily life, school absenteeism and physical education. In addition, to describe asthma triggers at school. Two cross-sectional population-based studies ten years apart. Within the OLIN-studies, in 2003 (n = 3,327) and in 2013 (n = 2,345) adolescents (14-15 years) answered an expanded ISAAC questionnaire. Of these, 8% and 11%, respectively with current asthma participated in this study. Between the years 2003-2013, the proportion of adolescents reporting that asthma interfered with daily life had increased, in 2013, girls were significantly more affected than boys. The proportion reporting a worsening of asthma at school had decreased, but it was still over a quarter. The proportion of absenteeism from school and from physical education was at the same level both years. Asthma triggers were described to be poor air quality, poorly cleaned environment, allergens, strong fragrance, rebuilding projects, physical education and stress.


Murine FGF-12 and FGF-13: expression in embryonic nervous system, connective tissue and heart.
The molecular cloning of cDNAs encoding murine fibroblast growth factor-13 (FGF-13/FHF-2) and three isoforms of murine FGF-12 (FHF-1) is described. Like their highly conserved human counterparts, murine FGF-12 and FGF-13 are part of a distinct subfamily of FGF-like proteins characterized by a greater degree of amino acid sequence cross-homology and by conserved N-terminal domains which do not include secretion signal sequences. In addition to their expression in several adult tissues, both of these FGF genes are prominently and regionally expressed in midgestation mouse embryos, as revealed by in situ hybridization. Fgf12 and fgf13. RNAs were detected in developing central nervous system in cells outside the proliferating ependymal layer, and fgf13 RNA was also found throughout the peripheral nervous system. Fgf12 is expressed in developing soft connective tissue of the limb skeleton and in presumptive connective tissue linking vertebrae and ribs. Both FGF genes are also expressed in the myocardium of the heart, with fgf12 RNA found only in the atrial chamber and fgf13 RNA detected in both atrium and ventricle. On the basis of their novel structure and patterns of expression, FGF-12 and FGF-13 are anticipated to perform embryonic functions distinct from other known FGF molecules.


Autologous transplantation in poor risk Hodgkin's disease using high dose melphalan/etoposide conditioning with non-cryopreserved marrow rescue. The Newcastle and Northern Region Lymphoma Group.
This study aimed to assess the safety and efficacy of using high dose melphalan and etoposide followed by autologous, non-cryopreserved marrow rescue in advanced Hodgkin's disease (HD). Seventeen patients with poor risk Hodgkin's disease from a single centre underwent autologous bone marrow transplant (ABMT) using high dose melphalan and etopside conditioning. Two patients had primary progressive resistant disease (PD), two were in fourth relapse, six in second or third complete remission (CR), one patient had good partial response (GPR) (> 75% reduction in initial bulk) to primary therapy and six were in first complete remission. The patients transplanted in first CR all has a Scotland and Newcastle Lymphoma Group (SNLG) Prognostic Index (Proctor et al., 1991) which indicated they were in a poor risk prognostic group. Melphalan and etoposide both have a short half life enabling ABMT to be accomplished using unmanipulated marrow stored at 4 degrees C. The marrow was returned to the patient within 56 h of harvest. Complete haematological reconstitution occurred in 16/17 patients, the rate of engraftment reflecting the amount of previous chemotherapy. One patient died of progressive Hodgkin's disease before full engraftment could occur. In patients autografted in first remission, the median number of days with neutropenia (< 0.5 x 10(9) l-1 neutrophils) was 19 (range 9-33) and, in those in subsequent remission, 27 days (range 18-36). The median number of days to 50 x 10(9) l-1 platelets in the same groups were 29 (21-80) and 50 (41-74) respectively. The number of days in hospital post transplant in both groups was similar; median 22 (15-27) and 23 (17-37) respectively. There were no procedural deaths and none of the patients transplanted in first, second or third CR have relapsed (median follow up 21 months). The two patients transplanted with progressive disease showed only temporary responses. The two patients transplanted in fourth relapse went into CR; one is still alive and in CR 15 months post transplant, but the other relapsed 18 months post transplant. This form of intensification therapy with marrow rescue has been shown to be effective and of low toxicity and now forms part of a randomised controlled trial in poor risk Hodgkin's patients as identified by the SNLG index (Proctor et al., 1992).


Neuronal c-Abl overexpression leads to neuronal loss and neuroinflammation in the mouse forebrain.
Several immunocytochemical studies have revealed that Abelson tyrosine kinase (c-Abl) is associated with both neuritic plaques and neurofibrillary tangles in the brains of patients with Alzheimer's disease (AD). Additionally, c-Abl has been shown to phosphorylate tau on tyrosine 394. The activity of c-Abl is also involved in the control of the cell cycle and apoptosis. To examine the consequences of c-Abl activation in the adult brain, we have constructed two lines of transgenic mice expressing either a constitutively active form of c-Abl (AblPP/tTA mice) or its sister protein, Arg (ArgPP/tTA mice), with a neuron-specific promoter (CamKIIα) regulated by doxycycline (Tet-Off). Expression of active c-Abl in adult mouse forebrain neurons results in severe neurodegeneration, particularly in the CA1 region of the hippocampus. Neuronal loss was preceded and accompanied by substantial microgliosis and astrocyctosis. Despite careful examination, no c-Abl expression is found in glial cells, indicating that neuronal c-Abl expression is responsible for the gliosis. In contrast, ArgPP/tTA mice have no evidence of neuronal loss or gliosis, even though protein expression and kinase activity levels are similar to those in the AblPP/tTA mice. Given the evidence of c-Abl activation in the human AD brain combined with the pathological phenotype of AblPP/tTA mice, it is likely that aberrant c-Abl activity may play a role in neurodegenerative disease.


The first and second decades of AIDS among injecting drug users.
This paper examines findings and trends from the first decade of research on AIDS among injecting drug users as a basis for projecting into the next decade. One of the most disturbing aspects of AIDS and HIV infection among injecting drug users which emerged in the first decade is the globalization of the problem. Further geographic spread can be expected, particularly in developing countries. Rapid spread of HIV among drug injectors has occurred in many different cities, with a lack of AIDS awareness and mechanisms for efficient mixing of the at-risk population appearing to be important contributing factors. Drug injectors have modified their behavior in response to a wide variety of AIDS prevention programs. No single type of prevention program should be viewed as a panacea, and a comprehensive system of programs will undoubtedly be needed. Changing sexual risk behavior has proven to be considerably more difficult than changing drug injection risk behavior, and is an area in need of much more research.


A Randomized Controlled Trial Comparing the Attention Training Technique and Mindful Self-Compassion for Students With Symptoms of Depression and Anxiety.
The Attention Training Technique (ATT) and Mindful Self-Compassion (MSC) are two promising psychological interventions. ATT is a 12-min auditory exercise designed to strengthen attentional control and promote external focus of attention, while MSC uses guided meditation and exercises designed to promote self-compassion. In this randomized controlled trial (RCT), a three-session intervention trial was conducted in which university students were randomly assigned to either an ATT-group (n = 40) or a MSC-group (n = 41). The students were not assessed with diagnostic interviews but had self-reported symptoms of depression, anxiety, or stress. Participants listened to audiotapes of ATT or MSC before discussing in groups how to apply these principles for their everyday struggles. Participants also listened to audiotapes of ATT and MSC as homework between sessions. Participants in both groups showed significant reductions in symptoms of anxiety and depression accompanied by significant increases in mindfulness, self-compassion, and attention flexibility post-intervention. These results were maintained at 6-month follow-up. Improvement in attention flexibility was the only significant unique predictor of treatment response. The study supports the use of both ATT and MSC for students with symptoms of depression and anxiety. Further, it suggests that symptom improvement is related to changes in attention flexibility across both theoretical frameworks. Future studies should focus on how to strengthen the ability for attention flexibility to optimize treatment for emotional disorder.


Rural-urban variations in age at menarche, adult height, leg-length and abdominal adiposity in black South African women in transitioning South Africa.
The pre-pubertal socioeconomic environment may be an important determinant of age at menarche, adult height, body proportions and adiposity: traits closely linked to adolescent and adult health. This study explored differences in age at menarche, adult height, relative leg-length and waist circumference between rural and urban black South African young adult women, who are at different stages of the nutrition and epidemiologic transitions. We compared 18-23 year-old black South African women, 482 urban-dwelling from Soweto and 509 from the rural Mpumalanga province. Age at menarche, obstetric history and household socio-demographic and economic information were recorded using interview-administered questionnaires. Height, sitting-height, hip and waist circumference were measured using standardised techniques. Urban and rural black South African women differed in their age at menarche (at ages 12.7 and 14.5 years, respectively). In urban women, a one-year increase in age at menarche was associated with a 0.65 cm and 0.16% increase in height and relative leg-length ratio, respectively. In both settings, earlier age at menarche and shorter relative leg-length were independently associated with an increase in waist circumference. In black South African women, the earlier onset of puberty, and consequently an earlier growth cessation process, may lead to central fat mass accumulation in adulthood.


Midbrain single units correlating with pupil response to light.
The consensual response of the pupil in the cat was driven by means of a light flux impinging on the contralateral retina. Spike trains recorded extracellularly from single units in the midbrain show correlation with the concurrently recorded pupil area. The temporal dynamics found confirm two earlier studies of sinigle-unit responses and quantitative nerve stimulation. Both of these indicate that most of the 200-millisecond transport delay resides in the neuromuscular apparatus. Neurons whose activity correlated either with constriction with dilatation phases of Change in the pupil area were observed.


Eating increases oxidative damage in a reptile.
While eating has substantial benefits in terms of both nutrient and energy acquisition, there are physiological costs associated with digesting and metabolizing a meal. Frequently, these costs have been documented in the context of energy expenditure while other physiological costs have been relatively unexplored. Here, we tested whether the seemingly innocuous act of eating affects either systemic pro-oxidant (reactive oxygen metabolite, ROM) levels or antioxidant capacity of corn snakes (Pantherophis guttatus) by collecting plasma during absorptive (peak increase in metabolic rate due to digestion of a meal) and non-absorptive (baseline) states. When individuals were digesting a meal, there was a minimal increase in antioxidant capacity relative to baseline (4%), but a substantial increase in ROMs (nearly 155%), even when controlling for circulating nutrient levels. We report an oxidative cost of eating that is much greater than that due to long distance flight or mounting an immune response in other taxa. This result demonstrates the importance of investigating non-energetic costs associated with meal processing, and it begs future work to identify the mechanism(s) driving this increase in ROM levels. Because energetic costs associated with eating are taxonomically widespread, identifying the taxonomic breadth of eating-induced ROM increases may provide insights into the interplay between oxidative damage and life history theory.


Regulation of neurotransmitter release by synapsin III.
Synapsin III is the most recently identified member of the synapsin family, a group of synaptic vesicle proteins that play essential roles in neurotransmitter release and neurite outgrowth. Here, through the generation and analysis of synapsin III knock-out mice, we demonstrate that synapsin III regulates neurotransmitter release in a manner that is distinct from that of synapsin I or synapsin II. In mice lacking synapsin III, the size of the recycling pool of synaptic vesicles was increased, and synaptic depression was reduced. The number of vesicles that fuse per action potential was similar between synapsin III knock-out and wild-type mice, and there was no change in the quantal content of EPSCs; however, IPSCs were greatly reduced in synapsin III-deficient neurons. The density and distribution of synaptic vesicles in presynaptic terminals did not appear to be different in synapsin III knock-out mice in comparison to wild-type littermates. In addition to the changes in neurotransmitter release, we observed a specific delay in axon outgrowth in cultured hippocampal neurons from synapsin III knock-out mice. Our data indicate that synapsin III plays unique roles both in early axon outgrowth and in the regulation of synaptic vesicle trafficking.


Phylogeography of the Indo-West Pacific maskrays (Dasyatidae, Neotrygon): a complex example of chondrichthyan radiation in the Cenozoic.
Maskrays of the genus Neotrygon (Dasyatidae) have dispersed widely in the Indo-West Pacific being represented largely by an assemblage of narrow-ranging coastal endemics. Phylogenetic reconstruction methods reproduced nearly identical and statistically robust topologies supporting the monophyly of the genus Neotrygon within the family Dasyatidae, the genus Taeniura being consistently basal to Neotrygon, and Dasyatis being polyphyletic to the genera Taeniurops and Pteroplatytrygon. The Neotrygon kuhlii complex, once considered to be an assemblage of color variants of the same biological species, is the most derived and widely dispersed subgroup of the genus. Mitochondrial (COI, 16S) and nuclear (RAG1) phylogenies used in synergy with molecular dating identified paleoclimatic fluctuations responsible for periods of vicariance and dispersal promoting population fragmentation and speciation in Neotrygon. Signatures of population differentiation exist in N. ningalooensis and N. annotata, yet a large-scale geological event, such as the collision between the Australian and Eurasian Plates, coupled with subsequent sea-level falls, appears to have separated a once homogeneous population of the ancestral form of N. kuhlii into southern Indian Ocean and northern Pacific taxa some 4-16 million years ago. Repeated climatic oscillations, and the subsequent establishment of land and shallow sea connections within and between Australia and parts of the Indo-Malay Archipelago, have both promoted speciation and established zones of secondary contact within the Indian and Pacific Ocean basins.


Signal quality and data fusion for false alarm reduction in the intensive care unit.
Due to a lack of integration between different sensors, false alarms (FA) in the intensive care unit (ICU) are frequent and can lead to reduced standard of care. We present a novel framework for FA reduction using a machine learning approach to combine up to 114 signal quality and physiological features extracted from the electrocardiogram, photoplethysmograph, and optionally the arterial blood pressure waveform. A machine learning algorithm was trained and evaluated on a database of 4107 expert-labeled life-threatening arrhythmias, from 182 separate ICU visits. On the independent test data, FA suppression results with no true alarm (TA) suppression were 86.4% for asystole, 100% for extreme bradycardia and 27.8% for extreme tachycardia. For the ventricular tachycardia alarms, the best FA suppression performance was 30.5% with a TA suppression rate below 1%. To reduce the TA suppression rate to zero, a reduction in FA suppression performance to 19.7% was required.


Cdc7-Dbf4 phosphorylates MCM proteins via a docking site-mediated mechanism to promote S phase progression.
Origins of DNA replication are licensed in G1 by recruiting the minichromosome maintenance (MCM) proteins to form a prereplicative complex (pre-RC). Prior to initiation of DNA synthesis from each origin, a preinitiation complex (pre-IC) containing Cdc45 and other proteins is formed. We report that Cdc7-Dbf4 protein kinase (DDK) promotes assembly of a stable Cdc45-MCM complex exclusively on chromatin in S phase. In this complex, Mcm4 is hyperphosphorylated. Studies in vitro using purified DDK and Mcm4 demonstrate that hyperphosphorylation occurs at the Mcm4 N terminus. However, the DDK substrate specificity is conferred by an adjacent DDK-docking domain (DDD), sufficient for facilitating efficient phosphorylation of artificial phosphoacceptors in cis. Genetic evidence suggests that phosphorylation of Mcm4 by DDK is important for timely S phase progression and for cell viability upon overproduction of Cdc45. We suggest that DDK docks on and phosphorylates MCM proteins at licensed origins to promote proper assembly of pre-IC.


Analysis of human MDM4 variants in papillary thyroid carcinomas reveals new potential markers of cancer properties.
A wild-type (wt) p53 gene characterizes thyroid tumors, except for the rare anaplastic histotype. Because p53 inactivation is a prerequisite for tumor development, alterations of p53 regulators represent an alternative way to impair p53 function. Indeed, murine double minute 2 (MDM2), the main p53 negative regulator, is overexpressed in many tumor histotypes including those of the thyroid. A new p53 regulator, MDM4 (a.k.a. MDMX or HDMX) an analog of MDM2, represents a new oncogene although its impact on tumor properties remains largely unexplored. We estimated levels of MDM2, MDM4, and its variants, MDM4-S (originally HDMX-S) and MDM4-211 (originally HDMX211), in a group of 57 papillary thyroid carcinomas (PTC), characterized by wt tumor protein 53, in comparison to matched contra-lateral lobe normal tissue. Further, we evaluated the association between expression levels of these genes and the histopathological features of tumors. Quantitative real-time polymerase chain reaction revealed a highly significant downregulation of MDM4 mRNA in tumor tissue compared to control tissue (P<0.0001), a finding confirmed by western blot on a subset of 20 tissue pairs. Moreover, the tumor-to-normal ratio of MDM4 levels for each individual was significantly lower in late tumor stages, suggesting a specific downregulation of MDM4 expression with tumor progression. In comparison, MDM2 messenger RNA (mRNA) and protein levels were frequently upregulated with no correlation with MDM4 levels. Lastly, we frequently detected overexpression of MDM4-S mRNA and presence of the aberrant form, MDM4-211 in this tumor group. These findings indicate that MDM4 alterations are a frequent event in PTC. It is worthy to note that the significant downregulation of full-length MDM4 in PTC reveals a novel status of this factor in human cancer that counsels careful evaluation of its role in human tumorigenesis and of its potential as therapeutic target.


Systematic review of reviews of behavioural HIV prevention interventions among men who have sex with men.
Men who have sex with men (MSM) remain one of the groups most at risk of HIV. The growing evidence-base on behavioural HIV prevention interventions includes systematic review-level evidence, including reviews specific to MSM populations. Here, we provide an up-to-date review of these systematic reviews in which we examined the effectiveness of behavioural HIV prevention interventions among MSM. A systematic search of electronic databases, including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, PsycInfo, from January 2000 to October 2010, along with hand searches of the reference lists of retrieved documents were conducted. Inclusion criteria included: study design limited to systematic reviews and meta-analyses; methodological quality; and review to focus on MSM and behavioural interventions. A narrative synthesis was conducted. Across the four included meta-analyses (102 studies; 52 independent studies), there was strong and consistent evidence for group- and community-level interventions being associated with reductions in UAI (27-30% and 30%, respectively) and increases in condom use amongst MSM, but inconsistent evidence for the effectiveness of individual-level interventions. Skills-building, trained professionals delivering the training and theory-based interventions were also consistently effective. The inherent limitations of the review of review method within a changing health domain meant it was difficult to develop contemporary and directly transferable guidance to HIV prevention policy development. However, the analysis does demonstrate a need for a step change in the kinds of data that are collated in the development of future systematic reviews of HIV prevention interventions among MSM.


Triage in the Tower of Babel: interpreter services for children in the prehospital setting.
Minority pediatric populations have higher rates of emergency medical services use than the general pediatric population, and prior studies have documented that limited-English proficiency patients are more likely to undergo invasive procedures, require more resources, and be admitted once they arrive in the emergency department. Furthermore, limited-English proficiency patients may be particularly vulnerable because of immigration or political concerns. In this case report, we describe an infant with breath-holding spells for whom a language barrier in the prehospital setting resulted in an escalation of care to the highest level of trauma team activation. This infant underwent unnecessary, costly, and harmful interventions because of a lack of interpreter services. In a discussion of the legal, ethical, and medical implications of this case, we conclude that further investigation into prehospital strategies for overcoming language barriers is required to provide optimal prehospital care for pediatric patients.


Hydrogeochemical controls on brook trout spawning habitats in a coastal stream.
Brook trout (Salvelinus fontinalis) spawn in fall and overwintering egg development can benefit from stable, relatively warm temperatures in groundwater-seepage zones. However, eggs are also sensitive to dissolved oxygen concentration, which may be reduced in discharging groundwater (i.e., seepage). We investigated a 2 km reach of the coastal Quashnet River in Cape Cod, Massachusetts, USA, to relate preferred fish spawning habitats to geology, geomorphology, and discharging groundwater geochemistry. Thermal reconnaissance methods were used to locate zones of rapid groundwater discharge, which were predominantly found along the central channel of a wider stream valley section. Pore-water chemistry and temporal vertical groundwater flux were measured at a subset of these zones during field campaigns over several seasons. Seepage zones in open-valley sub-reaches generally showed suboxic conditions and higher dissolved solutes compared to the underlying glacial outwash aquifer. These discharge zones were cross-referenced with preferred brook trout redds and evaluated during 10 years of observation, all of which were associated with discrete alcove features in steep cutbanks, where stream meander bends intersect the glacial valley walls. Seepage in these repeat spawning zones was generally stronger and more variable than in open-valley sites, with higher dissolved oxygen and reduced solute concentrations. The combined evidence indicates that regional groundwater discharge along the broader valley bottom is predominantly suboxic due to the influence of near-stream organic deposits; trout show no obvious preference for these zones when spawning. However, the meander bends that cut into sandy deposits near the valley walls generate strong oxic seepage zones that are utilized routinely for redd construction and the overwintering of trout eggs. Stable water isotopic data support the conclusion that repeat spawning zones are located directly on preferential discharges of more localized groundwater. In similar coastal systems with extensive valley peat deposits, the specific use of groundwater-discharge points by brook trout may be limited to morphologies such as cutbanks, where groundwater flow paths do not encounter substantial buried organic material and remain oxygen-rich.


Recommendations on chronic constipation (including constipation associated with irritable bowel syndrome) treatment.
While chronic constipation (CC) has a high prevalence in primary care, there are no existing treatment recommendations to guide health care professionals. To address this, a consensus group of 10 gastroenterologists was formed to develop treatment recommendations. Although constipation may occur as a result of organic disease, the present paper addresses only the management of primary CC or constipation associated with irritable bowel syndrome. The final consensus group was assembled and the recommendations were created following the exact process outlined by the Canadian Association of Gastroenterology for the following areas: epidemiology, quality of life and threshold for treatment; definitions and diagnostic criteria; lifestyle changes; bulking agents and stool softeners; osmotic agents; prokinetics; stimulant laxatives; suppositories; enemas; other drugs; biofeedback and behavioural approaches; surgery; and probiotics. A treatment algorithm was developed by the group for CC and constipation associated with irritable bowel syndrome. Where possible, an evidence-based approach and expert opinions were used to develop the statements in areas with insufficient evidence. The nature of the underlying pathophysiology for constipation is often unclear, and it can be tricky for physicians to decide on an appropriate treatment strategy for the individual patient. The myriad of treatment options available to Canadian physicians can be confusing; thus, the main aim of the recommendations and treatment algorithm is to optimize the approach in clinical care based on available evidence.


Inhibitor binding induces active site stabilization of the HCV NS3 protein serine protease domain.
Few structures of viral serine proteases, those encoded by the Sindbis and Semliki Forest viruses, hepatitis C virus (HCV) and cytomegalovirus, have been reported. In the life cycle of HCV a crucial role is played by a chymotrypsin-like serine protease encoded at the N-terminus of the viral NS3 protein, the solution structure of which we present here complexed with a covalently bound reversible inhibitor. Unexpectedly, the residue in the P2 position of the inhibitor induces an effective stabilization of the catalytic His-Asp hydrogen bond, by shielding that region of the protease from the solvent. This interaction appears crucial in the activation of the enzyme catalytic machinery and represents an unprecedented observation for this family of enzymes. Our data suggest that natural substrates of this serine protease could contribute to the enzyme activation by a similar induced-fit mechanism. The high degree of similarity at the His-Asp catalytic site region between HCV NS3 and other viral serine proteases suggests that this behaviour could be a more general feature for this category of viral enzymes.


Cardiac vagal tone, a non-invasive measure of parasympathetic tone, is a clinically relevant tool in Type 1 diabetes mellitus.
To compare a novel index of parasympathetic tone, cardiac vagal tone, with established autonomic variables and to test the hypotheses that (1) cardiac vagal tone would be associated with established time and frequency domain measures of heart rate and (2) cardiac vagal tone would be lower in people with Type 1 diabetes than in a matched healthy cohort and lower still in people with established neuropathy. Cardiac vagal tone is a validated cardiometrically derived index of parasympathetic tone. It is measured using a standard three-lead electrocardiogram which connects, via Bluetooth, to a smartphone application. A 5-min resting recording of cardiac vagal tone was undertaken and observational comparisons were made between 42 people with Type 1 diabetes and peripheral neuropathy and 23 without peripheral neuropathy and 65 healthy people. In those with neuropathy, 24-h heart rate variability values were compared with cardiac vagal tone. Correlations between cardiac vagal tone and clinical variables were also made. Cardiac vagal tone was lower in people with established neuropathy and Type 1 diabetes in comparison with healthy participants [median (interquartile range) linear vagal scale 3.4 (1.6-5.5 vs 7.0 (5.5-9.6); P < 0.0001]. Cardiac vagal tone was positively associated with time (r = 0.8, P < 0.0001) and frequency domain markers of heart rate variability (r = 0.75, P < 0.0001), representing established measures of parasympathetic function. Cardiac vagal tone was negatively associated with age (r=-0.32, P = 0.003), disease duration (r=-0.43, P < 0.0001) and cardiovascular risk score (r=-0.32, P = 0.006). Cardiac vagal tone represents a convenient, clinically relevant method of assessing parasympathetic nervous system tone, potentially facilitating the earlier identification of people with Type 1 diabetes who should undergo formal autonomic function testing.


Developing the practice context to enable more effective pain management with older people: an action research approach.
This paper, which draws upon an Emancipatory Action Research (EAR) approach, unearths how the complexities of context influence the realities of nursing practice. While the intention of the project was to identify and change factors in the practice context that inhibit effective person-centred pain management practices with older people (65 years or older), reflective critical engagement with the findings identified that enhancing pain management practices with older people was dependent on cultural change in the unit as a whole. An EAR approach was utilised. The project was undertaken in a surgical unit that conducted complex abdominal surgery. Eighty-five percent (n = 48) of nursing staff participated in the two-year project (05/NIR02/107). Data were obtained through the use of facilitated critical reflection with nursing staff. Three key themes (psychological safety, leadership, oppression) and four subthemes (power, horizontal violence, distorted perceptions, autonomy) were found to influence the way in which effective nursing practice was realised. Within the theme of 'context,' effective leadership and the creation of a psychologically safe environment were key elements in the enhancement of all aspects of nursing practice. Whilst other research has identified the importance of 'practice context' and models and frameworks are emerging to address this issue, the theme of 'psychological safety' has been given little attention in the knowledge translation/implementation literature. Within the principles of EAR, facilitated reflective sessions were found to create 'psychologically safe spaces' that supported practitioners to develop effective person-centred nursing practices in complex clinical environments.


Inhibitory effect of gut bacteria from the Japanese honey bee, Apis cerana japonica, against Melissococcus plutonius, the causal agent of European foulbrood disease.
European foulbrood is a contagious bacterial disease of honey bee larvae. Studies have shown that the intestinal bacteria of insects, including honey bees, act as probiotic organisms. Microbial flora from the gut of the Japanese honey bee, Apis cerana japonica F. (Hymenoptera: Apidae), were characterized and evaluated for their potential to inhibit the growth of Melissococcus plutonius corrig. (ex White) Bailey and Collins (Lactobacillales: Enterococcaceae), the causative agent of European foulbrood. Analysis of 16S rRNA gene sequences from 17 bacterial strains isolated by using a culture-dependent method revealed that most isolates belonged to Bacillus, Staphylococcus, and Pantoea. The isolates were screened against the pathogenic bacterium M. plutonius by using an in vitro growth inhibition assay, and one isolate (Acja3) belonging to the genus Bacillus exhibited inhibitory activity against M. plutonius. In addition, in vivo feeding assays revealed that isolate Acja3 decreased the mortality of honey bee larvae infected with M plutonius, suggesting that this bacterial strain could potentially be used as a probiotic agent against European foulbrood.


High prevalence of hearing impairment in HIV-infected Peruvian children.
To measure the prevalence and to identify risk factors of hearing impairment in human immunodeficiency virus-infected children living in Peru. Cross-sectional observational study. Two public hospitals and 1 nonprofit center in Lima, Peru, between August 2009 and April 2010. A total of 139 HIV-infected children, ages 4 to 19 years. Hearing impairment and otologic health were assessed with pure tone audiometry, tympanometry, and otoscopy. The primary outcome was hearing loss, defined as average threshold >25dB for 0.5, 1, 2, and 4 kHz, in one or both ears. Historical and socioeconomic information was obtained through parental survey and medical chart review. Statistical analysis included univariate analysis and multivariate logistic regression. Fifty-four (38.8%) of 139 children had hearing impairment. On multivariate analysis, risk factors included: tympanic membrane perforation (odds ratio [OR] 7.08; 95% confidence interval [CI], 1.65-30.5; P = .01), abnormal tympanometry (OR 2.71; 95% CI, 1.09-6.75; P = .03), cerebral infection (OR 11.6; 95% CI, 1.06-126; P = .05), seizures (OR 5.20; 95% CI, 1.21-22.4; P = .03), and CD4 cell count <500 cells/mm(3) (OR 3.53; 95% CI, 1.18-10.5; P = .02). The prevalence of hearing impairment in HIV-infected children in Lima, Peru was 38.8%. Middle ear disease, prior cerebral infection, and low CD4 cell count were significantly associated with hearing impairment. The high prevalence of hearing impairment emphasizes the need for periodic hearing assessment in the routine clinical care of HIV-infected children.


Limits to sustained energy intake. XXII. Reproductive performance of two selected mouse lines with different thermal conductance.
Maximal sustained energy intake (SusEI) appears limited, but the factors imposing the limit are disputed. We studied reproductive performance in two lines of mice selected for high and low food intake (MH and ML, respectively), and known to have large differences in thermal conductance (29% higher in the MH line at 21°C). When these mice raised their natural litters, their metabolisable energy intake significantly increased over the first 13 days of lactation and then reached a plateau. At peak lactation, MH mice assimilated on average 45.3% more energy than ML mice (222.9±7.1 and 153.4±12.5 kJ day(-1), N=49 and 24, respectively). Moreover, MH mice exported on average 62.3 kJ day(-1) more energy as milk than ML mice (118.9±5.3 and 56.6±5.4 kJ day(-1), N=subset of 32 and 21, respectively). The elevated milk production of MH mice enabled them to wean litters (65.2±2.1 g) that were on average 50.2% heavier than litters produced by ML mothers (43.4±3.0 g), and pups that were on average 27.2% heavier (9.9±0.2 and 7.8±0.2 g, respectively). Lactating mice in both lines had significantly longer and heavier guts compared with non-reproductive mice. However, inconsistent with the 'central limit hypothesis', the ML mice had significantly longer and heavier intestines than MH mice. An experiment where the mice raised litters of the opposing line demonstrated that lactation performance was not limited by the growth capacity of offspring. Our findings are consistent with the idea that the SusEI at peak lactation is constrained by the capacity of the mothers to dissipate body heat.


The spontaneous expression of pride and shame: evidence for biologically innate nonverbal displays.
The present research examined whether the recognizable nonverbal expressions associated with pride and shame may be biologically innate behavioral responses to success and failure. Specifically, we tested whether sighted, blind, and congenitally blind individuals across cultures spontaneously display pride and shame behaviors in response to the same success and failure situations--victory and defeat at the Olympic or Paralympic Games. Results showed that sighted, blind, and congenitally blind individuals from >30 nations displayed the behaviors associated with the prototypical pride expression in response to success. Sighted, blind, and congenitally blind individuals from most cultures also displayed behaviors associated with shame in response to failure. However, culture moderated the shame response among sighted athletes: it was less pronounced among individuals from highly individualistic, self-expression-valuing cultures, primarily in North America and West Eurasia. Given that congenitally blind individuals across cultures showed the shame response to failure, findings overall are consistent with the suggestion that the behavioral expressions associated with both shame and pride are likely to be innate, but the shame display may be intentionally inhibited by some sighted individuals in accordance with cultural norms.


The neural correlates of highly iconic structures and topographic discourse in French Sign Language as observed in six hearing native signers.
"Highly iconic" structures in Sign Language enable a narrator to act, switch characters, describe objects, or report actions in four-dimensions. This group of linguistic structures has no real spoken-language equivalent. Topographical descriptions are also achieved in a sign-language specific manner via the use of signing-space and spatial-classifier signs. We used functional magnetic resonance imaging (fMRI) to compare the neural correlates of topographic discourse and highly iconic structures in French Sign Language (LSF) in six hearing native signers, children of deaf adults (CODAs), and six LSF-naïve monolinguals. LSF materials consisted of videos of a lecture excerpt signed without spatially organized discourse or highly iconic structures (Lect LSF), a tale signed using highly iconic structures (Tale LSF), and a topographical description using a diagrammatic format and spatial-classifier signs (Topo LSF). We also presented texts in spoken French (Lect French, Tale French, Topo French) to all participants. With both languages, the Topo texts activated several different regions that are involved in mental navigation and spatial working memory. No specific correlate of LSF spatial discourse was evidenced. The same regions were more activated during Tale LSF than Lect LSF in CODAs, but not in monolinguals, in line with the presence of signing-space structure in both conditions. Motion processing areas and parts of the fusiform gyrus and precuneus were more active during Tale LSF in CODAs; no such effect was observed with French or in LSF-naïve monolinguals. These effects may be associated with perspective-taking and acting during personal transfers.


Ascomycetes from the Qilian Mountains, China - Hypocreales.
To investigate fungi from the Qilian Mountains in Gansu Province, ascomycetous specimens were collected and hypocrealean fungi were examined. Eighteen species belonging to six genera in the families Hypocreaceae and Nectriaceae were identified, including 11 species of Hypomyces and Trichoderma in Hypocreaceae and seven species of Nectria, Stylonectria, Thelonectria, and Thyronectria in Nectriaceae. Among them, Stylonectria qilianshanensis and Trichoderma gansuanum are new to science. DNA sequence analyses of combined ACL1, ITS, RPB2, and TEF1 regions confirmed their taxonomic placements. Morphological distinctions between the new species and their close relatives are discussed. Hypomyces tremellicola is reported for the first time in China.


Sharing clinical research data in the United States under the Health Insurance Portability and Accountability Act and the Privacy Rule.
Sharing of final research data from clinical research is an essential part of the scientific method. The U.S. National Institutes of Health require some grant applications to include plans for sharing final research data, which it defines as the factual materials necessary to document, support, and validate research findings. In the U.S., however, the Privacy Rule adopted under the Health Insurance Portability and Accountability Act impedes the sharing of final research data. In most situations, final research data may be shared only where all information that could possibly be used to identify the subject has been deleted, or where the subject has given authorization for specific research, or an Institutional Review Board has granted a waiver.


Taking lanthanides out of isolation: tuning the optical properties of metal-organic frameworks.
Metal organic frameworks (MOFs) are increasingly used in applications that rely on the optical and electronic properties of these materials. These applications require a fundamental understanding on how the structure of these materials, and in particular the electronic interactions of the metal node and organic linker, determines these properties. Herein, we report a combined experimental and computational study on two families of lanthanide-based MOFs: Ln-SION-1 and Ln-SION-2. Both comprise the same metal and ligand but with differing structural topologies. In the Ln-SION-2 series the optical absorption is dominated by the ligand and using different lanthanides has no impact on the absorption spectrum. The Ln-SION-1 series shows a completely different behavior in which the ligand and the metal node do interact electronically. By changing the lanthanide in Ln-SION-1, we were able to tune the optical absorption from the UV region to absorption that includes a large part of the visible region. For the early lanthanides we observe intraligand (electronic) transitions in the UV region, while for the late lanthanides a new band appears in the visible. DFT calculations showed that the new band in the visible originates in the spatial orbital overlap between the ligand and metal node. Our quantum calculations indicated that Ln-SION-1 with late lanthanides might be (photo)conductive. Experimentally, we confirm that these materials are weakly conductive and that with an appropriate co-catalysts they can generate hydrogen from a water solution using visible light. Our experimental and theoretical analysis provides fundamental insights for the rational design of Ln-MOFs with the desired optical and electronic properties.


Comparison of four different crystal forms of the Mycobacterium tuberculosis ESX-1 secreted protein regulator EspR.
The Mycobacterium tuberculosis ESX-1 secreted protein regulator (EspR, Rv3849) is the key protein that delivers bacterial proteins into the host cell during mycobacterial infection. EspR binds directly to the espACD operon and is involved in transcriptional activation. In the current study, M. tuberculosis EspR has been crystallized and its X-ray structure has been determined at 3.3 Å resolution in a P3221 crystal form. EspR forms a physiological dimer in the crystal. Each EspR monomer contains an N-terminal helix-turn-helix DNA-binding domain and a C-terminal dimerization domain. The EspR structure in the P3221 crystal form was compared with previously determined EspR structures in P32, P21 and P212121 crystal forms. Structural comparison analysis indicated that the N-terminal helix-turn-helix domain of EspR acquires a rigid structure in the four crystal forms. However, significant structural differences were observed in the C-terminal domain of EspR in the P21 crystal form when compared with the P3221 and P32 crystal forms. The interaction, stabilization energy and buried surface area analysis of EspR in the four different crystal forms have provided information about the physiological dimer interface of EspR.


GI manifestations of Ehlers-Danlos syndrome.
Ehlers-Danlos syndrome (EDS) is an inherited disorder of connective tissue that is distinguished not only by the triad of skin hyperextensibility, articular hypermobility, and tissue fragility but also by its heterogeneity on clinical, genetic, and biochemical grounds. The phenotypical variance that characterizes this syndrome often makes its recognition difficult, and failure to recognize the disease despite a classic course is not uncommon. Diagnosis is paramount, however, so life-threatening associations can be searched for and unique principles of management can be instituted. Patients are prone to GI catastrophes such as perforation and massive bleeding, which can be compounded by grave surgical and vascular complications. A thorough knowledge of the GI manifestations of EDS and their management is mandatory to prevent unnecessary morbidity and mortality.


Caffeic acid, tyrosol and p-coumaric acid are potent inhibitors of 5-S-cysteinyl-dopamine induced neurotoxicity.
Parkinson's disease is characterized by a progressive and selective loss of dopaminergic neurons in the substantia nigra. Recent investigations have shown that conjugates such as the 5-S-cysteinyl-dopamine, possess strong neurotoxicity and may contribute to the underlying progression of the disease pathology. Although the neuroprotective actions of flavonoids are well reported, that of hydroxycinnamates and other phenolic acids is less established. We show that the hydroxycinnamates caffeic acid and p-coumaric acid, the hydroxyphenethyl alcohol, tyrosol, and a Champagne wine extract rich in these components protect neurons against injury induced by 5-S-cysteinyl-dopamine in vitro. The protection induced by these polyphenols was equal to or greater than that observed for the flavonoids, (+)-catechin, (-)-epicatechin and quercetin. For example, p-coumaric acid evoked significantly more protection at 1muM (64.0+/-3.1%) than both (-)-epicatechin (46.0+/-4.1%, p<0.05) and (+)-catechin (13.1+/-3.0%, p<0.001) at the same concentration. These data indicate that hydroxycinnamates, phenolic acids and phenolic alcohol are also capable of inducing neuroprotective effects to a similar extent to that seen with flavonoids.


[Assessment of so called organic trace compounds in drinking water from the regulatory, health and aesthetic-quality points of view, with special consideration given to pharmaceuticals].
More than 2500 chemically defined substances are approved as drugs in Germany. Unlike agricultural pesticides, these biologically active structures are not used in open environmental compartments and therefore their environmental toxicological data base is not nearly as complete. Nevertheless, some of them become environmental contaminants after their intended use. Therefore, from the viewpoint of environmental health protection, there are gaps in their health-related environmental risk assessment. Organic trace compounds that lack an adequate toxicological database, and their mixtures, in drinking water can be safely regulated and provisionally assessed by combining the "similar joint action" addition rule with the recommendation of the Federal Environment Agency of March 2003 "Assessing the presence of substances in drinking water without (adequate) toxicological database from the health point of view". The general precautionary value (Gesundheitlicher Orientierungswert GOW1=0.10 microg/l), which is a recommendation for weakly to not genotoxic compounds, re presents a workable compromise between preventive health protection, water management considerations and aesthetic quality claims (purity). Compliance with this value in the long term will only be possible if the chemical and biological degradation of pharmaceuticals and their metabolites in waste water and waste water treatment plants is effectively improved. Alternatively, there is the risk of drinking water degenerating into a sink for highly mobile, polar and persistent compounds. Their elimination at a stage as late as technical drinking water treatment would be neither close to the initial cause nor justifiable in terms of technical effectiveness. The risk assessment of their byproducts would give rise to further uncertainties. Possible conflicts with the therapeutic quality must be solved by developing substitute products which are environmentally sound.


The promise of electrochemical impedance spectroscopy as novel technology for the management of patients with diabetes mellitus.
Self-monitoring of blood glucose is the standard of care in management of hyperglycemia among patients with diabetes mellitus. To increase the sensitivity and specificity of current devices, a novel method of detecting glucose using electrochemical impedance spectroscopy (EIS) technology is explored. The enzyme glucose oxidase (GOx) was fixed to gold electrodes and a sine wave of sweeping frequencies was induced using a wide range of concentrations of glucose. Each frequency in the impedance sweep was analyzed for the highest response and R-squared value. The frequency with both factors optimized is specific for the glucose-GOx binding interaction and was determined to be 1.17 kHz in purified solutions in both higher and lower ranges of glucose. The correlation between the impedance response and concentration at the low range of detection (0-100 mg dL(-1) of glucose) was determined to be 3.53 ohm/ln (mg dL(-1)) with an R-squared value of 0.90 with a 39 mg dL(-1) lower limit of detection. The same frequency of 1.17 kHz was verified in whole blood under the same glucose range. The above data confirm that EIS offers a new method of glucose detection as an alternative to current technology in use by patients. Additionally, the unique frequency response of individual markers allows for modulation of signals so that several other markers important in the management of diabetes could be measured with a single sensor.


Findings in Stillbirths Associated with Placental Disease.
Placental disease is a leading cause of stillbirth. Our purpose was to characterize stillbirths associated with placental disease. The Stillbirth Collaborative Research Network conducted a prospective, case-control study of stillbirths and live births from 2006 to 2008. This analysis includes 512 stillbirths with cause of death assignment and a comparison group of live births. We compared exposures between women with stillbirth due to placental disease and those due to other causes as well as between women with term (≥ 37 weeks) stillbirth due to placental disease and term live births. A total of 121 (23.6%) out of 512 stillbirths had a probable or possible cause of death due to placental disease by Initial Causes of Fetal Death. Characteristics were similar between stillbirths due to placental disease and other stillbirths. When comparing term live births to stillbirths due to placental disease, women with non-Hispanic black race, Hispanic ethnicity, lack of insurance, or who were born outside of the United States had higher odds of stillbirth due to placental disease. Nulliparity and antenatal bleeding also increased risk of stillbirth due to placental disease. Multiple discrete exposures were associated with stillbirth caused by placental disease. The relationship between these factors and utility of surveillance warrants further study.


Preference of a native beetle for "exoticism," characteristics that contribute to invasive success of Costelytra zealandica (Scarabaeidae: Melolonthinae).
Widespread replacement of native ecosystems by productive land sometimes results in the outbreak of a native species. In New Zealand, the introduction of exotic pastoral plants has resulted in diet alteration of the native coleopteran species, Costelytra zealandica (White) (Scarabaeidae) such that this insect has reached the status of pest. In contrast, C. brunneum (Broun), a congeneric species, has not developed such a relationship with these 'novel' host plants. This study investigated the feeding preferences and fitness performance of these two closely related scarab beetles to increase fundamental knowledge about the mechanisms responsible for the development of invasive characteristics in native insects. To this end, the feeding preference of third instar larvae of both Costelytra species was investigated using an olfactometer device, and the survival and larval growth of the invasive species C. zealandica were compared on native and exotic host plants. Costelytra zealandica, when sampled from exotic pastures, was unable to fully utilise its ancestral native host and showed higher feeding preference and performance on exotic plants. In contrast, C. zealandica sampled from native grasslands did not perform significantly better on either host and showed similar feeding preferences to C. brunneum, which exhibited no feeding preference. This study suggests the possibility of strong intraspecific variation in the ability of C. zealandica to exploit native or exotic plants, supporting the hypothesis that such ability underpins the existence of distinct host-races in this species.


Spatiotemporal magnetic field monitoring for MR.
MR experiments frequently rely on signal encoding by the application of magnetic fields that vary in both space and time. The accurate interpretation of the resulting signals often requires knowledge of the exact spatiotemporal field evolution during the experiment. To better fulfill this need, a new approach is presented that enables measuring the field evolution concurrently with any MR sequence. Miniature NMR probes are used to monitor the MR phase evolution around the object under investigation. Based on these data, a global phase model is calculated that can then be used as a basis for processing the actual image or spectroscopic data. The new method is demonstrated by MRI of a phantom, using spin-warp, spiral, and EPI trajectories. Throughout, the monitoring results enabled highly accurate image reconstruction, even in the presence of massive gradient imperfections.


Experimental demonstration of quantum digital signatures using phase-encoded coherent states of light.
Digital signatures are frequently used in data transfer to prevent impersonation, repudiation and message tampering. Currently used classical digital signature schemes rely on public key encryption techniques, where the complexity of so-called 'one-way' mathematical functions is used to provide security over sufficiently long timescales. No mathematical proofs are known for the long-term security of such techniques. Quantum digital signatures offer a means of sending a message, which cannot be forged or repudiated, with security verified by information-theoretical limits and quantum mechanics. Here we demonstrate an experimental system, which distributes quantum signatures from one sender to two receivers and enables message sending ensured against forging and repudiation. Additionally, we analyse the security of the system in some typical scenarios. Our system is based on the interference of phase-encoded coherent states of light and our implementation utilizes polarization-maintaining optical fibre and photons with a wavelength of 850 nm.


CO2 emissions boost the benefits of crop production by farming damselfish.
Farming is a technique employed by both humans and animals to enhance crop yields, allowing their populations to increase beyond the natural carrying capacity of the environment. Using volcanic CO2 vents, we investigate how a species of herbivorous fish (the black scalyfin Parma alboscapularis) may use increasing anthropogenic CO2 emissions to enhance its crop yields. We found that these farming fish can take advantage of this resource enrichment, to grow crops within smaller territories and increase the capacity of the environment to support more densely packed fish populations.


Improving hand hygiene behaviour of nurses using action planning: a pilot study in the intensive care unit and surgical ward.
Compliance with hand hygiene guidelines by hospital physicians and nurses is universally low and there is a need to apply powerful intervention methods from social sciences in order to improve compliance. One method is the formation of implementation intentions (or action planning) in which concrete 'if then' plans are formulated to link an environmental cue with performance of an intended behavioural action. This pilot study explored the practicality and effects of action planning on the hand hygiene behaviour (HHB) of nurses in an ICU and surgical ward of a university teaching hospital. A pre-post test design was used, and 17 nurses were invited to participate. A trained researcher observed HHB of nurses before and three weeks after the intervention in which action plans were formulated. Frequencies were calculated and logistic regression analysis was performed to assess changes in HHB. Of the 17 participants, 10 (seven in surgical ward, three in ICU) had complete data and were included in the analyses. In total, 283 potential moments for hand hygiene were identified, 142 in the surgical ward and 141 in the ICU. HHB increased from 9.3% at baseline to 25.4% post intervention (odds ratio: 3.3; confidence interval: 1.7-6.5; P<0.001). Although this was a small scale study, the results show promise for the use of action planning to improve the HHB of nurses in the short term. Action planning has shown success in closing the intention-behaviour gap in other fields, and its use for improving HHB in healthcare should be further investigated.