Enhanced imaging algorithm for scanning laser polarimetry with variable corneal compensation.
To describe and investigate a method of improving assessment of retinal nerve fiber layer (RNFL) morphology with scanning laser polarimetry (SLP) with variable corneal compensation (VCC). By neutralizing anterior segment birefringence with a variable compensator, the current VCC method allows direct measurement of RNFL retardation. In the new method, enhanced corneal compensation (ECC), the variable compensator was set to introduce a "bias" birefringence. This bias was removed mathematically for each individual pixel to produce the RNFL image. In 177 eyes of healthy subjects, patients with glaucoma, and subjects with ocular hypertension, retardation images were obtained with both VCC and ECC. In the tested eyes, images obtained with ECC showed the expected RNFL appearance better than those obtained with VCC. In addition, the typical scan score, which quantifies the amount of atypia, was higher with ECC than with VCC. The amount of residual anterior segment birefringence dropped significantly with ECC in the various groups. Measurements of peripapillary RNFL retardation showed reduced temporal and nasal values with ECC, whereas superior and inferior values were not significantly different between VCC and ECC. The dynamic range appeared to have increased with ECC. The accuracy of the TSNIT (temporal, superior, nasal, inferior, temporal) average and inferior average for detecting glaucoma was higher with ECC than with VCC. RNFL morphology may be better assessed with the presented ECC method than with standard VCC. ECC may be implemented in the current VCC systems by means of a software upgrade. It may enhance the clinical utility of the GDx VCC in glaucoma management.


Effects of Body Mass Index and Body Fat Percent on Default Mode, Executive Control, and Salience Network Structure and Function.
It is well established that obesity decreases overall life expectancy and increases the risk of several adverse health conditions. Mounting evidence indicates that body fat is likely also associated with structural and functional brain changes, reduced cognitive function, and greater impulsivity. However, previously reported differences in brain structure and function have been variable across studies and difficult to reconcile due to sample population and methodological differences. To clarify these issues, we correlated two independent measures of body composition-i.e., body mass index (BMI) and body fat percent (BFP)-with structural and functional neuroimaging data obtained from a cohort of 32 neurologically healthy adults. Whole-brain voxel-wise analyses indicated that higher BMI and BFP were associated with widespread decreases in gray matter volume, white matter volume, and white matter microstructure (including several regions, such as the striatum and orbitofrontal cortex, which may influence value assessment, habit formation, and decision-making). Moreover, closer examination of resting state functional connectivity, white matter volume, and white matter microstructure throughout the default mode network (DMN), executive control network (ECN), and salience network (SN) revealed that higher BMI and BFP were associated with increased SN functional connectivity and decreased white matter volumes throughout all three networks (i.e., the DMN, ECN, and SN). Taken together, these findings: (1) offer a biologically plausible explanation for reduced cognitive performance, greater impulsivity, and altered reward processing among overweight individuals, and (2) suggest neurobiological mechanisms (i.e., altered functional and structural brain connectivity) that may affect overweight individuals' ability to establish and maintain healthy lifestyle choices.


Tear proteomic analysis of patients with type 2 diabetes and dry eye syndrome by two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry.
Diabetes mellitus has been shown to be associated with and complicated by dry eye syndrome. We sought to examine and compare the tear film proteome of type 2 diabetic patients with or without dry eye syndrome and normal subjects using two-dimensional nano-liquid chromatography coupled with tandem mass spectrometry (MS)-based proteomics. Tears were collected from eight type 2 diabetes patients with dry eye syndrome, eight type 2 diabetes patients without dry eye syndrome, and eight normal subjects. Tear breakup time (BUT) was determined, and tear proteins were prepared and analyzed using two-dimensional strong cation-exchange/reversed-phase nano-scale liquid chromatography MS. All MS/MS spectra were identified by using SEQUEST against the human International Protein Index (IPI) database and the relative abundance of individual proteins was assessed by spectral counting. Tear BUT was significantly lower in patients with diabetes and dry eye syndrome than in patients with diabetes only and normal subjects. Analysis of spectral counts of tear proteins showed that, compared to healthy controls, patients with diabetes and dry eye syndrome had increased expression of apoptosis-related proteins, like annexin A1, and immunity- and inflammation-related proteins, including neutrophil elastase 2 and clusterin, and glycometabolism-related proteins, like apolipoprotein A-II. Dry eye syndrome in diabetic patients is associated with aberrant expression of tear proteins, and the findings could lead to identification of novel pathways for therapeutic targeting and new diagnostic markers.


Population genetics of GYPB and association study between GYPB*S/s polymorphism and susceptibility to P. falciparum infection in the Brazilian Amazon.
Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil. Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection. GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity. Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population.


Being in the room: reflections on pregnancy options counseling during abortion training.
The Residency Review Committee requires that family medicine residents learn options counseling for women with unintended pregnancies. This qualitative study identifies important domains for future formal evaluations of pregnancy options counseling by exploring the relevant benefits reported by residents who underwent routine abortion training. To our knowledge, this is the first study of abortion training in family medicine to include an in-depth examination of its benefits in areas that may be important for pregnancy options counseling. Residents from two urban family medicine residency programs received training in first-trimester aspiration abortion at a high-volume abortion clinic during a routine women's health rotation. Thirty-minute semi-structured interviews were conducted with all 28 residents who rotated between July 2005 and November 2006. A coding scheme was developed and applied to transcripts for analysis. Through exposure to routine abortion training, residents reported improved knowledge, attitudes, and skills that are likely to be important for providing open and informed pregnancy options counseling. These include an understanding of the context of women's lives when they seek abortion care, familiarity with the procedure, and improved self-reported pregnancy options counseling skills. Our findings suggest that exposure to abortion training benefits residents in areas that may be important for providing effective pregnancy options counseling. In addition, residents' reflections on their involvement with patients during the abortion process highlight key domains for future formal evaluations of accurate and nonjudgmental options counseling for unintended pregnancy.


IL-33 expands suppressive CD11b+ Gr-1(int) and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival.
IL-33 administration is associated with facilitation of Th2 responses and cardioprotective properties in rodent models. However, in heart transplantation, the mechanism by which IL-33, signaling through ST2L (the membrane-bound form of ST2), promotes transplant survival is unclear. We report that IL-33 administration, while facilitating Th2 responses, also increases immunoregulatory myeloid cells and CD4(+) Foxp3(+) regulatory T cells (Tregs) in mice. IL-33 expands functional myeloid-derived suppressor cells, CD11b(+) cells that exhibit intermediate (int) levels of Gr-1 and potent T cell suppressive function. Furthermore, IL-33 administration causes an St2-dependent expansion of suppressive CD4(+) Foxp3(+) Tregs, including an ST2L(+) population. IL-33 monotherapy after fully allogeneic mouse heart transplantation resulted in significant graft prolongation associated with increased Th2-type responses and decreased systemic CD8(+) IFN-γ(+) cells. Also, despite reducing overall CD3(+) cell infiltration of the graft, IL-33 administration markedly increased intragraft Foxp3(+) cells. Whereas control graft recipients displayed increases in systemic CD11b(+) Gr-1(hi) cells, IL-33-treated recipients exhibited increased CD11b(+) Gr-1(int) cells. Enhanced ST2 expression was observed in the myocardium and endothelium of rejecting allografts, however the therapeutic effect of IL-33 required recipient St2 expression and was dependent on Tregs. These findings reveal a new immunoregulatory property of IL-33. Specifically, in addition to supporting Th2 responses, IL-33 facilitates regulatory cells, particularly functional CD4(+) Foxp3(+) Tregs that underlie IL-33-mediated cardiac allograft survival.


Diffractive axicons in oblique illumination: analysis and experiments and comparison with elliptical axicons.
Axicons in oblique illumination produce broadened focal lines, a problem, e.g., in scanning applications. A compact mathematical description of the focal segment is presented, for the first time, to our knowledge, and the results are compared with elliptical axicons in normal illumination. In both cases, analytical expressions in the form of asteroid curves are obtained from asymptotic wave theory and caustic surfaces. The results are confirmed by direct diffraction simulations and by experiments. In addition we show that at a fixed angle an elliptical axicon can be used to compensate for the adverse effects of oblique illumination.


Epidermal diseases in bottlenose dolphins: impacts of natural and anthropogenic factors.
Experimental studies have highlighted the potential influence of contaminants on marine mammal immune function and anthropogenic contaminants are commonly believed to influence the development of diseases observed in the wild. However, estimates of the impact of contaminants on wild populations are constrained by uncertainty over natural variation in disease patterns under different environmental conditions. We used photographic techniques to compare levels of epidermal disease in ten coastal populations of bottlenose dolphins (Tursiops truncatus) exposed to a wide range of natural and anthropogenic conditions. Epidermal lesions were common in all populations (affecting > 60% of individuals), but both the prevalence and severity of 15 lesion categories varied between populations. No relationships were found between epidermal disease and contaminant levels across the four populations for which toxicological data were available. In contrast, there were highly significant linear relationships with oceanographic variables. In particular, populations from areas of low water temperature and low salinity exhibited higher lesion prevalence and severity. Such conditions may impact on epidermal integrity or produce more general physiological stress, potentially making animals more vulnerable to natural infections or anthropogenic factors. These results show that variations in natural environmental factors must be accounted for when investigating the importance of anthropogenic impacts on disease in wild marine mammals.


Development and application of genetic probes for detection of Enterocytozoon bieneusi in formalin-fixed stools and in intestinal biopsy specimens from infected patients.
The microsporidium Enterocytozoon bieneusi is closely linked to wasting and diarrhea in a high proportion of individuals with AIDS. However, its relative contribution to disease is uncertain because diagnosis until recently depended on procedures involving endoscopy. A sensitive PCR technique which amplifies a fragment of the small-subunit rRNA gene of E. bieneusi from formalin-fixed stool samples was developed. Of 80 formalin-fixed stool samples collected from 74 Zimbabweans and 6 U.S. patients who were human immunodeficiency virus positive, 50% tested positive for E. bieneusi by PCR, whereas 24% tested positive for E. bieneusi by light microscopy of trichrome-stained fecal smears. In addition, we describe an in situ hybridization technique which detected and identified E. bieneusi as the causative agent in all six intestinal biopsy specimens tested. Both the PCR and in situ hybridization procedures are sensitive diagnostic tools which will complement currently available techniques and enable the differentiation of E. bieneusi from other microsporidia to be made.


Chemotherapy and radiotherapy in locally advanced head and neck cancer: an individual patient data network meta-analysis.
Randomised, controlled trials and meta-analyses have shown the survival benefit of concomitant chemoradiotherapy or hyperfractionated radiotherapy in the treatment of locally advanced head and neck cancer. However, the relative efficacy of these treatments is unknown. We aimed to determine whether one treatment was superior to the other. We did a frequentist network meta-analysis based on individual patient data of meta-analyses evaluating the role of chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC]) and of altered fractionation radiotherapy (Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck [MARCH]). Randomised, controlled trials that enrolled patients with non-metastatic head and neck squamous cell cancer between Jan 1, 1980, and Dec 31, 2016, were included. We used a two-step random-effects approach, and the log-rank test, stratified by trial to compare treatments, with locoregional therapy as the reference. Overall survival was the primary endpoint. The global Cochran Q statistic was used to assess homogeneity and consistency and P score to rank treatments (higher scores indicate more effective therapies). 115 randomised, controlled trials, which enrolled patients between Jan 1, 1980, and April 30, 2012, yielded 154 comparisons (28 978 patients with 19 253 deaths and 20 579 progression events). Treatments were grouped into 16 modalities, for which 35 types of direct comparisons were available. Median follow-up based on all trials was 6·6 years (IQR 5·0-9·4). Hyperfractionated radiotherapy with concomitant chemotherapy (HFCRT) was ranked as the best treatment for overall survival (P score 97%; hazard ratio 0·63 [95% CI 0·51-0·77] compared with locoregional therapy). The hazard ratio of HFCRT compared with locoregional therapy with concomitant chemoradiotherapy with platinum-based chemotherapy (CLRTP) was 0·82 (95% CI 0·66-1·01) for overall survival. The superiority of HFCRT was robust to sensitivity analyses. Three other modalities of treatment had a better P score, but not a significantly better HR, for overall survival than CLRTP (P score 78%): induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT; 89%), accelerated radiotherapy with concomitant chemotherapy (82%), and ICTaxPF followed by CLRT (80%). The results of this network meta-analysis suggest that further intensifying chemoradiotherapy, using HFCRT or ICTaxPF-CLRT, could improve outcomes over chemoradiotherapy for the treatment of locally advanced head and neck cancer. French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC.


Guidelines for breast and ovarian cancer genetic counseling referral: adoption and implementation in HMOs.
To describe referral guidelines for hereditary breast and ovarian cancer (HBOC) counseling among a group of Health Maintenance Organizations (HMOs) and awareness of such among primary care clinicians. An organizational assessment of plan policies and a primary care clinician survey. Five of the 7 HMOs reported having HBOC referral guidelines. Differences between plan's criteria included age of breast cancer onset, inclusion of male breast cancer, and second-degree relatives. Of the 91% clinicians responding, only half were aware of the HBOC guidelines. Awareness was higher in the plan with the most intense implementation effort (OR=3.0, 1.5-5.9) and among gynecologists (OR=2.8, 1.5-5.4). Although HBOC counseling guidelines within participating HMOs identify persons for referral that can be easily incorporated into routine practice, continued work is needed to better understand how to help primary care providers identify high-risk persons, and new models of providing genetic services may need to be considered.


Theoretical study of amplitude and phase filtering of guided waves.
The design of integrated optics filters by use of refinement software based on the Abelès thin-film computation method and the film mode matching method is studied. The results obtained with the two computation methods are compared. Good agreement is obtained provided that the fill factor of the guided mode in the component is high and that modal losses between waveguide sections are simulated by absorption with the Abelès computation method. Integrated optics devices that manage either the amplitude of guided waves such as a dense wavelength division multiplexing narrow-bandpass filter and a gain-flattening filter or the phase of guided waves such as a broadband dispersion compensator are


Migration of Implanon.
To determine whether or not migration of the Implanon rod does occur if correctly positioned and, if indeed migration does occur, to measure the degree of such migration. A prospective study of 100 women who requested and had Implanon rods inserted by one fully trained health care professional holding the Faculty of Family Planning and Reproductive Health Care Letter of Competence in Subdermal Contraceptive Implant Techniques. Measurements were made from the insertion site to the distal end of the rods at 3 and 12 months post-insertion. Of the 100 women studied, 95 were seen for follow-up at 3 months. There was no migration of Implanon in 58 (61%) patients. Of the remaining 37 (39%) patients where migration had occurred, 34 showed migration caudally and only three demonstrated cranial migration. With regard to the degree of migration, all but one case showed this to be less than 2 cm either cranially or caudally. At 1-year follow-up 87 patients were seen. No migration was noted in 39 (45%) patients. In the remaining 48 (55%) patients where migration had occurred, 44 showed migration caudally and only four demonstrated cranial migration, which in one case was over 2 cm. With regard to the degree of migration, all but one case showed this to be less than 2 cm either cranially or caudally. The measurement in the single case showing migration over 2 cm at 3 months remained the same at the 1-year follow-up. These results show that up to 1 year after insertion of Implanon significant migration of the rod does not occur. The degree of migration noted in all cases except one was less than 2 cm. Where migration was noted, in the majority of cases this occurred caudally towards the insertion site. There were no cases of deep migration.


Medical students' experiences of their own professional development during three clinical terms: a prospective follow-up study.
A modern competency-based medical education is well implemented globally, but less is known about how the included learning activities contribute to medical students' professional development. The aim of this study was to explore Swedish medical students' perceptions of the offered learning activities and their experiences of how these activities were connected to their professional development as defined by the CanMEDS framework. A prospective mixed method questionnaire study during three terms (internal medicine, scientific project, and surgery) in which data were collected by using contextual activity sampling system, i.e., the students were sent a questionnaire via their mobile phones every third week. All 136 medical students in the 6th of 11 terms in the autumn of 2012 were invited to participate. Seventy-four students (54%) filled in all of the required questionnaires (4 per term) for inclusion, the total number of questionnaires being 1335. The questionnaires focused on the students' experiences of learning activities, especially in relation to the CanMEDS Roles, collaboration with others and emotions (positive, negative, optimal experiences, i.e., "flow") related to the studies. The quantitative data was analysed statistically and, for the open-ended questions, manifest inductive content analysis was used. Three of the CanMEDs Roles, Medical Expert, Scholar, and Communicator, were most frequently reported while the four others, e.g., the role Health Advocate, were less common. Collaboration with students from other professions was most usual during the 8th term. Positive emotions and experience of "flow" were most often reported during clinical learning activities while the scientific project term was connected with more negative emotions. Our results showed that it is possible, even during clinical courses, to visualise the different areas of professional competence defined in the curriculum and connect these competences to the actual learning activities. Students halfway through their medical education considered the most important learning activities for their professional development to be connected with the Roles of Medical Expert, Scholar, and Communicator. Given that each of the CanMEDS Roles is at least moderately important during undergraduate medical education, the entire spectrum of the Roles should be emphasised and developed during the clinical years.


Selectively bred oysters can alter their biomineralization pathways, promoting resilience to environmental acidification.
Commercial shellfish aquaculture is vulnerable to the impacts of ocean acidification driven by increasing carbon dioxide (CO2 ) absorption by the ocean as well as to coastal acidification driven by land run off and rising sea level. These drivers of environmental acidification have deleterious effects on biomineralization. We investigated shell biomineralization of selectively bred and wild-type families of the Sydney rock oyster Saccostrea glomerata in a study of oysters being farmed in estuaries at aquaculture leases differing in environmental acidification. The contrasting estuarine pH regimes enabled us to determine the mechanisms of shell growth and the vulnerability of this species to contemporary environmental acidification. Determination of the source of carbon, the mechanism of carbon uptake and use of carbon in biomineral formation are key to understanding the vulnerability of shellfish aquaculture to contemporary and future environmental acidification. We, therefore, characterized the crystallography and carbon uptake in the shells of S. glomerata, resident in habitats subjected to coastal acidification, using high-resolution electron backscatter diffraction and carbon isotope analyses (as δ13 C). We show that oyster families selectively bred for fast growth and families selected for disease resistance can alter their mechanisms of calcite crystal biomineralization, promoting resilience to acidification. The responses of S. glomerata to acidification in their estuarine habitat provide key insights into mechanisms of mollusc shell growth under future climate change conditions. Importantly, we show that selective breeding in oysters is likely to be an important global mitigation strategy for sustainable shellfish aquaculture to withstand future climate-driven change to habitat acidification.


Challenges and options for animal and public health services in the next two decades.
Trade in livestock and livestock products makes up approximately one sixth of global agriculture trade. This trade is demand driven, primarily by growing human populations, changing economies, and consumer preferences in developing countries. Different rates of population growth, economic growth, urbanisation, environmental sustainability, and technology transfer will determine which countries will reap the greatest benefits. Global trends in demand and supply for food, not terrorism, will drive the future of animal and public health service delivery. To benefit the greatest number of people and countries, animal and public health services should support policies that temper growing disparities among rich and poor countries, city and rural populations, and the sexes. Economic growth is critical to overcoming disparities between countries and best supported by integrated animal health, public health, labour, and foreign policies. Opportunities for job growth will be the greatest along the value added chain of food production and will require significant investments in science- (risk-) based education.


Permuted tRNA genes in the nuclear and nucleomorph genomes of photosynthetic eukaryotes.
Transfer RNA (tRNA) is a central genetic element in the decoding of genome information for all of Earth's life forms. Nevertheless, there are a great number of missing tRNAs that have been left without examination, especially in microbial genomes. Two tRNA gene families remarkable in their structure and expression mechanism have been reported: split and permuted tRNAs. Split tRNAs in archaea are encoded on the genome as two or three fragmented genes and then processed into single tRNA molecules. Permuted tRNAs are organized with the 5' and 3' halves of the gene positioned in reverse on the genome and hitherto have been found only in one tiny red alga. Here we reveal a wide-ranging distribution of permuted tRNA genes in the genomes of photosynthetic eukaryotes. This includes in the smallest eukaryotic genome known to date, the nucleomorph genome of the chlorarachniophyte alga Bigelowiella natans. Comparison between cDNA and genomic DNA sequences of two nucleomorph-encoded tRNA(Ser) genes confirms that precursors are circularized and processed into mature tRNA molecules in vivo. In the tRNA(Ser)(AGA), adenine at the wobble position of the codon is likely modified to inosine to expand capacity of the codon recognition. We also show the presence of permuted tRNAs in the ultrasmall free-living green algae Ostreococcus and Micromonas, which are closely related to the B. natans nucleomorph. Conserved intron/leader sequence structures in the intron-containing and permuted tRNAs suggest the ancient origin of the splicing machinery in the common ancestor of eukaryotes and archaea. Meanwhile, a wide but patchy distribution of permuted tRNA genes in the photosynthetic eukaryotes implies that extant permuted tRNAs might have emerged multiple times. Taken together, our data demonstrate that permuted tRNA is an evolutionarily conserved and fundamental element in tiny eukaryotic genomes.


The prevalence of silent ischemia in Turkish patients with type 2 diabetes mellitus.
Cardiovascular disease (CVD) is the major cause of death in patients with type 2 diabetes mellitus. However, the diagnosis of CVD is delayed due to concealment of antecedent symptoms by factors such as autonomic neuropathy. In this study, we aimed to investigate the frequency of silent ischemia by using exercise electrocardiogram (ECG). The present study included 500 Turkish patients with type 2 diabetes (male/female: 222/278), who showed no evidence of CAD and angina pectoris or no sign(s) of ischemic changes in resting ECGs. All patients underwent treadmill exercise test according to Bruce protocol, and 62 cases (12.4%) exhibited abnormal changes. These patients identified by exercise ECG consisted of 28 males (28/222, [12.6%]) and 34 females (34/278, [12.2%]) and were then examined by coronary angiography. CAD was diagnosed in 53 individuals by coronary angiography. The abnormalities of exercise test are associated with the age of the patients or the duration of diabetes (p < 0.05). There is no significant difference in the severity of coronary disease or in the prevalence of silent ischemia between male and female patients. However, among the patients identified by exercise ECG females have higher body mass index than males, suggesting that obesity may represent the risk factor of CAD in women with type 2 diabetes.


Leakage does not fully offset soy supply-chain efforts to reduce deforestation in Brazil.
Zero-deforestation supply chain policies that leverage the market power of commodity buyers to change agricultural producer behavior can reduce forest clearing in regions with rapid commodity expansion and weak forest governance. Yet leakage-when deforestation is pushed to other regions-may dilute the global effectiveness of regionally successful policies. Here we show that domestic leakage offsets 43-50% of the avoided deforestation induced by existing and proposed zero-deforestation supply chain policies in Brazil's soy sector. However, cross-border leakage is insignificant (<3%) because soybean production is displaced to existing U.S. farmland. Eliminating deforestation from the supply chains of all firms exporting Brazilian soy to the EU or China from 2011-2016 could have reduced net global deforestation by 2% and Brazilian deforestation by 9%. Thus, if major tropical commodity importers (e.g., the EU) require traders to eliminate deforestation from their supply chains, it could help bend the curve on global forest loss.


Effects of a single bout of interval hypoxia on cardiorespiratory control and blood glucose in patients with type 2 diabetes.
Hypoxia may cause functional autonomic imbalance in diabetes. Intermittent hypoxia (IH), a technique improving the adaptation to hypoxia, might improve cardiorespiratory reflexes and, ultimately, blood glucose concentrations in patients with type 2 diabetes. We tested whether a single bout of IH could initiate a long-lasting response potentially leading to better adaptation to hypoxia. In 14 patients with type 2 diabetes without autonomic complications, we measured blood pressure, heart rate, oxygen saturation, chemoreflex (hypoxic and hypercapnic ventilatory responses, ventilatory recruitment threshold), and baroreflex sensitivity before, immediately after, and 3 and 6 h after a 1-h single bout of IH (6-min breathing of 13% oxygen mixture 5 times each separated by 6-min recovery). The measurements were repeated on a placebo day (at least 1 week apart, in random sequence) when subjects were only breathing room air (single-blind protocol). IH significantly increased hypercapnic ventilatory responses and reduced ventilatory recruitment threshold, and increased oxygen saturation and blood pressures, whereas increases in heart rate variability and baroreflex sensitivity were not significant. Blood glucose significantly decreased after IH. No such changes were observed during the placebo day, except an increase in oxygen saturation. Some of the effects lasted 3 h after IH, and some even persisted until 6 h after IH. A single bout of IH induced an initial adaptation to hypoxia, with improvement in cardiorespiratory reflexes and reduction in blood glucose. Patients with type 2 diabetes could potentially benefit from the application of a full (>2 weeks) IH intervention.


Impact of Noise in Operating Theater: A Surgeon's and Anesthesiologist's Perspective.
Noise is often considered as an undesirable sound. Excess noise is a health threat that deteriorates one's concentration and communication. Noise in the operating theater can be disturbing, impairs communication, and can lead to stress. The aim of this survey was to assimilate information about the perspective of surgeons and anesthesiologists regarding noise in the operating theater and whether it affects their work atmosphere. A questionnaire consisting of 15 closed-ended questions excluding one open-ended question was given to surgeons from various specialties and anesthesiologists. The subjective response were analyzed and documented. Data analysis was done using descriptive statistics. Association was found out using Chi-square test. We collected a total of 290 responses, of which 87.6% (n = 254) considered noise to increase the stress level and deteriorates the quality of teamwork (83.8%, n = 243). Noise affects communication among the staff (86.2%, n = 250) and decreases their concentration level (85.5%, n = 248) which could be harmful in view of the patient's safety. 87.9% (n = 255) of the participants were in favor of limiting the number of people in the operating theater. Nonetheless, 73% (n = 211) considered music has a calming effect and were in favor of music in the operating theater. Noise in the operating theater can have distressing effects on surgeons, jeopardizing the patient's safety. However, a flip side to this is that music is considered to have a calming and soothing effect decreasing the anxiety and stress levels.


Susceptibility of Cardiac Troponin Assays to Biotin Interference.
To investigate biotin interference on three cardiac troponin (cTn) assays and demonstrate a method to overcome biotin interference. cTn levels were measured in (1) plasma from healthy volunteers on 10-mg daily biotin supplementation mixed with a plasma with known elevated troponin, (2) plasmas with known elevated cTn after mixing in reagent biotin to simulate supplementation, and (3) biotin-spiked plasma specimens pretreated with streptavidin-agarose beads. Daily biotin ingestion (10 mg) and studies simulating daily biotin use resulted in significant interference in the Gen5 cardiac troponin T (cTnT) assay; the contemporary Gen 4 cTnT and high-sensitivity cardiac troponin I (hs-cTnI) assays were unaffected. The biotin interference threshold was 31, 315, and more than 2,000 ng/mL for Gen5 cTnT, cTnT, and hs-cTnI assays, respectively. Streptavidin pretreatment blocked biotin interference in cTn assays. Biotin interference is possible at plasma concentrations achievable by ingestion of over-the-counter supplements that may lead to delayed or missed diagnosis of myocardial injury with the Gen5 cTnT assay.


Extensive genomic characterization of a set of near-isogenic lines for heterotic QTL in maize (Zea mays L.).
Despite the crucial role that heterosis has played in crop improvement, its genetic and molecular bases are still elusive. Several types of structured populations were used to discover the genetic architecture underlying complex phenotypes, and several QTL related to heterosis were detected. However, such analyses generally lacked the statistical power required for the detailed characterization of individual QTL. Currently, QTL introgression into near-isogenic materials is considered the most effective strategy to this end, despite such materials inevitably contain a variable, unknown and undesired proportion of non-isogenic genome.An introgression program based on residual heterozygous lines allowed us to develop five pairs of maize (Zea mays L.) near-isogenic lines (NILs) suitable for the fine characterization of three major heterotic QTL previously detected. Here we describe the results of the detailed genomic characterization of these NILs that we undertook to establish their genotypic structure, to verify the presence of the expected genotypes within target QTL regions, and to determine the extent and location of residual non-isogenic genomic regions. The SNP genotyping approach allowed us to determine the parent-of-origin allele for 14,937 polymorphic SNPs and to describe in detail the genotypic structure of all NILs. The correct introgression was confirmed for all target QTL in the respective NIL and several non-isogenic regions were detected genome-wide. Possible linkage drag effects associated to the specific introgressed regions were observed. The extent and position of other non-isogenic regions varied among NIL pairs, probably deriving from random segregating sections still present at the separation of lineages within pairs. The results of this work strongly suggest that the actual isogenicity and the genotypic architecture of near-isogenic materials should be monitored both during the introgression procedure and on the final materials as a paramount requisite for a successful mendelization of target QTL. The information here gathered on the genotypic structure of NILs will be integrated in future experimental programs aimed at the fine mapping and isolation of major heterotic QTL, a crucial step towards the understanding of the molecular bases of heterosis in maize.


Atypical clinical manifestations of hepatitis a among children aged 1-16 years in South-Eastern Region of Turkey.
Yılmaz-Çiftdoğan D, Köse E, Aslan S, Gayyurhan E. Atypical clinical manifestations of hepatitis A among children aged 1-16 years in South-Eastern region of Turkey. Turk J Pediatr 2015; 57: 339-344. Hepatitis A virus (HAV) infection has several atypical manifestations, including fulminant hepatitis, relapsing hepatitis, prolonged cholestasis and extrahepatic manifestations. In this study, we aimed to describe the characteristics and outcomes of the pediatric patients with atypical manifestations of HAV infection. Four hundred twelve children with symptomatic hepatitis A infection admitted to Gaziantep Children`s Hospital Department of Pediatric Infectious Disease between August 2011 and January 2013 were analyzed retrospectively. Atypical presentations were present in 53 (12.8%) children of 412 children with HAV infection. Patients with atypical presentations (8.3±3.7 years) were older than patients with typical presentations (5.9±3.1 years) (p=0.001). Children with atypical features of hepatitis A statistically had higher initial and peak values of alanine aminotransferase (ALT), aspartate aminotransferase (AST), international normalized ratio (INR), serum total and direct bilirubin than typical manifested group. We can conclude that older age is the major risk factor for atypical presentation of HAV infections. Higher initial and peak levels of AST, ALT, INR, total and direct bilirubin could predict the atypical manifestation.


Should all patients undergoing cardiac catheterization or percutaneous transluminal coronary angioplasty receive oxygen?
Supplemental oxygen is routinely administered to patients with acute coronary syndromes. The risk of significant morbidity during cardiac catheterization or coronary angioplasty has been well described; however, to our knowledge, the need for routine oxygen supplementation in these patients has not been investigated. In phase 1, we prospectively studied 142 patients undergoing diagnostic cardiac catheterization (n = 94) or percutaneous transluminal coronary angioplasty (PTCA) (n = 48) to determine the incidence of procedure-related hypoxemia (pulse oximetry derived oxygen saturation [SpO2] < 90 percent of > 1 min duration) while breathing room air (RA). In phase 2, 134 patients undergoing diagnostic cardiac catheterization (n = 78) or PTCA (n = 56) were randomly allocated to breathe either RA or supplemental oxygen (O2, 6 L/min by nasal cannula) to determine the effect of oxygen administration on procedure-related hypoxemia. Oximetry results were compared with pertinent clinical and procedural data that might predispose patients to develop hypoxemia. Phase 1--Moderate to severe hypoxemia occurred in 36 percent (34/94) of patients undergoing diagnostic catheterization and in 56 percent (27/48) of patients undergoing PTCA. In the diagnostic catheterization group, there were a total of 25 episodes of moderate hypoxemia (SpO2 85 to 89 percent) lasting 4.0 +/- 4.3 min and 11 episodes of severe hypoxemia (SpO2 < 85 percent) of greater duration, 11.7 +/- 7.5 min (p < 0.008). In the PTCA group, there were 24 episodes of moderate hypoxemia and six episodes of severe hypoxemia lasting 4.8 +/- 4.3 min and 8.2 +/- 3.8 min, respectively. A history of chronic lung disease was associated with hypoxemia (p < 0.05) in the diagnostic group. In addition, 11 patients undergoing diagnostic catheterization who had baseline SpO2 < 95 percent all developed hypoxemia during the procedure. In this subset of patients, there was a higher incidence of cigarette smoking (p = 0.02), chronic lung disease (p = 0.04), higher left ventricular diastolic pressure (p = 0.02), and lower ejection fraction (p = 0.002) when compared with the 83 remaining patients undergoing diagnostic catheterization with a baseline SpO2 > 95 percent. Phase 2--Oxygen therapy was associated with a reduction in the incidence of hypoxemia from 42 percent to 5 percent (RA vs O2, p < 0.001) in the diagnostic catheterization group and 39 percent to 11 percent (RA vs O2, p < 0.03) in the PTCA group. Significant hypoxemia is a common finding among patients undergoing cardiac catheterization or angioplasty despite the absence of predictive risk factors. Severe and prolonged hypoxemic episodes occurred in 10 percent (14/142, phase 1) of patients breathing room air. Patients undergoing diagnostic catheterization with history of chronic lung disease or a baseline SpO2 < 95 percent are at high risk to develop moderate-severe hypoxemia. Oxygen therapy significantly reduced the incidence and severity of procedure-induced hypoxemia in both groups. Our data support the use of both pulse oximetry and oxygen supplementation in patients undergoing cardiac catheterization and PTCA.


Decision-making styles and physiological correlates of negative stress: is there a relation?
There are 5 independent, although not mutually exclusive, styles used by military officers when making decisions: rational, intuitive, dependent, avoidant, and spontaneous (Scott & Bruce, 1995). The rational and intuitive styles are part of the cognitive style concept, whereas the conceptual foundation of the remaining 3 styles is less clear. The dependent and the avoidant styles were expected to be accompanied by increased levels of negative stress, while this was not expected of the remaining 3 styles. This hypothesis was put to test. Twenty-three male Swedish Army majors were asked to make decisions in 2 different military situations. Their decision styles were measured by the General Decision Making Style inventory (GDMS; Scott & Bruce, 1995). Saliva cortisol release indicated negative stress and was measured on 4 occasions: twice before, after the first decision, and after the second decision. The avoidant style was related to negative stress, as predicted. There was, however, no difference between the base-line measurements and the after-decision measurements, suggesting that officers with an avoidant decision style may, in general, have higher levels of cortisol secretion (i.e., being more of the worrying kind).


Certolizumab pegol in combination with dose-optimised methotrexate in DMARD-naïve patients with early, active rheumatoid arthritis with poor prognostic factors: 1-year results from C-EARLY, a randomised, double-blind, placebo-controlled phase III study.
To assess the efficacy and safety of certolizumab pegol (CZP)+dose-optimised methotrexate (MTX) versus placebo (PBO)+dose-optimised MTX in inducing and sustaining clinical remission in DMARD-naïve patients with moderate-to-severe, active, progressive rheumatoid arthritis (RA), with poor prognostic factors over 52 weeks. DMARD-naïve patients with ≤1 year of active RA were randomised (3:1) in a double-blind manner to CZP (400 mg Weeks 0, 2, 4, then 200 mg Q2W to Week 52)+MTX or PBO+MTX (the mean optimised-MTX dose=21 and 22 mg/week, respectively). Sustained remission (sREM) and sustained low disease activity (sLDA; DAS28(ESR)<2.6 and DAS28(ESR)≤3.2, respectively, at both Weeks 40 and 52) were the primary and secondary endpoints. Patients were randomised to CZP+MTX (n=660) and PBO+MTX (n=219). At Week 52, significantly more patients assigned to CZP+MTX compared with PBO+MTX achieved sREM (28.9% vs 15.0%, p<0.001) and sLDA (43.8% vs 28.6%, p<0.001). Inhibition of radiographic progression and improvements in physical functioning were significantly greater for CZP+MTX versus PBO+MTX (van der Heijde modified total Sharp score (mTSS) mean absolute change from baseline (CFB): 0.2 vs 1.8, p<0.001, rate of mTSS non-progressors: 70.3% vs 49.7%, p<0.001; least squares (LS) mean CFB in Health Assessment Questionnaire-Disability Index (HAQ-DI): -1.00 vs -0.82, p<0.001). Incidence of adverse events (AEs) and serious AEs was similar between treatment groups. Infection was the most frequent AE, with higher incidence for CZP+MTX (71.8/100 patient-years (PY)) versus PBO+MTX (52.7/100 PY); the rate of serious infection was similar between CZP+MTX (3.3/100 PY) and PBO+MTX (3.7/100 PY). CZP+dose-optimised MTX treatment of DMARD-naïve early RA resulted in significantly more patients achieving sREM and sLDA, improved physical function and inhibited structural damage compared with PBO+dose-optimised MTX. NCT01519791.


Work in the family and employing organization.
Issues involved in the attempts to balance roles in employing organizations and family organizations are discussed. The literature on the causal links between work and family relationships, the variables used in such studies, and the models used to describe the findings are presented. Because attempts to balance the roles in the two environments can lead to conflict and stress, organizations have responded with programs such as maternity and parental leave, child and dependent care, alternative work schedules and work stations, and employee assistance and relocation programs. These programs are reviewed with particular emphasis on their benefits and costs.


Household-wide ivermectin treatment for head lice in an impoverished community: randomized observer-blinded controlled trial.
To generate evidence on the effectiveness of household-wide treatment for preventing the transmission of pediculosis capitis (head lice) in resource-poor communities. We studied 132 children without head lice who lived in a slum in north-eastern Brazil. We randomized the households of the study participants into an intervention and a control group and prospectively calculated the incidence of infestation with head lice among the children in each group. In the intervention group, all of the children's family members who lived in the household were treated with ivermectin; in the control group, no family member was treated. We used the chi(2) test with continuity correction or Fisher's exact test to compare proportions. We performed survival analysis using Kaplan-Meier estimates with log rank testing and the Mann-Whitney U test to analyse the length of lice-free periods among sentinel children, and we used Cox regression to analyse survival data on a multivariate level. We also carried out a subgroup analysis based on gender. Children in the intervention group remained free from infestation with head lice significantly longer than children in the control group. The median infestation-free period in the intervention group was 24 days (interquartile range, IQR: 11-45), as compared to 14 days (IQR: 11-25) in the control group (P = 0.01). Household-wide treatment with ivermectin proved significantly more effective among boys than among girls (P = 0.005). After treatment with ivermectin, the estimated number of annual episodes of head lice infestation was reduced from 19 to 14 in girls and from 15 to 5 in boys. Female sex and extreme poverty were independent risk factors associated with a shortened disease-free period. In an impoverished community, girls and the poorest of the poor are the population groups that are most vulnerable for head lice infestation. To decrease the number of head lice episodes per unit of time, control measures should include the treatment of all household contacts. Mass treatment with ivermectin may reduce the incidence of head lice infestation and associated morbidity in resource-poor communities.


A Combined Linkage and Exome Sequencing Analysis for Electrocardiogram Parameters in the Erasmus Rucphen Family Study.
Electrocardiogram (ECG) measurements play a key role in the diagnosis and prediction of cardiac arrhythmias and sudden cardiac death. ECG parameters, such as the PR, QRS, and QT intervals, are known to be heritable and genome-wide association studies of these phenotypes have been successful in identifying common variants; however, a large proportion of the genetic variability of these traits remains to be elucidated. The aim of this study was to discover loci potentially harboring rare variants utilizing variance component linkage analysis in 1547 individuals from a large family-based study, the Erasmus Rucphen Family Study (ERF). Linked regions were further explored using exome sequencing. Five suggestive linkage peaks were identified: two for QT interval (1q24, LOD = 2.63; 2q34, LOD = 2.05), one for QRS interval (1p35, LOD = 2.52) and two for PR interval (9p22, LOD = 2.20; 14q11, LOD = 2.29). Fine-mapping using exome sequence data identified a C > G missense variant (c.713C > G, p.Ser238Cys) in the FCRL2 gene associated with QT (rs74608430; P = 2.8 × 10-4, minor allele frequency = 0.019). Heritability analysis demonstrated that the SNP explained 2.42% of the trait's genetic variability in ERF (P = 0.02). Pathway analysis suggested that the gene is involved in cytosolic Ca2+ levels (P = 3.3 × 10-3) and AMPK stimulated fatty acid oxidation in muscle (P = 4.1 × 10-3). Look-ups in bioinformatics resources showed that expression of FCRL2 is associated with ARHGAP24 and SETBP1 expression. This finding was not replicated in the Rotterdam study. Combining the bioinformatics information with the association and linkage analyses, FCRL2 emerges as a strong candidate gene for QT interval.


Association between medical home enrollment and health care utilization and costs among breast cancer patients in a state Medicaid program.
The patient-centered medical home (PCMH) is increasingly being implemented in an effort to improve and coordinate primary care, but its effect on health care utilization among breast cancer patients remains unclear. The objective of this study was to examine health care utilization and expenditures as a function of PCMH enrollment among breast cancer patients in North Carolina's Medicaid program. North Carolina Medicaid claims linked to North Carolina Central Cancer Registry records (2003-2007) were used to examine monthly patterns of health care use and expenditures. Controlling for a selection bias for time-invariant characteristics, fixed effects regression models analyzed associations between PCMH enrollment and utilization of outpatient, inpatient, and emergency department (ED) services and Medicaid expenditures during the 15 months after the diagnosis of breast cancer. Among 758 breast cancer patients, 381 (50%) were enrolled in a PCMH at some time in the 15 months after diagnosis. After controlling for individual fixed effects, PCMH enrollment was significantly associated with greater outpatient service use, but there was no difference in the probability of inpatient hospitalizations or ED visits. Enrollment in a PCMH was associated with increased average expenditures of $429 per month during the first 15 months. Greater outpatient care utilization and increased average expenditures among breast cancer patients enrolled in a PCMH may suggest that these women have improved access to primary and specialty care. Expanding PCMHs may change patterns of service utilization for Medicaid breast cancer patients but may not be associated with lower costs.


Comparative genomics of two Leptospira interrogans serovars reveals novel insights into physiology and pathogenesis.
Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing of Leptospira interrogans serovar Copenhageni and comparative analysis with the available Leptospira interrogans serovar Lai genome reveal that despite overall genetic similarity there are significant structural differences, including a large chromosomal inversion and extensive variation in the number and distribution of insertion sequence elements. Genome sequence analysis elucidates many of the novel aspects of leptospiral physiology relating to energy metabolism, oxygen tolerance, two-component signal transduction systems, and mechanisms of pathogenesis. A broad array of transcriptional regulation proteins and two new families of afimbrial adhesins which contribute to host tissue colonization in the early steps of infection were identified. Differences in genes involved in the biosynthesis of lipopolysaccharide O side chains between the Copenhageni and Lai serovars were identified, offering an important starting point for the elucidation of the organism's complex polysaccharide surface antigens. Differences in adhesins and in lipopolysaccharide might be associated with the adaptation of serovars Copenhageni and Lai to different animal hosts. Hundreds of genes encoding surface-exposed lipoproteins and transmembrane outer membrane proteins were identified as candidates for development of vaccines for the prevention of leptospirosis.


Chromatin exposes intrinsic differences in the transcriptional activities of estrogen receptors alpha and beta.
The biological actions of estrogens are mediated via two distinct intranuclear estrogen receptor (ER) proteins, ERalpha and ERbeta. We have used an in vitro chromatin assembly and transcription system to compare the transcriptional activities of the two ERs in the context of chromatin, the physiological template for transcription by RNA polymerase II. We find that under conditions where many biochemical activities of the receptors are similar (e.g. ligand binding, chromatin binding, chromatin remodeling and co-activator recruitment), liganded ERalpha is a much more potent transcriptional activator than ERbeta with chromatin templates, but not with naked DNA. This difference is attributable to the N-terminal A/B region of ERalpha, which contains a transferable activation function that facilitates transcription specifically with chromatin templates. Interestingly, chromatin selectively restricts ligand-dependent transcriptional activation by ERbeta under some conditions (e.g. with a closed chromatin architecture), while allowing it under other conditions (e.g. with an open chromatin architecture). Collectively, our results define an important role for chromatin in determining signaling outcomes mediated by distinct subtypes of signal-transducing transcriptional activator proteins.


Resuscitation research: future directions and ethical issues.
Cardiopulmonary resuscitation research is a vital area of research that has made significant contributions to medical care over the last several decades. Abundant information currently exists in the medical literature, as a result of research in the areas of cardiac arrest and outcomes, physiology of cardiac arrest, pharmacologic treatments, mechanical interventions, and societal and ethical issues. Despite numerous clinical trials demonstrating physiologic benefit of various interventions, few interventions have had as much impact on outcomes of cardiac arrest as have improvements in out-of-hospital response times and rapid availability of medical treatment. Although abundant information exists regarding physiologic aspects of resuscitation, relatively little information exists about ethical, psychological, and social aspects of resuscitation. In addition to attempts to improve outcomes of cardiac arrest, researchers should also strive to improve the experiences of patients and families involved. These realities provide future strategies and directions for the best use of resuscitation research resources; although physiologic and pharmacologic research will always have significant roles in the improvement of medical care, the rapid delivery of out-of-hospital care and ethical issues will be indispensable areas of research focus in the future.


Delta-Notch signalling in segmentation.
Modular body organization is found widely across multicellular organisms, and some of them form repetitive modular structures via the process of segmentation. It's vastly interesting to understand how these regularly repeated structures are robustly generated from the underlying noise in biomolecular interactions. Recent studies from arthropods reveal similarities in segmentation mechanisms with vertebrates, and raise the possibility that the three phylogenetic clades, annelids, arthropods and chordates, might share homology in this process from a bilaterian ancestor. Here, we discuss vertebrate segmentation with particular emphasis on the role of the Notch intercellular signalling pathway. We introduce vertebrate segmentation and Notch signalling, pointing out historical milestones, then describe existing models for the Notch pathway in the synchronization of noisy neighbouring oscillators, and a new role in the modulation of gene expression wave patterns. We ask what functions Notch signalling may have in arthropod segmentation and explore the relationship between Notch-mediated lateral inhibition and synchronization. Finally, we propose open questions and technical challenges to guide future investigations into Notch signalling in segmentation.


Evaluating psychiatric readmissions in the emergency department of a large public hospital.
Hospital emergency departments (EDs) around the country are being challenged by an ever-increasing volume of patients seeking psychiatric services. This manuscript describes a study performed to identify internal and external factors contributing to repeated psychiatric patient admissions to the hospital main ED. Data from ED visits of patients who were admitted to the Parkland Memorial Hospital ED (the community hospital for Dallas County, TX, USA) with a psychiatric complaint more than once within a 30-day period were evaluated (n=202). A 50-item readmission survey was used to collect information on demographic and clinical factors associated with 30-day readmission, as well as to identify quality improvement opportunities by assessing related moderating factors. An analysis of acute readmission visits (occurring within 3 days of previous discharge) was also performed. Patients readmitted to the ED commonly present with a combination of acute psychiatric symptoms, substance use (especially in the case of acute readmission), and violent or suicidal behavior. The vast majority of cases reviewed found that readmitted patients had difficulties coordinating care outside the ED. A number of moderating factors were identified and targeted for quality improvement including additional support for filling prescriptions, transportation, communication with family and outside providers, drug and alcohol treatment, intensive case management, and housing. Many of the resources necessary to reduce psychiatric patient visits to hospital EDs are available within the community. There is no formal method of integrating and insuring the continuity of community services that may reduce the demand for psychiatric and related services in the ED. While agreements between community service providers may be challenging and require considerable vigilance to maintain equitable agreements between parties, this route of improving efficiency may be the only available method, given the current and projected patient care needs.


Superlattice-based thin-film thermoelectric modules with high cooling fluxes.
In present-day high-performance electronic components, the generated heat loads result in unacceptably high junction temperatures and reduced component lifetimes. Thermoelectric modules can, in principle, enhance heat removal and reduce the temperatures of such electronic devices. However, state-of-the-art bulk thermoelectric modules have a maximum cooling flux qmax of only about 10 W cm(-2), while state-of-the art commercial thin-film modules have a qmax <100 W cm(-2). Such flux values are insufficient for thermal management of modern high-power devices. Here we show that cooling fluxes of 258 W cm(-2) can be achieved in thin-film Bi2Te3-based superlattice thermoelectric modules. These devices utilize a p-type Sb2Te3/Bi2Te3 superlattice and n-type δ-doped Bi2Te3-xSex, both of which are grown heteroepitaxially using metalorganic chemical vapour deposition. We anticipate that the demonstration of these high-cooling-flux modules will have far-reaching impacts in diverse applications, such as advanced computer processors, radio-frequency power devices, quantum cascade lasers and DNA micro-arrays.


Fatalities in poisoned patients managed by medical toxicologists.
Background: Poisoning is a leading cause of injury-related death in the United States. The Toxicology Investigators Consortium (ToxIC) Case Registry, established by the American College of Medical Toxicology, prospectively captures patients who were directly cared for and managed at the bedside by medical toxicology services. We sought to describe exposure cases who presented to Emergency Departments (EDs) across ToxIC sites, received direct bedside care by medical toxicologists; however, the intoxication resulted in fatality.Methods: We identified all cases in the ToxIC Case Registry that resulted in fatality after hospital presentation over the 6-year study period. We collected data on patient demographics and clinical information including age group, sex, circumstances of exposure, route of exposure, substances involved, presenting signs and symptoms and management prior to death.Results: Of 44,567 recorded cases in the registry over the study period, 268 (0.6%) fatalities met the inclusion criteria and comprise the study cohort. There was no sex predominance (138 females; 51.5%) and 27 (10.1%) were pediatric fatalities. In 195 (72.7%) patients, exposure was intentional. In 175 (65.3%) patients, fatality was associated with exposure to pharmaceuticals. The leading substances resulting in death were non-opioid analgesics, followed by opioids (72% prescription opioids), cardiovascular medications, sedatives, antipsychotics, antidepressants, and sympathomimetics. At time of consult, the central nervous system was the most common system affected in both fatal and non-fatal cases. Compared with non-fatal ToxIC cases (n = 44,299), fatal cases involved significantly less children (27.7% vs. 10.1%, respectively; p < .001), and were managed more aggressively (e.g., mechanical ventilation 8.3% vs. 69.8%, p < .001). Both non-opioid analgesics (25.3% vs. 14.7%; p < .001) and opioids (17.8% vs. 7.5%; p < .001) were significantly more likely to be ingested in fatal compared with non-fatal cases, although analgesics, opioids, and non-opioids, were the most common agents implicated in both groups.Conclusions: Most ToxIC registry exposures resulting in death involve intentional exposure, without sex predominance. One in 10 fatalities involved a child. Analgesics, non-opioids, and opioids are the most commonly implicated agents in both fatal and non-fatal intoxications, which highlights the centrality of these agents as major sources of both morbidity and mortality.


"Make Sure Somebody Will Survive from This": Transformative Practices of Hope among Danish Organ Donor Families.
Based on anthropological fieldwork among Danish organ donor families and hospital staff in neurointensive care units, this article explores the transformative practices of hope in Danish organ donation. Focusing on various phases of the organ donation process, I demonstrate how families and professionals practice hope in astounding ways: when hoping for organs, when hoping for the end of patient suffering, when hoping for the usability of the donor body, and when hoping to help future donor families by sharing painful experiences. By focusing on such practices and transformations of hope, this article sheds light on the social negotiations of life and death among families and staffs in medical contexts and describes how the dignity of the deceased donor and the usability of the donor body are closely connected in family attempts to make donation decisions meaningful during and after a tragic death.


Survey response inducements for registered nurses.
The past 20 years have seen an overall decline in survey response rates and an even more pronounced decline in samples of health care professionals. The authors tested the use of a "thank you" or "reminder" postcard as a method by which to stem the tide of declining response rates. The authors conducted a mail and telephone survey of 49,605 registered nurses for the 2000 National Sample Survey of Registered Nurses and sent an extra mailing to a random subsample (n = 4,968). They then compared response rates for both groups. Contrary to prior research, this study found that reminder postcards did not improve response rates or rates of return. There may be several reasons for this finding, including the general familiarity with, and high saliency of, this research project for the nursing community. These results suggest that even widely accepted best practices for survey methods deserve scrutiny when applied to special subpopulations.


A critical review of food-associated factors proposed in the etiology of feline hyperthyroidism.
Since the first description of feline hyperthyroidism (HT) in 1979, several studies have been undertaken to define the etiology of the disease. Epidemiologic studies, after investigating non-food- and food-associated factors, suggest a multifactorial etiology. However, in the absence of prospective cohort studies that can confirm a cause-and-effect relationship between HT and associated risk factors, no causative factor for HT has been identified to date. Feline HT resembles toxic nodular goiter in humans, with autonomously functioning upregulated iodide uptake systems. Contribution of the diet to HT development remains controversial. The purpose of this paper is to review critically the reported food-associated risk factors for HT.


Genotet: An Interactive Web-based Visual Exploration Framework to Support Validation of Gene Regulatory Networks.
Elucidation of transcriptional regulatory networks (TRNs) is a fundamental goal in biology, and one of the most important components of TRNs are transcription factors (TFs), proteins that specifically bind to gene promoter and enhancer regions to alter target gene expression patterns. Advances in genomic technologies as well as advances in computational biology have led to multiple large regulatory network models (directed networks) each with a large corpus of supporting data and gene-annotation. There are multiple possible biological motivations for exploring large regulatory network models, including: validating TF-target gene relationships, figuring out co-regulation patterns, and exploring the coordination of cell processes in response to changes in cell state or environment. Here we focus on queries aimed at validating regulatory network models, and on coordinating visualization of primary data and directed weighted gene regulatory networks. The large size of both the network models and the primary data can make such coordinated queries cumbersome with existing tools and, in particular, inhibits the sharing of results between collaborators. In this work, we develop and demonstrate a web-based framework for coordinating visualization and exploration of expression data (RNA-seq, microarray), network models and gene-binding data (ChIP-seq). Using specialized data structures and multiple coordinated views, we design an efficient querying model to support interactive analysis of the data. Finally, we show the effectiveness of our framework through case studies for the mouse immune system (a dataset focused on a subset of key cellular functions) and a model bacteria (a small genome with high data-completeness).


Effects of radiofrequency electromagnetic fields (UMTS) on reproduction and development of mice: a multi-generation study.
Male and female mice (C57BL) were chronically exposed (life-long, 24 h/day) to mobile phone communication electromagnetic fields at approximately 1966 MHz (UMTS). Their development and fertility were monitored over four generations by investigating histological, physiological, reproductive and behavioral functions. The mean whole-body SARs, calculated for adult animals at the time of mating, were 0 (sham), 0.08, 0.4 and 1.3 W/kg. Power densities were kept constant for each group (0, 1.35, 6.8 and 22 W/m(2)), resulting in varying SARs due to the different numbers of adults and pups over the course of the experiment. The experiment was done in a blind fashion. The results show no harmful effects of exposure on the fertility and development of the animals. The number and the development of pups were not affected by exposure. Some data, albeit without a clear dose-response relationship, indicate effects of exposure on food consumption that is in accordance with some data published previously. In summary, the results of this study do not indicate harmful effects of long-term exposure of mice to UMTS over several generations.


Combined treatment with renin-angiotensin system blockers and polyunsaturated fatty acids in proteinuric IgA nephropathy: a randomized controlled trial.
Currently, several therapeutic protocols exist for IgA nephropathy (IgAN); results in slowing the progression to end-stage renal disease (ESRD) are variable, but approximately 30-40% of patients require replacement therapy (dialysis or renal transplantation) by 20 years from the onset. The adverse effects brought by the chronic assumption of drugs can be a potential limit. Actually, the most used therapies for IgAN are renin-angiotensin system blockers (RASB), glucocorticoids and immunosuppressive agents. Trials with polyunsaturated fatty acids (PUFA) in IgAN have been done since the first successful attempt by Hamazaki in 1984, resulting in alternate answers, but no trials have ever been done testing the efficacy of combined therapy with RASB and PUFA. We tested the effect of a 6-month course of PUFA (3 grams/day) in a group of 30 patients with biopsy-proven IgAN and proteinuria already treated with RASB randomized to receive PUFA supplementation or to continue their standard therapy. The primary end-point was the percent reduction of proteinuria from the baseline. Secondary end-points were modifications in glomerular filtration rate (GFR), blood pressure, serum triglycerides and erythrocyturia. At the end of the 6-month trial, the percent reduction of proteinuria was 72.9% in the PUFA group and 11.3% in the RASB group (P < 0.001). A reduction of >or=50% of baseline proteinuria was achieved in 80.0% of PUFA patients and 20.0% of RASB patients (P = 0.002). Erythrocyturia was significantly lower in the PUFA group (P = 0.031). No significant changes in renal function, blood pressure and triglycerides were observed. PUFA associated with RASB reduced proteinuria in patients with IgAN more than RASB alone.


Mechanisms of reflex bladder activation by pudendal afferents.
Activation of pudendal afferents can evoke bladder contraction or relaxation dependent on the frequency of stimulation, but the mechanisms of reflex bladder excitation evoked by pudendal afferent stimulation are unknown. The objective of this study was to determine the contributions of sympathetic and parasympathetic mechanisms to bladder contractions evoked by stimulation of the dorsal nerve of the penis (DNP) in α-chloralose anesthetized adult male cats. Bladder contractions were evoked by DNP stimulation only above a bladder volume threshold equal to 73 ± 12% of the distension-evoked reflex contraction volume threshold. Bilateral hypogastric nerve transection (to eliminate sympathetic innervation of the bladder) or administration of propranolol (a β-adrenergic antagonist) decreased the stimulation-evoked and distension-evoked volume thresholds by -25% to -39%. Neither hypogastric nerve transection nor propranolol affected contraction magnitude, and robust bladder contractions were still evoked by stimulation at volume thresholds below the distension-evoked volume threshold. As well, inhibition of distention-evoked reflex bladder contractions by 10 Hz stimulation of the DNP was preserved following bilateral hypogastric nerve transection. Administration of phentolamine (an α-adrenergic antagonist) increased stimulation-evoked and distension-evoked volume thresholds by 18%, but again, robust contractions were still evoked by stimulation at volumes below the distension-evoked threshold. These results indicate that sympathetic mechanisms contribute to establishing the volume dependence of reflex contractions but are not critical to the excitatory pudendal to bladder reflex. A strong correlation between the magnitude of stimulation-evoked bladder contractions and bladder volume supports that convergence of pelvic afferents and pudendal afferents is responsible for bladder excitation evoked by pudendal afferents. Further, abolition of stimulation-evoked bladder contractions following administration of hexamethonium bromide confirmed that contractions were generated by pelvic efferent activation via the pelvic ganglion. These findings indicate that pudendal afferent stimulation evokes bladder contractions through convergence with pelvic afferents to increase pelvic efferent activity.


Conserved loci of leaf and stem rust fungi of wheat share synteny interrupted by lineage-specific influx of repeat elements.
Wheat leaf rust (Puccinia triticina Eriks; Pt) and stem rust fungi (P. graminis f.sp. tritici; Pgt) are significant economic pathogens having similar host ranges and life cycles, but different alternate hosts. The Pt genome, currently estimated at 135 Mb, is significantly larger than Pgt, at 88 Mb, but the reason for the expansion is unknown. Three genomic loci of Pt conserved proteins were characterized to gain insight into gene content, genome complexity and expansion. A bacterial artificial chromosome (BAC) library was made from P. triticina race 1, BBBD and probed with Pt homologs of genes encoding two predicted Pgt secreted effectors and a DNA marker mapping to a region of avirulence. Three BACs, 103 Kb, 112 Kb, and 166 Kb, were sequenced, assembled, and open reading frames were identified. Orthologous genes were identified in Pgt and local conservation of gene order (microsynteny) was observed. Pairwise protein identities ranged from 26 to 99%. One Pt BAC, containing a RAD18 ortholog, shares syntenic regions with two Pgt scaffolds, which could represent both haplotypes of Pgt. Gene sequence is diverged between the species as well as within the two haplotypes. In all three BAC clones, gene order is locally conserved, however, gene shuffling has occurred relative to Pgt. These regions are further diverged by differing insertion loci of LTR-retrotransposon, Gypsy, Copia, Mutator, and Harbinger mobile elements. Uncharacterized Pt open reading frames were also found; these proteins are high in lysine and similar to multiple proteins in Pgt. The three Pt loci are conserved in gene order, with a range of gene sequence divergence. Conservation of predicted haustoria expressed secreted protein genes between Pt and Pgt is extended to the more distant poplar rust, Melampsora larici-populina. The loci also reveal that genome expansion in Pt is in part due to higher occurrence of repeat-elements in this species.


An immunoenzymatic assay for the diagnosis of hepatitis A utilising immunoglobulin Y.
The detection of anti-hepatitis A virus (HAV) antibody levels by diagnostic kits in the convalescent period of disease generally use immunoglobulin G (IgG), which is expensive. An alternative to IgG is immunoglobulin Y (IgY), an immunoglobulin antibody encountered in birds and reptiles. The aim of this study was to develop a competitive immunoenzymatic assay to measure total anti-HAV antibody levels using anti-HAV IgY as the capture and conjugated immunoglobulins. For this purpose, anti-HAV IgY was conjugated to horseradish peroxidase (HRP) and the optimal dilution of HRP-conjugated antibodies was evaluated to establish the competitive immuneenzymatic assay. The results obtained from our "in-house" assay were plotted on a receiver operator curve, which showed a sensitivity of 95% and a specificity of 98.8%, demonstrating that a competitive anti-HAV IgY immunoenzymatic assay developed "in house" could be used as an alternative to commercial assays that utilise IgG.


Phenotypic Heterogeneity and Plasticity of Cancer Cell Migration in a Pancreatic Tumor Three-Dimensional Culture Model.
Invasive cancer cell migration is a key feature of metastatic human pancreatic ductal adenocarcinoma (PDAC), yet the underlying mechanisms remain poorly understood. Here, we investigated modes of cancer cell invasion using two pancreatic cancer cell lines with differential epithelial-mesenchymal status, PANC-1 and BxPC-3, under 3D culture conditions. Multicellular tumor spheroids (TSs) were grown in a collagen matrix co-cultured with pancreatic stellate cells (PSCs) using microchannel chips. PANC-1 cells showed individual migration from TSs via invadopodium formation. BxPC-3 cells showed plasticity between collective and individual migration in either mesenchymal mode, with filopodium-like protrusions, or blebby amoeboid mode. These two cell lines showed significantly different patterns of extracellular matrix (ECM) remodeling, with MMP-dependent degradation in a limited area of ECM around invadopodia for PANC-1 cells, or MMP-independent extensive deformation of ECM for BxPC-3 cells. Cancer cell migration out of the collagen channel significantly increased by PSCs and directional cancer cell migration was mediated by fibronectin deposited by PSCs. Our results highlight the phenotypic heterogeneity and plasticity of PDAC cell migration and ECM remodeling under 3D culture conditions. This 3D co-culture model of pancreatic cancer cells and PSCs offers a useful tool for studying cancer cell migration and ECM remodeling to identify and develop potential molecular targets and anti-cancer agents against human PDAC.


Mitogen-activated protein kinase cascades in Vitis vinifera.
Protein phosphorylation is one of the most important mechanisms to control cellular functions in response to external and endogenous signals. Mitogen-activated protein kinases (MAPK) are universal signaling molecules in eukaryotes that mediate the intracellular transmission of extracellular signals resulting in the induction of appropriate cellular responses. MAPK cascades are composed of four protein kinase modules: MAPKKK kinases (MAPKKKKs), MAPKK kinases (MAPKKKs), MAPK kinases (MAPKKs), and MAPKs. In plants, MAPKs are activated in response to abiotic stresses, wounding, and hormones, and during plant pathogen interactions and cell division. In this report, we performed a complete inventory of MAPK cascades genes in Vitis vinifera, the whole genome of which has been sequenced. By comparison with MAPK, MAPK kinases, MAPK kinase kinases and MAPK kinase kinase kinase kinase members of Arabidopsis thaliana, we revealed the existence of 14 MAPKs, 5 MAPKKs, 62 MAPKKKs, and 7 MAPKKKKs in Vitis vinifera. We identified orthologs of V. vinifera putative MAPKs in different species, and ESTs corresponding to members of MAPK cascades in various tissues. This work represents the first complete inventory of MAPK cascades in V. vinifera and could help elucidate the biological and physiological functions of these proteins in V. vinifera.


Words that describe chronic musculoskeletal pain: implications for assessing pain quality across cultures.
People from different cultures who speak different languages may experience pain differently. This possible variability has important implications for evaluating the validity of pain quality measures that are directly translated into different languages without cultural adaptations. The aim of this study was to evaluate the impact of language and culture on the validity of pain quality measures by comparing the words that individuals with chronic pain from Nepal use to describe their pain with those used by patients from the USA. A total of 101 individuals with chronic musculoskeletal pain in Nepal were asked to describe their pain. The rates of the different pain descriptor domains and phrases used by the Nepali sample were then compared to the published rates of descriptors used by patients from the USA. The content validity of commonly used measures for assessing pain quality was then evaluated. While there was some similarity between patients from Nepal and the USA in how they describe pain, there were also important differences, especially in how pain quality was described. For example, many patients from Nepal used metaphors to describe their pain. Also, the patients from Nepal often used a category of pain descriptor - which describes a physical state - not used by patients from the USA. Only the original McGill Pain Questionnaire was found to have content validity for assessing pain quality in patients from Nepal, although other existing pain quality measures could be adapted to be content valid by adding one or two additional descriptors, depending on the measure in question. The findings indicate that direct translations of measures that are developed using samples of patients from one country or culture are not necessarily content valid for use in other countries or cultures; some adaptations may be required in order for such measures to be most useful in new language and culture.


Ubiquitin-mediated stress response in the spinal cord after transient ischemia.
Vulnerability of motor neurons in the spinal cord against ischemia is considered to play an important role in the development of delayed paraplegia after surgery of the thoracic aorta. However, the reasons for such vulnerability are not fully understood. Recently, the ubiquitin system has been reported to participate in neuronal cell death. In the present study, we investigated the expression of ubiquitin system molecules and discussed the relationship between the vulnerability and the ubiquitin system after transient ischemia in the spinal cord. Fifteen minutes of spinal cord ischemia in rabbits was applied with the use of a balloon catheter. In this model, the spinal motor neuron shows selectively delayed neuronal death, whereas other spinal neurons such as interneurons survive. Immunohistochemical analysis and Western blotting for ubiquitin system molecules, ubiquitin, deubiquitylating enzyme (ubiquitin carboxy-terminal hydrolase 1), and ubiquitin-ligase parkin were examined. In cytoplasm, ubiquitin and ubiquitin carboxy-terminal hydrolase 1 were strongly induced both in interneuron and motor neuron at the early stage of reperfusion, but the sustained expression was observed only in motor neuron. Parkin was induced strongly at 3 hours after the reperfusion, but the immunoreactivity returned to the sham control level at 6 hours in both neurons. In the nuclei, ubiquitin, ubiquitin carboxy-terminal hydrolase 1, and parkin were strongly induced in interneuron, whereas no upregulation of these proteins was observed in motor neuron. These results indicate that the vulnerability of motor neuron of the spinal cord might be partially attributed to the different response in ubiquitin-mediated stress response after transient ischemia.


High-intensity interval training increases SIRT1 activity in human skeletal muscle.
The effects of training on silent mating-type information regulator 2 homolog 1 (SIRT1) activity and protein in relationship to peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and mitochondrial content were determined in human skeletal muscle. Six weeks of high-intensity interval training ( approximately 1 h of 10 x 4 min intervals at 90% peak oxygen consumption separated by 2 min rest, 3 days per week) increased maximal activities of mitochondrial enzymes in skeletal muscle by 28% to 36% (citrate synthase, beta-hydroxyacyl-coenzyme A dehydrogenase, and cytochrome c oxidase subunit IV) and PGC-1alpha protein (16%) when measured 4 days after training. Interestingly, total muscle SIRT1 activity (31%) and activity per SIRT1 protein (58%) increased despite decreased SIRT1 protein (20%). The present data demonstrate that exercise-induced mitochondrial biogenesis is accompanied by elevated SIRT1 activity in human skeletal muscle.


Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.
Small ubiquitin-like modifiers (SUMOs) are post-translational modifications (PTMs) that regulate nuclear cellular processes. Here we used an augmented K0-SUMO proteomics strategy to identify 40,765 SUMO acceptor sites and quantify their fractional contribution for 6,747 human proteins. Structural-predictive analyses revealed that lysines residing in disordered regions are preferentially targeted by SUMO, in notable contrast to other widespread lysine modifications. In our data set, we identified 807 SUMOylated peptides that were co-modified by phosphorylation, along with dozens of SUMOylated peptides that were co-modified by ubiquitylation, acetylation and methylation. Notably, 9% of the identified SUMOylome occurred proximal to phosphorylation, and numerous SUMOylation sites were found to be fully dependent on prior phosphorylation events. SUMO-proximal phosphorylation occurred primarily in a proline-directed manner, and inhibition of cyclin-dependent kinases dynamically affected co-modification. Collectively, we present a comprehensive analysis of the SUMOylated proteome, uncovering the structural preferences for SUMO and providing system-wide evidence for a remarkable degree of cross-talk between SUMOylation and other major PTMs.


Purification and properties of trypsin-like enzyme from the midgut of Morimus funereus (coleoptera, cerambycidae) Larvae.
Trypsin-like enzyme (TLE) from the anterior midgut of Morimus funereus larvae was purified by anion exchange chromatography and gel filtration chromatography and characterized. Specific TLE activity was increased 322-fold by purification of the crude midgut extract. The purified enzyme had a pH optimum of 9.0 (optimum pH range 8.5-9.5) and temperature optimum of 45 degrees C with the K(M) ratio of 0.065 mM for benzoyl-arginine-p-nitroanilide (BApNA). Among a number of inhibitors tested, the most efficient was benzamidine (K(I) value of 0.012 mM, Ic(50) value of 0.204 mM) while inhibition of TLE activity by SBTI, TLCK, and PMSF was partial. Almost all divalent cations tested enhanced the enzyme activity, amongst them Co2+ and Mn2+ stimulated TLE activity for 2.5 times. The purified TLE (after gel-filtration on Superose 12 column) had a molecular mass of 37.5 kDa with an isoelectric point over 9.3. Sodium dodecylsulphate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed one band of 38 kDa, suggesting that the enzyme is a monomer.


Statistical approach to shape from shading: reconstruction of three-dimensional face surfaces from single two-dimensional images.
The human visual system is proficient in perceiving three-dimensional shape from the shading patterns in a two-dimensional image. How it does this is not well understood and continues to be a question of fundamental and practical interest. In this paper we present a new quantitative approach to shape-from-shading that may provide some answers. We suggest that the brain, through evolution or prior experience, has discovered that objects can be classified into lower-dimensional object-classes as to their shape. Extraction of shape from shading is then equivalent to the much simpler problem of parameter estimation in a low-dimensional space. We carry out this proposal for an important class of three-dimensional (3D) objects: human heads. From an ensemble of several hundred laser-scanned 3D heads, we use principal component analysis to derive a low-dimensional parameterization of head shape space. An algorithm for solving shape-from-shading using this representation is presented. It works well even on real images where it is able to recover the 3D surface for a given person, maintaining facial detail and identity, from a single 2D image of his face. This algorithm has applications in face recognition and animation.


Physical activity and quality of life in adult survivors of non-Hodgkin's lymphoma.
To examine the prevalence and correlates of physical activity in adult survivors of aggressive non-Hodgkin's Lymphoma (NHL) and to explore the association between physical activity level and health-related quality of life (HRQOL). Physical activity and HRQOL data from 319 survivors of NHL (mean age, 59.8 years, standard deviation, +/-14.8) who were diagnosed in Los Angeles County approximately 2 to 5 years before the study was analyzed. One quarter of survivors of NHL met public health guidelines of 150 minutes or more of moderate to vigorous exercise per week. More than half (53%) reported some activity but less than 150 minutes per week, whereas 20% reported no physical activity. Females, those with lower perceived health competence, and individuals with more comorbid limitations were at increased risk for inactivity. Individuals who met public health guidelines reported better HRQOL than those who were sedentary. Interestingly, our findings suggest a significant positive association between HRQOL and those who get at least some exercise. The effort to promote physical activity among cancer survivors, who are at risk for poor quality of life as a result of treatment, is of great importance to the health of this growing population. As NHL, similar to other cancers, becomes a disease that people live with as opposed to one that people die as a result of, oncologists and primary care physicians will be increasingly challenged to provide evidence-based guidance for the long-term management of the patient's health. Consideration should be given to how clinicians frame exercise-promoting messages to cancer survivors, especially to those who are sedentary.


Cardiac troponin I associated with the development of unrecognized myocardial infarctions detected with MRI.
Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are sensitive methods to detect subclinical myocardial injury. We sought to investigate the relation between plasma concentrations of cTnI measured with a high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial infarctions (UMIs) detected with LE-MRI. After approval from the ethics committee and written informed consent were obtained, LE-MRI was performed on 248 randomly selected community-living 70-year-old volunteers and hs-cTnI was determined with a highly sensitive premarket assay. Five years later these individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men), who did not have a hospital diagnosis of MI, constitute the present study population. LE-MR images were analyzed by 2 radiologists independently and in a consensus reading, blinded to any information on previous disease or assessments. New or larger UMIs were detected in 37 participants during follow-up. Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within what is considered to be the reference interval, were related to new or larger UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln-transformed cTnI (95% CI, 1.17-3.35; P = 0.010). Plasma concentrations of hs-cTnI at 70 years of age were associated with the volumes of the UMIs detected at 75 years of age (P = 0.028). hs-cTnI in 70-year-old community-living women and men was associated with the development of MRI-detected UMIs within 5 years.


Radiotherapy for breast cancer in countries with limited resources: program implementation and evidence-based recommendations.
Radiotherapy is an essential part of the multimodality treatment of breast cancer. Applying safe and effective treatment requires appropriate facilities, staff, and equipment, as well as support systems, initiation of treatment without undue delay, geographic accessibility, and completion of radiotherapy without undue prolongation of the overall treatment time. Radiotherapy can be delivered with a cobalt-60 unit or a linear accelerator (linac). In early stage breast cancer, radiotherapy is an integral part of breast-conserving treatment. Standard treatment includes irradiation of the entire breast for several weeks, followed by a boost to the tumor bed in women age 50 years or younger or those with close surgical margins. Mastectomy is an appropriate treatment for many patients. Postmastectomy irradiation with proper techniques substantially decreases local recurrences and improves survival in patients with positive axillary lymph nodes. It is also considered for patients with negative nodes if they have multiple adverse features such as a primary tumor larger than 2 cm, unsatisfactory surgical margins, and lymphovascular invasion. Many patients present with locally advanced or inoperable breast cancer. Their initial treatment is by systemic therapy; after responding to systemic therapy, most will require a modified radical mastectomy followed by radiotherapy. For those patients in whom mastectomy is still not possible after initial systemic therapy, breast and regional irradiation is given, followed whenever possible by mastectomy. For patients with distant metastases, irradiation may provide relief of symptoms such as pain, bleeding, ulceration, and lymphedema. A single fraction of irradiation can effectively relieve pain from bone metastases. Radiotherapy is also effective in the palliation of symptoms secondary to metastases in the brain, lungs, and other sites. Radiotherapy is important in the treatment of women with breast cancer of all stages. In developing countries, it is required for almost all women with the disease and should therefore be available.


Relationships of DNA ploidy, S-phase fraction and hormone receptor status to tumor stage in breast cancers detected by population screening. The South-East Sweden Breast Cancer Group.
Cellular DNA content was analyzed by flow cytometry and estrogen and progesterone receptors by an immuno-biochemical method (EIA) in a consecutive series of 807 frozen breast-cancer samples. Before the beginning of the study, a mammography screening program had been introduced in the region where the tumors were diagnosed. Forty percent of the tumors were judged as DNA diploid, of which 86% were ER-positive. The proportion of ER-positive tumors among non-diploids was significantly lower, or 73% (p less than 0.001). S-phase fraction (SPF) was estimated in 691 cases (86%), with an overall mean of 8.4%. DNA ploidy as well as ER and PR status were independently related to SPF. Unlike the results obtained in most older series, the biological variables correlated significantly with tumor staging factors such as lymph-node status and tumor size. Patients with nodal involvement, especially those with 4 positive nodes or more, more often had tumors which were receptor-negative, DNA aneuploid and of high S-phase rate. Large tumor size was significantly related to lower frequencies of receptor positivity and strongly related to DNA aneuploidy and high S-phase fraction. Multiple linear regression analysis showed that these relationships were mainly due to the associations of SPF with the other variables. S-phase fraction was the only independent factor predicting nodal status, while DNA ploidy in addition to SPF was associated with tumor size. In fact, DNA ploidy (p less than 0.001), ER and PR status (p less than 0.001, p = 0.002), nodal status (p = 0.04) and tumor size (p less than 0.001) were all independently related to SPF.