White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging.
Biological causes underpinning the well known gender dimorphisms in human behavior, cognition, and emotion have received increased attention in recent years. The advent of diffusion-weighted magnetic resonance imaging has permitted the investigation of the white matter microstructure in unprecedented detail. Here, we aimed to study the potential influences of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure by investigating transsexuals and healthy controls using diffusion tensor imaging (DTI). Twenty-three female-to-male (FtM) and 21 male-to-female (MtF) transsexuals, as well as 23 female (FC) and 22 male (MC) controls underwent DTI at 3 tesla. Fractional anisotropy, axial, radial, and mean diffusivity were calculated using tract-based spatial statistics (TBSS) and fiber tractography. Results showed widespread significant differences in mean diffusivity between groups in almost all white matter tracts. FCs had highest mean diffusivities, followed by FtM transsexuals with lower values, MtF transsexuals with further reduced values, and MCs with lowest values. Investigating axial and radial diffusivities showed that a transition in axial diffusivity accounted for mean diffusivity results. No significant differences in fractional anisotropy maps were found between groups. Plasma testosterone levels were strongly correlated with mean, axial, and radial diffusivities. However, controlling for individual estradiol, testosterone, or progesterone plasma levels or for subjects' sexual orientation did not change group differences. Our data harmonize with the hypothesis that fiber tract development is influenced by the hormonal environment during late prenatal and early postnatal brain development.


First Report of Phytoplasma Belonging to Apple Proliferation Group in Roses in Poland.
Virus-like diseases of rose plants of uncertain aetiology have been widely distributed throughout the world (4). Symptoms include dieback, rose rosette, witches' broom, and bud proliferation. Research conducted in England (4) and the United States (1) could not reveal the etiology of the diseases. Disease symptoms including stunted growth, leaf and flower malformation, and shoot and flower proliferation were observed in rose plants in Poland (2). In this previous work, we reported cases of phytoplasma closely related to group 16SrI in rose plants with shoot proliferation as determined by nested polymerase chain reaction (PCR) with ribosomal primers R16F1/R0 followed by rA/fA or R16(I)F1/R1. In this study, we examined 48 symptomatic rose plants of 12 cultivars using nested PCR primed by P1/P7 and followed by universal primer pairs R16F2n/R2, fA/rA, or group 16SrI-specific R16(I)F1/R1. To detect potential mixed infection in roses, the group 16SrX-specific primer pairs fAT/rAS, fAT/rPRUS, and fPD/rAT were used for nested PCRs. Samples of rose plants with disease symptoms and nonsymptomatic, samples of Catharanthus roseus, healthy and inoculated by grafting with the reference strain of aster yellows phytoplasma (AY1, group 16SrI-B, kindly supplied by I.-M. Lee, Beltsville, MD) and the reference strain of apple proliferation phytoplasma (AP, group 16SrX-A, kindly supplied by A. Bertaccini, Bologna, Italy), were tested for the presence of phytoplasma rDNA by PCR. Phytoplasma identification was accompanied by digestion with restriction endonucleases, AluI, HhaI, HpaII, MseI, and RsaI, and restriction fragment length polymorphism (RFLP) analysis of a 1.2-kb fragment of rDNA (3). A DNA amplification product was observed in all nested PCRs containing template DNA of samples collected from diseased roses and the reference strains but not from control plants. On the basis of RFLP analysis of PCR products and comparison of the RFLP patterns with those of the reference strains, we demonstrated the presence of aster yellows phytoplasma belonging to phytoplasma group 16SrI-B in roses of 11 cultivars. RFLP profile of samples collected from rose cv. Red Champ was identical to those obtained for reference AP strain (group 16SrX-A). Mixed RFLP profiles were observed in samples collected from rose cv. Memory, which were doubly infected by phytoplasmas belonging to groups 16SrI-B or 16SrX-A. These results were confirmed by PCR with group 16SrX-specific primer pairs. The target DNA was amplified when amplifications were conducted with subgroup 16SrX-A-specific primer pair fAt/rAS, whereas no observable PCR products were obtained with subgroup 16SrX-B- (fAT/rPRUS) or 16SrX-C- (fPD/rAT) specific primer pairs. This report confirms infection of roses by aster yellows phytoplasma belonging to group 16SrI-B, and to our knowledge, records for the first time, infection by phytoplasma of group 16SrX-A. References: (1) A. H. Epstein and J. H. Hill. J. Phytopathol. 143:353, 1995. (2) M. Kami ska et al. J. Phytopathol. 149:3, 2001. (3) I.-B. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1968. (4) B. J. Thomas. Ann. Rep. Glasshouse Crops Res. Inst. 1979:178, 1981.


Anomalous diffusion of heterogeneous populations characterized by normal diffusion at the individual level.
The characterization of the dispersal of populations of non-identical individuals is relevant to most ecological and epidemiological processes. In practice, the movement is quantified by observing relatively few individuals, and averaging to estimate the rate of dispersal of the population as a whole. Here, we show that this can lead to serious errors in the predicted movement of the population if the individuals disperse at different rates. We develop a stochastic model for the diffusion of heterogeneous populations, inspired by the movement of the parasitic nematode Phasmarhabditis hermaphrodita. Direct observations of this nematode in homogeneous and heterogeneous environments reveal a large variation in individual behaviour within the population as reflected initially in the speed of the movement. Further statistical analysis shows that the movement is characterized by temporal correlations and in a heterogeneously structured environment the correlations that occur are of shorter range compared with those in a homogeneous environment. Therefore, by using the first-order correlated random walk techniques, we derive an effective diffusion coefficient for each individual, and show that there is a significant variation in this parameter among the population that follows a gamma distribution. Based on these findings, we build a new dispersal model in which we maintain the classical assumption that individual movement can be described by normal diffusion, but due to the variability in individual dispersal rates, the diffusion coefficient is not constant at the population level and follows a continuous distribution. The conclusions and methodology presented are relevant to any heterogeneous population of individuals with widely different diffusion rates.


Effect of selenium on neurotoxicity in adult male mice exposed to formaldehyde.
Formaldehyde is used in medicine and industry, and it is known to have detrimental effects on various systems including the nervous system, by increasing oxidative stress. However, data are scarce related to substances that can protect against the neurotoxicity induced by formaldehyde. Therefore, this study was designed to assess the protective effects of selenium against the toxic effect of this compound. A total of 48 adult male mice were divided randomly into six groups, i.e., (1) control, (2) treated with formaldehyde, (3) treated with formaldehyde plus 0.1 mg/kg selenium, (4) treated with formaldehyde plus 0.2 mg/kg selenium, (5) treated with formaldehyde plus 0.4 mg/kg selenium, and (6) treated with formaldehyde plus 0.8 mg/kg selenium. At the end of 14 days, the cerebellums were removed for histological evaluation. Morphological changes were examined using Image J software. The data were analyzed using SPSS software version 20.0 and analysis of variance (ANOVA). Formaldehyde caused a reduction in the numbers and sizes of Purkinje cells and granular cells; in addition, the thickness of the granular layer was thinner than that in the control mice (P < 0.05). Treatment with 0.1 mg/kg selenium resulted in an increase in the number of Purkinje cells as well as the area of the gray matter compared to those of the control mice. Formaldehyde-induced neuronal damage was prevented by the administration of 0.1 mg/kg selenium, hence this treatment shows therapeutic potential for the treatment of neurotoxicity.


Global environmental change: local perceptions, understandings, and explanations.
Global environmental change (GEC) is an increasingly discussed phenomenon in the scientific literature as evidence of its presence and impacts continues to grow. Yet, while the documentation of GEC is becoming more readily available, local perceptions of GEC- particularly in small-scale societies-and preferences about how to deal with it, are still largely overlooked. Local knowledge and perceptions of GEC are important in that agents make decisions (including on natural resource management) based on individual perceptions. We carried out a systematic literature review that aims to provide an exhaustive state-of-the-art of the degree to and manner in which the study of local perceptions of change are being addressed in GEC research. We reviewed 126 articles found in peer-reviewed journals (between 1998 and 2014) that address local perceptions of GEC. We used three particular lenses of analysis that are known to influence local perceptions, namely (i) cognition, (ii) culture and knowledge, and (iii) possibilities for adaptation.We present our findings on the geographical distribution of the current research, the most common changes reported, perceived drivers and impacts of change, and local explanations and evaluations of change and impacts. Overall, we found the studies to be geographically biased, lacking methodological reporting, mostly theory based with little primary data, and lacking of indepth analysis of the psychological and ontological influences in perception and implications for adaptation. We provide recommendations for future GEC research and propose the development of a "meta-language" around adaptation, perception, and mediation to encourage a greater appreciation and understanding of the diversity around these phenomena across multiple scales, and improved codesign and facilitation of locally relevant adaptation and mitigation strategies.


Spirituality, distress, depression, anxiety, and quality of life in patients with advanced cancer.
To study the influence of spiritual well being (Sp WB) on symptoms of distress, depression, and other dimensions of quality of life in advanced cancer patients receiving palliative care. The study was cross-sectional in nature. Fifty patients with advanced cancer from a hospice were assessed with the following instruments: the visual analog scale for pain (VAP), M.D. Anderson symptom inventory (MDASI), Hospital Anxiety Depression Scale (HADS), Functional assessment of cancer therapy-Palliative Care (FACT-pal), and Functional assessment of chronic illness therapy-spiritual well-being (FACIT-sp). We studied the correlations between spirituality and other variables on these scales. Depression and anxiety were negatively correlated with spiritual well-being (Sp WB). Sp WB was significantly correlated with fatigue (r = -0.423, P = 0.002), symptom distress (r = -0.717, P < 0.001), memory disturbance (r = -0.520, P < 0.001), loss of appetite (r = -0.399, P = 0.004), drowsiness (r = -0.400, P = 0.004), dry mouth (r = -0.381, P = 0.006), and sadness (r = -0.720, P < 0.001). Sp WB was positively correlated with all the other aspects of QOL measures. Predictors such as palliative care well-being (t = 2.840, P = 0.008), distress (t = -2.582, P = 0.015), sadness (t = -2.765, P = 0.010), mood (t = 2.440, P = 0.021), and enjoyment in life (t = -3.586, P = 0.001) were significantly correlated with Sp WB, after regression analysis. This study suggests that spiritual well being is an important component of the quality of life of advanced cancer patients, and is closely related to the physical and psychological symptoms of distress. It should be addressed appropriately and adequately in palliative care settings.


A distributed model of peritoneal-plasma transport: tissue concentration gradients.
Peritoneal dialysis transport studies were carried out in anesthetized rats. Injections of [14C]EDTA were made by intravenous bolus or intraperitoneal dialysis solution, and blood and peritoneal fluid samples were collected for 1 h. After death and rapid freezing of the animal, transverse sections through the abdominal cavity were cut for quantitative macroautoradiography. The plasma-to-peritoneal transport experiments with a clinical dialysis solution resulted in essentially horizontal concentration profiles versus distance in all tissues except large intestine. Estimates of the extracellular tissue fraction were: small intestine, 0.34; large intestine, 0.28; stomach, 0.30; uterus, 0.66; liver 0.35; diaphragm, 0.16; and anterior abdominal wall, 0.15. Similar experiments with an isotonic salt solution resulted in larger (13-300%) extracellular fractions in all tissues. In contrast, peritoneal-to-plasma transport studies demonstrated decreasing concentration profiles in all visceral tissues, with the first 90% of the gradient contained in the initial 400 micron of tissue from the peritoneum. Parietal tissue gradients were less steep and had higher concentration levels deep within the tissue than visceral tissues. Computer simulations using a distributed model approach compared favorably with the experimental measurements and established the validity of this approach.


Innovative models for in vitro detection of seizure.
Data show that toxicity to the central nervous system (CNS) is the most frequent cause of safety failures during the clinical phase of drug development. CNS endpoints such as seizure pose a safety risk to patients and volunteers and can lead to a loss of competitiveness, delays, and increased costs. Current methods rely on detection in the nonclinical rodent and non-rodent studies required to support clinical trials. There are two main issues with this approach; seizure may be missed in the animal studies and, even if seizure is detected, significant resource has already been invested in the project by this stage. Thus, there is a need to develop improved screening methods that can be used earlier in drug discovery to predict seizure. Advances in stem cell biology coupled with an increased understanding of the role of ion channels in seizure offer an opportunity for a new paradigm in screening. Human derived induced pluripotent stem cells (hiPSCs) representative of almost all cellular subtypes present in the brain can be incorporated into physiologically relevant in vitro models that can be used to determine seizure risk using high-throughput methods. Akin to the success of screening against a panel of ion channels such as hERG to reduce cardiovascular safety liability, the involvement of ion channels in seizure suggests that a similar approach to early seizure detection is valid. Profiling of the ion channels expressed in hiPSC models showing the seizurogenic phenotype coupled with electrophysiological assessment of ion channel function could translate into an ion channel seizure panel for rapid and reliable in vitro detection of seizure. The mechanistic information gathered would support optimal drug design early in development before resources, animals and time have been wasted.


Long-term transgene expression in the RPE after gene transfer with a high-capacity adenoviral vector.
To analyze duration of gene expression in the retinal pigment epithelium (RPE) in immunocompetent animals after gene transfer with a high-capacity adenoviral (HC-Ad) vector. An HC-Ad vector was constructed to express the enhanced green fluorescence protein (EGFP) from the human CMV promoter. This vector (HC-AdFK7) was used to transduce rat RPE cells in cell culture and after subretinal injection in vivo in adult immunocompetent Wistar rats. In cell culture, expression of EGFP was analyzed by fluorescence microscopy. In vivo expression was monitored by scanning laser ophthalmoscopy and stereo fluorescence microscopy. After enucleation of the eyes, immunohistochemical and morphologic analyses by fluorescence light microscopy and electron microscopy were performed. In vitro, RPE cells were efficiently transduced with HC-AdFK7. Expression persisted for the observation time of 8 weeks. In vivo, the RPE was efficiently transduced with low doses of HC-AdFK7. EGFP synthesis was confirmed by antibody staining and found to be stable for the complete study period of 6 months. The neuroretina was well preserved over areas of subretinal vector administration, and significant morphologic changes were not detected. There was no accumulation of inflammatory T cells or macrophages. In contrast to previous results with earlier generation adenoviral vectors, subretinal injection of an HC-Ad vector in immunocompetent rats resulted in long-term transgene expression without evidence of adverse immune reactions or significant toxicity, probably because of the absence of expression of the viral gene from this vector. Thus, HC-Ad vectors are suitable for the treatment of eye disorders that require durable gene expression in the RPE.


Chromosomal breakpoints in primary colon cancer cluster at sites of structural variants in the genome.
Genomic aberrations on chromosome 8 are common in colon cancer, and are associated with lymph node and distant metastases as well as with disease susceptibility. This prompted us to generate a high-resolution map of genomic imbalances of chromosome 8 in 51 primary colon carcinomas using a custom-designed genomic array consisting of a tiling path of BAC clones. This analysis confirmed the dominant role of this chromosome. Unexpectedly, the position of the breakpoints suggested colocalization with structural variants in the human genome. In order to map these sites with increased resolution and to extend the analysis to the entire genome, we analyzed a subset of these tumors (n = 32) by comparative genomic hybridization on a 185K oligonucleotide array platform. Our comprehensive map of the colon cancer genome confirmed recurrent and specific low-level copy number changes of chromosomes 7, 8, 13, 18, and 20, and unveiled additional, novel sites of genomic imbalances including amplification of a histone gene cluster on chromosome 6p21.1-21.33 and deletions on chromosome 4q34-35. The systematic comparison of segments of copy number change with gene expression profiles showed that genomic imbalances directly affect average expression levels. Strikingly, we observed a significant association of chromosomal breakpoints with structural variants in the human genome: 41% of all copy number changes occurred at sites of such copy number variants (P < 2.2e(-16)). Such an association has not been previously described and reveals a yet underappreciated plasticity of the colon cancer genome; it also points to potential mechanisms for the induction of chromosomal breakage in cancer cells.


Mechanical positioning of multiple nuclei in muscle cells.
Many types of large cells have multiple nuclei. In skeletal muscle fibers, the nuclei are distributed along the cell to maximize their internuclear distances. This myonuclear positioning is crucial for cell function. Although microtubules, microtubule associated proteins, and motors have been implicated, mechanisms responsible for myonuclear positioning remain unclear. We used a combination of rough interacting particle and detailed agent-based modeling to examine computationally the hypothesis that a force balance generated by microtubules positions the muscle nuclei. Rather than assuming the nature and identity of the forces, we simulated various types of forces between the pairs of nuclei and between the nuclei and cell boundary to position the myonuclei according to the laws of mechanics. We started with a large number of potential interacting particle models and computationally screened these models for their ability to fit biological data on nuclear positions in hundreds of Drosophila larval muscle cells. This reverse engineering approach resulted in a small number of feasible models, the one with the best fit suggests that the nuclei repel each other and the cell boundary with forces that decrease with distance. The model makes nontrivial predictions about the increased nuclear density near the cell poles, the zigzag patterns of the nuclear positions in wider cells, and about correlations between the cell width and elongated nuclear shapes, all of which we confirm by image analysis of the biological data. We support the predictions of the interacting particle model with simulations of an agent-based mechanical model. Taken together, our data suggest that microtubules growing from nuclear envelopes push on the neighboring nuclei and the cell boundaries, which is sufficient to establish the nearly-uniform nuclear spreading observed in muscle fibers.


The online use of Violence and Journey metaphors by patients with cancer, as compared with health professionals: a mixed methods study.
To compare the frequencies with which patients with cancer and health professionals use Violence and Journey metaphors when writing online; and to investigate the use of these metaphors by patients with cancer, in view of critiques of war-related metaphors for cancer and the adoption of the notion of the 'cancer journey' in UK policy documents. Computer-assisted quantitative and qualitative study of two data sets totalling 753 302 words. A UK-based online forum for patients with cancer (500 134 words) and a UK-based website for health professionals (253 168 words). 56 patients with cancer writing online between 2007 and 2012; and 307 health professionals writing online between 2008 and 2013. Patients with cancer use both Violence metaphors and Journey metaphors approximately 1.5 times per 1000 words to describe their illness experience. In similar online writing, health professionals use each type of metaphor significantly less frequently. Patients' Violence metaphors can express and reinforce negative feelings, but they can also be used in empowering ways. Journey metaphors can express and reinforce positive feelings, but can also be used in disempowering ways. Violence metaphors are not by default negative and Journey metaphors are not by default a positive means of conceptualising cancer. A blanket rejection of Violence metaphors and an uncritical promotion of Journey metaphors would deprive patients of the positive functions of the former and ignore the potential pitfalls of the latter. Instead, greater awareness of the function (empowering or disempowering) of patients' metaphor use can lead to more effective communication about the experience of cancer.


A snapshot of the chalkboard writing experiences of Bachelor of Education students with visual disabilities in South Africa.
South African higher education policy frameworks highlight renewed interest in equity, access and participation imperatives for students with disabilities (SWDs). However, students with visual disabilities continue to face barriers in their teaching practice school placements. This article aims, firstly, to provide early insights into the barriers experienced by students with visual disabilities in their teaching practice school placements in under-resourced schools in KwaZulu-Natal, South Africa. Secondly, it introduces learning communities and a teaching practice pre-placement booklet to enhance equity, access and participation in teaching practice school placements. This study adopted a qualitative methodology using semi-structured interviews to elicit data from two Bachelor of Education students with visual disabilities, who were part of a teaching practice learning community managed by the Disability Unit at the University. Thematic analysis was used, using Tinto's Learning Community Model which generated valuable evidence to argue for institutional commitment to achieve equity, access and participation for students with visual disabilities. Through engagement with a teaching practice learning community and a teaching practice pre-placement booklet, two students with visual disabilities responded to and managed the chalkboard in ways that promoted teaching and learning in the classroom. These retention support trajectories provide evidence to support enhanced equity, access and participation. Given the stigma associated with disability and the need for equity at policy level, higher education institutions should seriously consider systemic mechanisms for access, participation and success outcomes in the teaching practice school placements of students with visual disabilities. Barriers to participation signal the need for accessible teaching and learning strategies for use by students with visual disabilities in their teaching practice school placements. Teaching practice assessors should be alerted to contextual differences in resourced and under-resourced school settings and the diverse ways in which SWDs navigate these differences.


Magnetic resonance imaging in diagnosis of chronic posterolateral rotatory instability of the elbow.
Posterolateral rotatory instability of the elbow can be difficult to diagnose and requires a high degree of clinical suspicion. Cases of chronic posterolateral rotatory instability (symptoms present more than 1 year) may be an even more perplexing subgroup. This is a case report of a patient with a 30-year history of intermittent elbow instability. Clinical examination was equivocal, and magnetic resonance imaging was unable to define any ligamentous injury around the elbow. Examination under anesthesia and surgical findings were consistent with complete disruption of the lateral ulnar collateral ligament. The 12-month follow-up after surgical reconstruction showed complete resolution of symptoms. Posterolateral rotatory instability is a diagnosis largely made by examination under anesthesia. A thorough history and a high clinical suspicion are necessary to support the physician's decision to place the patient under anesthesia. Confirmation of a chronic tear of the lateral ulnar collateral ligament of the elbow with magnetic resonance imaging can be difficult and sometimes misleading.


Adenosine A1 receptor antagonist-induced facilitation of postsynaptic AMPA currents in pyramidal neurons of the rat hippocampal CA2 area.
Adenosine A1 receptors (A1R) are widely expressed in hippocampal pyramidal neurons and their presynaptic terminals. It is well known that endogenous adenosine regulates hippocampal function through the activation of A1R in hippocampal pyramidal neurons and has been reported that blockade of A1R induces stronger potentiation of excitatory synaptic transmission in CA2 pyramidal neurons than in CA1 pyramidal neurons. This strong potentiation of CA2 neurons is thought to be caused by the specific modulation of excitatory synaptic transmission through postsynaptic A1R. However, the direct effects of A1R on postsynaptic AMPA channels remain unknown because of the technical difficulties of patch-clamp recording from mature hippocampal CA2 neurons. We recorded synaptic currents from pyramidal neurons in CA1 and CA2 and analyzed the effects of an A1R antagonist on stimulation-evoked synaptic transmission and local application-induced postsynaptic AMPA currents. The antagonist increased the amplitude of evoked synaptic transmission in neurons in both CA1 and CA2. This facilitation was larger in pyramidal neurons in CA2 than in CA1. The antagonist also increased postsynaptic AMPA currents in neurons in CA2 but not in CA1. This facilitation of CA2 AMPA currents was occluded by the intracellular application of a G-protein blocker. Even with the blockade of postsynaptic G-protein signaling, the A1R antagonist increased evoked synaptic transmission in neurons in CA2. These results suggest that synaptic transmission in pyramidal neurons in CA2 is regulated by both presynaptic and postsynaptic A1R. Moreover, A1R regulate excitatory synaptic transmission in pyramidal neurons in CA2 through the characteristic postsynaptic modulation of AMPA currents.


Communicative interactions improve visual detection of biological motion.
In the context of interacting activities requiring close-body contact such as fighting or dancing, the actions of one agent can be used to predict the actions of the second agent. In the present study, we investigated whether interpersonal predictive coding extends to interactive activities--such as communicative interactions--in which no physical contingency is implied between the movements of the interacting individuals. Participants observed point-light displays of two agents (A and B) performing separate actions. In the communicative condition, the action performed by agent B responded to a communicative gesture performed by agent A. In the individual condition, agent A's communicative action was substituted with a non-communicative action. Using a simultaneous masking detection task, we demonstrate that observing the communicative gesture performed by agent A enhanced visual discrimination of agent B. Our finding complements and extends previous evidence for interpersonal predictive coding, suggesting that the communicative gestures of one agent can serve as a predictor for the expected actions of the respondent, even if no physical contact between agents is implied.


Phase behaviour of active Brownian particles: the role of dimensionality.
Recently, there has been much interest in activity-induced phase separations in concentrated suspensions of "active Brownian particles" (ABPs), self-propelled spherical particles whose direction of motion relaxes through thermal rotational diffusion. To date, almost all these studies have been restricted to 2 dimensions. In this work we study activity-induced phase separation in 3D and compare the results with previous and new 2D simulations. To this end, we performed state-of-the-art Brownian dynamics simulations of up to 40 million ABPs - such very large system sizes are unavoidable to evade finite size effects in 3D. Our results confirm the picture established for 2D systems in which an activity-induced phase separation occurs, with strong analogies to equilibrium gas-liquid spinodal decomposition, in spite of the purely non-equilibrium nature of the driving force behind the phase separation. However, we also find important differences between the 2D and 3D cases. Firstly, the shape and position of the phase boundaries is markedly different for the two cases. Secondly, for the 3D coarsening kinetics we find that the domain size grows in time according to the classical diffusive t(1/3) law, in contrast to the nonstandard subdiffusive exponent observed in 2D.


Survey of family physicians: what is their role in cancer patient care?
In 1993, a survey of randomly-selected family physicians in two regions of Ontario was conducted to assess their views on various aspects of supportive care of patients with cancer. A response rate of 71% was obtained. Results showed that physicians are using preventive and screening techniques in their practices. They are comfortable with most of their roles in supportive cancer care with the exceptions of conveying news of therapy failure and total coordination of care. There is significant dissatisfaction with certain aspects of the timing and content of the consultation letters received from the regional cancer centers. Finally, family physicians expressed the importance of their roles in palliative care.


Transition from high school to work or college: how special education students fare.
Results are reported from the National Longitudinal Transition Study of Special Education Students. Dropout rates were high: 30% of students with disabilities dropped out of high school, and another 8% dropped out before entering high school. The average dropout with disabilities was 18 years old at the time of leaving but had earned less than half the credits needed to graduate. Employment successes were strongly related to taking a concentration (four courses) in vocational education. Youths with learning disabilities or speech impairments were most likely to approach the rate of employment found in the general population. Postsecondary education was low: 37% of high school graduates with disabilities had attended a postsecondary school, compared with 78% of high school graduates generally. Students with hearing or visual impairments were most likely to attend college. Students with disabilities were significantly more likely to be poor than were youths in the general population, and poverty tended to exacerbate the impact of having a disability. Impoverished students with disabilities were less likely than wealthier students with disabilities to be enrolled in those postsecondary education and training programs that could enable them to break out of poverty. When employed, the poorer students with disabilities earned significantly less per year than did those from wealthier families. Placement in regular education (rather than special education) was associated both with better and worse postschool outcomes. Students with sensory or motor disabilities appeared to benefit from regular education placement. However, for many students, more time in regular education was associated with a higher likelihood of course failure, which was a strong predictor of dropping out of school.


Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study.
We conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat. Common genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios. We analysed the effect of these instrumental variables in a colorectal cancer genome-wide association study comprising 31,197 cases and 61,770 controls of European ancestry by applying two-sample and multivariable MR study designs. We found decreased colorectal cancer risk for genetically represented measures of MVPA and AMPA that were additional to effects mediated through genetic measures of obesity. Odds ratio and 95% confidence interval (CI) per standard deviation increase in MVPA and AMPA was 0.56 (0.31, 1.01) and 0.60 (0.41, 0.88), respectively. No association has been found between sedentary time and colorectal cancer risk. The proportion of effect mediated through BMI was 2% (95% CI: 0, 14) and 32% (95% CI: 12, 46) for MVPA and AMPA, respectively. These findings provide strong evidence to reinforce public health measures on preventing colorectal cancer that promote PA at a population level regardless of body fatness.


Depressive symptoms across the menopause transition: findings from a large population-based cohort study.
The aim of the study was to describe the trajectories of depressive symptoms in a large population-based cohort of midaged women, and to examine the associations of current and changing reproductive stage with depressive symptoms over time. Prospective, population-based cohort study of 13,715 women aged 45 to 50 years followed up for over 15 years (Australian Longitudinal Study on Women's Health). Nearly 6,000 women provided complete data for this study. Menopause status was determined from questionnaires about hysterectomy, oophorectomy, hormone therapy, and menstrual patterns. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression scale (CESD-10). Latent class analysis indicated four distinct profiles of CESD-10 scores over 15 years: stable low (80.0%), increasing (9.0%), decreasing (8.5%), and stable high (2.5%). Those with "increasing" depressive symptoms were more likely to have had bilateral salpingo-oophorectomy or be perimenopausal at baseline compared with women in the "stable low" group. Depressive symptoms were higher in perimenopausal women, (higher CESD-10 score of 0.19, 95% CI 0.02, 0.31), after hysterectomy alone (0.53, 95% CI 0.31, 0.74), bilateral salpingo-oophorectomy with/without hysterectomy (0.85, 95% CI 0.58, 1.12), hormone therapy users (0.19, 95% CI 0.01, 0.36), and after starting or stopping hormone therapy compared with postmenopausal women (adjusted for sociodemographic factors, vasomotor symptoms, health behaviors, and history of depression diagnosis or treatment). Depressive symptoms follow distinct trajectories across the menopause transition. Most women have stable symptoms, but around 9% have increasing symptoms and a similar proportion (8.5%) decreasing symptoms. Increasing depressive symptoms were independent of vasomotor symptoms but were associated with oophorectomy and stopping or starting hormone therapy. A large number of women were excluded due to missing data, and thus the results should be interpreted with caution.


Mixtures of Shifted AsymmetricLaplace Distributions.
A mixture of shifted asymmetric Laplace distributions is introduced and used for clustering and classification. A variant of the EM algorithm is developed for parameter estimation by exploiting the relationship with the generalized inverse Gaussian distribution. This approach is mathematically elegant and relatively computationally straightforward. Our novel mixture modelling approach is demonstrated on both simulated and real data to illustrate clustering and classification applications. In these analyses, our mixture of shifted asymmetric Laplace distributions performs favourably when compared to the popular Gaussian approach. This work, which marks an important step in the non-Gaussian model-based clustering and classification direction, concludes with discussion as well as suggestions for future work.


Donation after brain circulation determination of death.
The fundamental determinant of death in donation after circulatory determination of death is the cessation of brain circulation and function. We therefore propose the term donation after brain circulation determination of death [DBCDD]. In DBCDD, death is determined when the cessation of circulatory function is permanent but before it is irreversible, consistent with medical standards of death determination outside the context of organ donation. Safeguards to prevent error include that: 1] the possibility of auto-resuscitation has elapsed; 2] no brain circulation may resume after the determination of death; 3] complete circulatory cessation is verified; and 4] the cessation of brain function is permanent and complete. Death should be determined by the confirmation of the cessation of systemic circulation; the use of brain death tests is invalid and unnecessary. Because this concept differs from current standards, consensus should be sought among stakeholders. The patient or surrogate should provide informed consent for organ donation by understanding the basis of the declaration of death. In cases of circulatory cessation, such as occurs in DBCDD, death can be defined as the permanent cessation of brain functions, determined by the permanent cessation of brain circulation.


Paracoccidioidomycosis in Brazilian Patients With and Without Human Immunodeficiency Virus Infection.
Paracoccidioidomycosis (PCM) is endemic to Latin America, where 10 million people may be infected with Paracoccidioides brasiliensis/Paracoccidioides lutzii and 1,600,000 individuals live with human immunodeficiency virus (HIV) infection. An epidemiological overlapping of these infections occurred early in acquired immunodeficiency syndrome era with nearly 180 published cases. This study presents epidemiological, clinical, and outcome profiles for 31 PCM patients with HIV infection diagnosed in a teaching hospital in Brazil, and includes an update of previously reported cases. Medical records were reviewed and data compared with 64 PCM patients without HIV infection. Of the 31 PCM patients with HIV infection, 23 (74.1%) were male, with a median age of 36.7 years, whereas of the 64 PCM, 45 (70.3%) were male, with a median age of 35.1 years. Both groups presented similar proportions for smoking and alcoholism. PCM patients with HIV infection presented more fever, weight loss, and the acute clinical form than the PCM patients who had more mucosal and respiratory involvement characterizing the chronic form. Most PCM patients with HIV infection exhibited overlapping symptoms from both clinical forms with median symptom duration of 4.5 months compared with 8.3 months for the PCM control. Patients received sulfonamides and/or itraconazole for a median of 15.7 and 16.7 months for PCM/HIV-infected and PCM, respectively. Relapses occurred more in PCM (12 [30%]) than PCM/HIV-infected (4 [14.8%]) patients, whose mortality rate was higher (10 [32.8%]) than PCM patients (8 [20%]). The cases of PCM/HIV infection confirm that HIV can interact with some endemic diseases without increasing their frequency, while changing their natural history, clinical presentation, and outcome. The data presented here are in agreement with those observed in other studies.


Farnesyl thiosalicylic acid inhibits the growth of melanoma cells through a combination of cytostatic and pro-apoptotic effects.
Novel classes of drug that interfere with the signalling of the small G-protein Ras, the so-called Ras antagonists, are showing much promise as novel anti-cancer agents. In this study, we demonstrate that the novel Ras antagonist farnesylthiosalicylic acid (FTS) inhibits the growth of Colo 853 melanoma cells through a combination of cytostatic and pro-apoptotic effects. Furthermore, these phenomena are seen under conditions of cell attachment and in the presence of serum. Treatment of Colo 853 cells with FTS led to time-dependent inhibition of constitutive Akt, retinoblastoma protein (pRB) and ERK activity, with a concurrent loss of Akt expression. Inhibition of Akt and ERK activity induces apoptosis in other human cancer cell lines. Here it is demonstrated that inhibition of Akt, or ERK and Akt in combination, leads to cell cycle arrest but not apoptosis in melanoma cells. FTS treatment was also found to upregulate activity of the stress-activated p38 MAP kinase. Inhibition of p38 MAP kinase, using the selective inhibitor SB 203580, followed by FTS treatment, significantly increased the proportion of apoptotic cells after 72 hr, possibly suggesting a modulatory role for p38 MAP kinase in FTS-induced melanoma cell apoptosis.


Mendel's stem length gene (Le) encodes a gibberellin 3 beta-hydroxylase.
We describe the isolation of the Le gene of pea, which controls internode elongation and originally was described by Mendel. Heterologous screening of a pea cDNA library yielded a partial clone that was 61% identical to coding regions of the putative Arabidopsis gibberellin 3 beta-hydroxylase gene, GA4. DNA gel blot analysis with this cDNA revealed a HindIII restriction fragment length polymorphism between pea isolines differing at Mendel's Le locus. Genomic clones of the GA4-related gene were isolated from the Le and le isolines. Polymerase chain reaction combined with restriction fragment length polymorphism analysis were used to show that the gene mapped to the Le locus. A cDNA containing a complete open reading frame of the pea GA4-related gene was amplified by polymerase chain reaction from each isoline. Recombinant expression in Escherichia coli demonstrated that the product of the Le cDNA was a gibberellin 3 beta-hydroxylase that is able to convert GA20 to the bioactive GA1. Substantially reduced levels of gibberellin 3 beta-hydroxylase activity were measured, after expression of the le cDNA, by using identical methods. This reduced activity was associated with an alanine-to-threonine substitution in the predicted amino acid sequence of the enzyme near its proposed active site.


Comparison of efficiency and specificity of CRISPR-associated (Cas) nucleases in plants: An expanded toolkit for precision genome engineering.
Molecular tools adapted from bacterial CRISPR (Clustered Regulatory Interspaced Short Palindromic Repeats) systems for adaptive immunity have become widely used for plant genome engineering, both to investigate gene functions and to engineer desirable traits. A number of different Cas (CRISPR-associated) nucleases are now used but, as most studies performed to date have engineered different targets using a variety of plant species and molecular tools, it has been difficult to draw conclusions about the comparative performance of different nucleases. Due to the time and effort required to regenerate engineered plants, efficiency is critical. In addition, there have been several reports of mutations at sequences with less than perfect identity to the target. While in some plant species it is possible to remove these so-called 'off-targets' by backcrossing to a parental line, the specificity of genome engineering tools is important when targeting specific members of closely-related gene families, especially when recent paralogues are co-located in the genome and unlikely to segregate. Specificity is also important for species that take years to reach sexual maturity or that are clonally propagated. Here, we directly compare the efficiency and specificity of Cas nucleases from different bacterial species together with engineered variants of Cas9. We find that the nucleotide content of the target correlates with efficiency and that Cas9 from Staphylococcus aureus (SaCas9) is comparatively most efficient at inducing mutations. We also demonstrate that 'high-fidelity' variants of Cas9 can reduce off-target mutations in plants. We present these molecular tools as standardised DNA parts to facilitate their re-use.


Study of HfO2/SiO2 dichroic laser mirrors with refractive index inhomogeneity.
HfO2/SiO2 dichroic mirrors, having high reflectance at 1064 nm and high transmittance at 532 nm, play an important role in high-power laser systems. However, the half-wave hole effect, caused mainly by the refractive index inhomogeneity of hafnia, affects the spectra and application of these mirrors. Two approaches to eliminate the half-wave hole effect have been proposed. Both approaches attempt to shift the location of the half-wave hole in comparison with the original wavelength. One approach broadens the reflectance band of the first harmonic wavelength and simultaneously adjusts the central reflectance band to a longer wavelength, whereas the other approach combines the two stacks to adjust the location of the half-wave hole far away from the wavelength of interest. Two kinds of dichroic mirrors have been successfully fabricated; moreover, it was found that the method of a two-stack combination, 0.9(HL)8 and 1.1(HL)8, provides designs that can be fabricated more easily and with better quality spectral characteristics.


Impact of between-hospital volume and within-hospital volume on mortality and readmission rates for trauma patients in California.
Previous research assessing the impact of between-hospital trauma volume (high volume centers vs. low volume centers) and outcomes has been inconsistent. Furthermore, previous research has not considered temporal variations in within-hospital volume (a center having higher than average volume vs. lower than average volume) as a covariate. The objective of this study was to determine the relationship of between-hospital and within-hospital trauma volume and two measures of hospital quality of care. Multivariable, hierarchical, mixed effects, logistic regression analyses of a population-based nonconcurrent cohort from 1995 to 1999. Thirty-nine nonfederal California hospitals included in the California Patient Discharge Data Set designated by local Emergency Medical Services authorities as adult trauma centers. All nonelderly adult trauma patients, 16-64 yrs (n = 54,352), and elderly adult trauma patients, >65 yrs (n = 47,656), admitted with an Injury Severity Score >9. None. Severity adjusted in-hospital mortality rate and 30-day trauma-related readmissions were analyzed. Among nonelderly adult patients, higher annual between-hospital trauma volume was not associated with mortality rate (odds ratio, 1.02 for each 100 admissions; 95% confidence interval, 0.99, 1.06) but was associated with higher risk of readmission (odds ratio, 1.19 for each 100 admissions; 95% confidence interval, 1.13, 1.26). Among elderly adult patients, higher annual between-hospital trauma volume was associated with lower mortality (odds ratio, 0.79 for each 100 admissions; 95% confidence interval, 0.71, 0.87) but was not associated with risk of readmission (odds ratio, 0.96 for each 100 admissions; 95% confidence interval, 0.90, 1.04). Higher than average monthly within-hospital trauma volume was associated with higher odds of readmission (odds ratio, 1.11 for a volume deviation of ten patients per month; 95% confidence interval, 1.01, 1.21) among elderly adult patients. The findings of this study in the context of previous research suggest that relationships between trauma volume and outcomes exist but depend on which patient populations are studied and how the data are analyzed. Furthermore, trauma centers may be subject to the detrimental effects of high temporal volume overextending existing services and capacity. Since this study found that both between-hospital volume and within-hospital volume measures are associated with outcomes, we recommend that both measures be included in future volume-outcome investigations.


Femtoliter Volumetric Pipette and Flask Utilizing Nanofluidics.
Microfluidics has achieved integration of analytical processes in microspaces and realized miniaturized analyses in fields such as chemistry and biology. We have proposed a general concept of integration and extended this concept to the 10-1000 nm scale exploring ultimate analytical performances (e.g. immunoassay of a single-protein molecule). However, a sampling method is still challenging for nanofluidics despite its importance in analytical chemistry. In this study, we developed a femtoliter (fL) sampling method for volume measurement and sample transport. Traditionally, sampling has been performed using a volumetric pipette and flask. In this research, a nanofluidic device consisting of a femtoliter volumetric pipette and flask was fabricated on glass substrates. Since gravity, which is exploited in bulk fluidic operations, becomes less dominant than surface effects on the nanometer scale, fluidic operation of the femtoliter sampling was designed utilizing surface tension and air pressure control. The working principle of an 11 fL volumetric pipette and a 50 fL flask, which were connected by a nanochannel, was verified. It was found that evaporation of the sample solution by air flow was a significant source of error because of the ultra-small volumes being processed. Thus, the evaporation issue was solved by suppressing the air flow. As a result, the volumetric measurement error was decreased to ±0.06 fL (CV 0.6%), which is sufficiently low for use in nanofluidic analytical applications. This study will present a fundamental technology for the development of novel analytical methods for femtoliter volume samples such as single molecule analyses.


Adenosine receptor A3 is a critical mediator in LPS-induced pulmonary inflammation.
Adenosine receptor A(3) (A(3)) regulates directed movement of polymorphonuclear cells (PMNs) to sites of inflammation and has been implicated as a relevant mediator in models of inflammatory diseases. Here, we sought to characterize the role of A(3) in a murine model of lung inflammation. Initial studies revealed that pulmonary A(3) transcript levels were elevated following LPS exposure in vivo. In addition, inhalation of LPS increased the accumulation of PMNs in wild-type and A(3)(-/-) mice in all lung compartments. Pretreatment with the specific A(3)-agonist Cl-IB-MECA significantly decreased migration of PMNs into lung interstitium and alveolar air space of wild-type mice but not of A(3)(-/-) mice. Lower PMN counts were associated with reduced levels of TNF-α and IL-6 in the alveolar space of wild-type mice that received Cl-IB-MECA. In addition, Cl-IB-MECA attenuated LPS-induced microvascular permeability in wild-type mice as assessed by the extravasation of Evans blue. In pulmonary microvascular endothelial cells, Cl-IB-MECA reduced LPS-induced cytoskeletal remodeling and cell retraction, consistent with a specific role of A(3) for maintaining endothelial integrity. Migratory activity of human PMNs across an endothelial or epithelial monolayer was reduced when A(3) was activated on PMNs. Studies in chimeric mice, however, revealed that Cl-IB-MECA required A(3) on both hematopoietic and nonhematopoietic cells to reduce transmigration in vivo. Together, our results shed new light on the role of A(3) in LPS-induced PMN trafficking in the lung and suggest pharmacological modulation of A(3)-dependent pathways as a promising approach in lung inflammation.


Effects of radon inhalation on biological function--lipid peroxide level, superoxide dismutase activity, and membrane fluidity.
We administered radon (Rn) to rabbits by inhalation and examined changes in the lipid peroxide (TBARS) level, superoxide dismutase (SOD) activity, and membrane fluidity in various organs to clarify the therapeutic effects of Rn. The lipid peroxide level of the brain was significantly decreased immediately after Rn inhalation for 90 min in both the low concentration group (about 7-10 kBq/liter) and the high concentration group (about 14-18 kBq/liter) as compared with that in the control group. It further decreased in the low concentration group but slightly recovered in the high concentration group 2 h after inhalation. The lipid peroxide level of the lung showed no change immediately after inhalation but decreased significantly in both groups 2 h after inhalation. With regard to SOD activity in the brain and lung, only that in the brain showed significant increase in the high concentration group immediately after inhalation; no other change was observed. Membrane fluidity, especially the fluidity of membrane protein, was significantly increased in the brains of both groups immediately after inhalation, and that 2 h after inhalation in the lung was significantly increased in both groups. These findings suggest that the inhalation of Rn at Rn springs contributes to the prevention of brain disorders related to peroxidation reactions by promoting these physiologic changes.


Rationale and design of the SYNTAX II trial evaluating the short to long-term outcomes of state-of-the-art percutaneous coronary revascularisation in patients with de novo three-vessel disease.
The applicability of the results of the SYNTAX trial comparing percutaneous coronary intervention (PCI) using first-generation drug-eluting stents (DES) with coronary artery bypass graft (CABG) surgery for the treatment of patients with complex coronary artery disease (CAD) has been challenged by recent major technical and procedural developments in coronary revascularisation. Functional assessment of coronary lesions has contributed to marked improvements in both safety and efficacy of DES implantation. In addition, the recent development of the SYNTAX score II, a clinical tool based on anatomical and clinical factors, allows individualised objective decision making regarding the optimal revascularisation modality in patients with complex CAD. The ongoing SYNTAX II trial is currently evaluating the effectiveness of the clinical and technological advances in the treatment of patients with complex (de novo three-vessel) CAD. The SYNTAX II trial is a multicentre, all-comers, open-label, single-arm trial aiming to recruit 450 patients with de novo three-vessel CAD in approximately 25 European interventional cardiology centres. All patients will be selected and treated following the SYNTAX II strategy, which includes: a) establishing the appropriateness of revascularisation utilising the SYNTAX score II as a clinical tool to allow objective decision making by the Heart Team, b) ischaemia-driven revascularisation based on functional intracoronary assessment, c) implantation of the new-generation everolimus-eluting platinum chromium coronary stent with thin struts and abluminal bioabsorbable polymer coating to promote rapid vessel healing, d) intravascular ultrasound-guided DES implantation, and e) treatment at centres with expertise in CTO recanalisation. The primary endpoint is a composite of the major adverse cardiac and cerebral events (MACCE) rate at one-year follow-up compared to the historical PCI arm of the SYNTAX trial. An exploratory endpoint will be MACCE at five-year follow-up compared to the historical surgical arm of the SYNTAX trial. The SYNTAX II trial will provide valuable information on outcomes of state-of-the-art PCI for the contemporary management of complex (de novo three-vessel) CAD. SYNTAX II will be of critical value in the design of future trials in this arena.


Differential Susceptibility of Xylella fastidiosa Strains to Synthetic Bactericidal Peptides.
The kinetics of cell inactivation and the susceptibility of Xylella fastidiosa subspecies fastidiosa, multiplex, and pauca to synthetic antimicrobial peptides from two libraries (CECMEL11 and CYCLO10) were studied. The bactericidal effect was dependent on the relative concentrations of peptide and bacterial cells, and was influenced by the diluent, either buffer or sap. The most bactericidal and lytic peptide was BP178, an enlarged derivative of the amphipathic cationic linear undecapeptide BP100. The maximum reduction in survivors after BP178 treatment occurred within the first 10 to 20 min of contact and at micromolar concentrations (<10 μM), resulting in pore formation in cell membranes, abundant production of outer membrane vesicles, and lysis. A threshold ratio of 109 molecules of peptide per bacterial cell was estimated to be necessary to initiate cell inactivation. There was a differential susceptibility to BP178 among strains, with DD1 being the most resistant and CFBP 8173 the most susceptible. Moreover, strains showed a proportion of cells under the viable but nonculturable state, which was highly variable among strains. These findings may have implications for managing the diseases caused by X. fastidiosa.


Can novice drivers be trained to scan for information that will reduce their likelihood of a crash?
Sixteen year old drivers are involved in 10.3 fatal crashes per 100 million vehicle miles, a rate almost double that of 18 year olds and almost eight times that of 45-64 year olds, who are the safest group of drivers. Crash rates are particularly higher during the first month of licensure and decline rapidly for about six months and 1000 miles and then much more slowly for at least two years, consistent with a typical learning curve. Research indicates that drivers who have their learner's permit or are just newly licensed have particular difficulties identifying areas of a scenario from which hidden risks could emerge. Standard driver education programs do not appear to address these difficulties adequately. This suggests that some alternative form of driver training could reduce the crashes, either in the classroom or on the road. A PC based program designed to teach drivers to recognize risks early on is shown to improve their awareness of hazards, both on an advanced driving simulator and on the road.


Feasibility report of image guided stereotactic body radiotherapy (IG-SBRT) with tomotherapy for early stage medically inoperable lung cancer using extreme hypofractionation.
We report on the technical feasibility, dosimetric aspects, and daily image-guidance capability with megavoltage CT (MVCT) of stereotactic body radiotherapy (SBRT) using helical tomotherapy for medically inoperable T1/2 N0 M0 non-small cell lung cancer. Nine patients underwent treatment planning with 4D-CT in a double vacuum based immobilization system to minimize tumor motion and to define a lesion-specific 4D-motion envelope. Patients received 60 Gy in 5 fractions within 10 days to a PTV defined by a motion envelope plus a 6 mm expansion for microscopic extension and setup error using tomotherapy, with daily pretreatment MVCT image guidance. The primary endpoint was technical feasibility. Secondary endpoints were defining the acute and sub-acute toxicities and tumor response. Forty three of 45 fractions were successfully delivered, with an average delivery time of 22 minutes. MVCT provided excellent tumor visualization for daily image guidance. No significant tumor regression was observed on MVCT in any patient during therapy. Median mean normalized total doses were: tumor 117 Gy10; residual lung 9 Gy3. Maximum fraction-size equivalent dose values were: esophagus 5 Gy39; cord 7 Gy36. No patient experienced > or = grade 2 pulmonary toxicity. 3 complete, 4 partial and 2 stable responses were observed, with <3 months median follow-up. The mean tumor regression is 72%. SBRT using tomotherapy proved to be feasible, safe and free of major technical limitations or acute toxicities. Daily pretreatment MVCT imaging allows for precise daily tumor targeting with the patient in the actual treatment position, and therefore provides for precise image guidance.


Genetic differentiation of the marbled white butterfly, Melanargia galathea, accounts for glacial distribution patterns and postglacial range expansion in southeastern Europe.
Isolation of Mediterranean species in the southern European peninsulas during the cold glacial phases often resulted in differentiation of several genetic lineages confined to the respective peninsulas. However, whilst there is good genetic evidence for multiple refugia in Iberia, there are only limited data available for the Balkans. Therefore, we wish to examine the hypothesis of a strong genetic structuring within southeastern Europe for the existence of multiple Balkan differentiation centres and/or several leading edges. As a model we use the marbled white butterfly, Melanargia galathea. We studied 18 allozyme loci of 564 individuals from 16 populations distributed over a large part of southeastern Europe. The single populations showed moderately high genetic diversity and no northward decline of genetic diversity was detected. The overall genetic differentiation between populations was considerable (F(ST) 7.0%). Cluster analysis discriminated three genetic groups: (i) a western flank in the former Yugoslavia, parts of eastern Austria and Hungary; (ii) an eastern flank with populations from Bulgaria and Romania (south of the southern Carpathians and eastern Carpathians); and (iii) the eastern Carpathian Basin. Hierarchical variance analysis distributed 53% of the variance among populations between these three groups. One sample from the Greek-Bulgarian border clustered within the eastern flank, but showed some tendency towards the eastern Carpathian Basin populations. Two populations from Carinthia clustered together with the eastern Carpathian Basin ones and a population from Styria showed an intermediate genetic composition between the three groups. Most probably, the eastern and the western flank groups are due to postglacial range expansion from the northeastern and the northwestern edges of the glacial differentiation centre (so-called leading edges). The eastern Carpathian Basin group may have resulted from postglacial expansion from northern Greece through valley systems of the central Balkan peninsula, maybe even expanding westwards north of the Balkan mountains reaching some parts of eastern Austria (e.g. Carinthia). Therefore, the Balkanic refugium of M. galathea may or may not have been continuous along the coastal areas of the Mediterranean, but must have been strongly genetically structured.


Authentic early experience in Medical Education: a socio-cultural analysis identifying important variables in learning interactions within workplaces.
This paper addresses the question 'what are the variables influencing social interactions and learning during Authentic Early Experience (AEE)?' AEE is a complex educational intervention for new medical students. Following critique of the existing literature, multiple qualitative methods were used to create a study framework conceptually orientated to a socio-cultural perspective. Study participants were recruited from three groups at one UK medical school: students, workplace supervisors, and medical school faculty. A series of intersecting spectra identified in the data describe dyadic variables that make explicit the parameters within which social interactions are conducted in this setting. Four of the spectra describe social processes related to being in workplaces and developing the ability to manage interactions during authentic early experiences. These are: (1) legitimacy expressed through invited participation or exclusion; (2) finding a role-a spectrum from student identity to doctor mindset; (3) personal perspectives and discomfort in transition from lay to medical; and, (4) taking responsibility for 'risk'-moving from aversion to management through graded progression of responsibility. Four further spectra describe educational consequences of social interactions. These spectra identify how the reality of learning is shaped through social interactions and are (1) generic-specific objectives, (2) parallel-integrated-learning, (3) context specific-transferable learning and (4) performing or simulating-reality. Attention to these variables is important if educators are to maximise constructive learning from AEE. Application of each of the spectra could assist workplace supervisors to maximise the positive learning potential of specific workplaces.


Expanding the Validity of the Level of Personality Functioning Scale Observer Report and Self-Report Versions Across Psychodynamic and Interpersonal Paradigms.
The Level of Personality Functioning Scale (LPFS) operationalizes Criterion A of the DSM-5 alternative model for personality disorders. Yet, research on this measure has been slow to accumulate and questions remain regarding its reliability and validity. This study examined the LPFS observer-rated (OR) and self-report (SRA) versions of Criterion A in a sample of 240 students who provided psychological life history data and a variety of self-report measures. The results suggested the LPFS OR could be reliably coded, and the LPFS OR and LPFS SRA were significantly associated with outcome variables across psychodynamic and interpersonal paradigms. We discuss the implications of assessing personality dysfunction using the LPFS and the importance of expanding the research base for the AMPD model.


Influences of surface coating, UV irradiation and magnetic field on the algae removal using magnetite nanoparticles.
Magnetophoretic separation is a promising and sustainable technology for rapid algal separation or removal from water. This work demonstrated the application of magnetic magnetite nanoparticles (MNPs) coated with a cationic polymer, polyethylenimine (PEI), toward the separation of Scenedesmus dimorphus from the medium broth. The influences of surface coating, UV irradiation, and magnetic field on the magnetophoretic separation were systematically examined. After PEI coating, zeta potential of MNPs shifted from −7.9 ± 2.0 to +39.0 ± 3.1 mV at a pH of 7.0, which improved MNPs-algae interaction and helped reduce the dose demand of MNPs (e.g., from 0.2 to 0.1 g·g(–1) while the harvesting efficiency (HE) of over 80% remained unchanged). The extended Derjaguin–Landau–Verwey–Overbeek theory predicted a strong attractive force between PEI-coated MNPs and algae, which supported the improved algal harvesting. Moreover, the HE was greater under the UV365 irradiation than that under the UV254, and increased with the irradiation intensity. Continuous application of the external magnetic field at high strength remarkably improved the algal harvesting. Finally, the reuse of MNPs for multiple cycles of algal harvesting was studied, which aimed at increasing the sustainability and lowering the cost.


Brain regions and molecular pathways responding to food reward type and value in honey bees.
The ability of honey bees to evaluate differences in food type and value is crucial for colony success, but these assessments are made by individuals who bring food to the hive, eating little, if any, of it themselves. We tested the hypothesis that responses to food type (pollen or nectar) and value involve different subsets of brain regions, and genes responsive to food. mRNA in situ hybridization of c-jun revealed that brain regions responsive to differences in food type were mostly different from regions responsive to differences in food value, except those dorsal and lateral to the mushroom body calyces, which responded to all three. Transcriptomic profiles of the mushroom bodies generated by RNA sequencing gave the following results: (1) responses to differences in food type or value included a subset of molecular pathways involved in the response to food reward; (2) genes responsive to food reward, food type and food value were enriched for (the Gene Ontology categories) mitochondrial and endoplasmic reticulum activity; (3) genes responsive to only food and food type were enriched for regulation of transcription and translation; and (4) genes responsive to only food and food value were enriched for regulation of neuronal signaling. These results reveal how activities necessary for colony survival are channeled through the reward system of individual honey bees.


Highly cited works in neurosurgery. Part II: the citation classics.
The term "citation classic" has been used in reference to an article that has been cited more than 400 times. The purpose of this study is to identify such articles that pertain to clinical neurosurgery. A list of search phrases relating to neurosurgery was compiled. A topic search was performed using the Institute for Scientific Information Web of Science for phrases. Articles with more than 400 citations were identified, and nonclinical articles were omitted. The journals, year of publication, topics, and study types were analyzed. There were 106 articles with more than 400 citations relating to clinical neurosurgery. These articles appeared in 28 different journals, with more than half appearing in the Journal of Neurosurgery or the New England Journal of Medicine. Fifty-three articles were published since 1990. There were 38 articles on cerebrovascular disease, 21 on stereotactic and functional neurosurgery, 21 on neurooncology, 19 on trauma, 4 on nontraumatic spine, 2 on CSF pathologies, and 1 on infection. There were 29 randomized trials, of which 86% appeared in the New England Journal of Medicine, Lancet, or the Journal of the American Medical Association, and half concerned the prevention or treatment of stroke. In addition, there were 16 prospective studies, 15 classification or grading systems, and 7 reviews. The remaining 39 articles were case series, case reports, or technical notes. More than half of the citation classics identified in this study have been published in the past 20 years. Case series, classifications, and reviews appeared more frequently in neurosurgical journals, while randomized controlled trials tended to be published in general medical journals.


Lesionectomy versus electrophysiologically guided resection for temporal lobe tumors manifesting with complex partial seizures.
Complex partial seizures associated with tumors and other mass lesions are readily diagnosed by modern imaging techniques but their optimum surgical treatment remains unresolved. Lesionectomy has been reported to produce seizure outcomes equal to outcomes after resection that ablates the epileptogenic cortex with the lesion. However, some evidence suggests that when the lesion is in the temporal lobe, simple excision of the tumor or lesion more often fails to control seizures. After retrospectively reviewing the records of 30 patients with complex partial seizures and temporal lobe tumors who underwent surgical treatment at the University of Cincinnati hospitals (1985-1992), the authors divided them into two groups: Group A (16 patients) underwent lesionectomy only and Group B (14 patients) received surgical treatment for seizures with electroencephalographic delineation of the epileptogenic zone and resection of the lesion. Seizure control was best achieved in Group B patients with 13 (92.8%) seizure free at follow up (mean 52 months). Only three (18.8%) of the Group A patients became seizure free after lesionectomy at follow up (mean 33 months). In eight Group A patients, who underwent temporal lobectomy as a second procedure after lesionectomy failed to control seizures, five (62.5%) became seizure free. Group B patients had a longer duration of seizures and were more likely to have lesions smaller than 2.5 cm compared with Group A. Analysis of covariance demonstrated that the differences in outcome between the groups remained significant even with adjustment for the variation in duration of seizures (p = 0.0006) and size of tumor (p = 0.0001). Based on this study, the authors found that the probable relief from seizures caused by a temporal lobe lesion is greater if the region of epileptogenicity, usually the amygdalohippocampal complex, is resected along with the tumor in a temporal lobectomy.


Neuroprotective mechanism of BNG-1 against focal cerebral ischemia: a neuroimaging and neurotrophin study.
BNG-1 is a herb complex used in traditional Chinese medicine to treat stroke. In this study, we attempted to identify the neuroprotective mechanism of BNG-1 by using neuroimaging and neurotrophin analyses of a stroke animal model. Rats were treated with either saline or BNG-1 for 7 d after 60-min middle cerebral artery occlusion by filament model. The temporal change of magnetic resonance (MR) imaging of brain was studied using a 7 Tesla MR imaging (MRI) system and the temporal expressions of neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) in brain were analyzed before operation and at 4 h, 2 d, and 7 d after operation. Compared with the saline group, the BNG-1 group exhibited a smaller infarction volume in the cerebral cortex in T2 image from as early as 4 h to 7 d, less edema in the cortex in diffusion weighted image from 2 to 7 d, earlier reduction of postischemic hyperperfusion in both the cortex and striatum in perfusion image at 4 h, and earlier normalization of the ischemic pattern in the striatum in susceptibility weighted image at 2 d. NT-3 and BDNF levels were higher in the BNG-1 group than the saline group at 7 d. We concluded that the protective effect of BNG-1 against cerebral ischemic injury might act through improving cerebral hemodynamics and recovering neurotrophin generation.


Clustered functional MRI of overt speech production.
To investigate the neural network of overt speech production, event-related fMRI was performed in 9 young healthy adult volunteers. A clustered image acquisition technique was chosen to minimize speech-related movement artifacts. Functional images were acquired during the production of oral movements and of speech of increasing complexity (isolated vowel as well as monosyllabic and trisyllabic utterances). This imaging technique and behavioral task enabled depiction of the articulo-phonologic network of speech production from the supplementary motor area at the cranial end to the red nucleus at the caudal end. Speaking a single vowel and performing simple oral movements involved very similar activation of the cortical and subcortical motor systems. More complex, polysyllabic utterances were associated with additional activation in the bilateral cerebellum, reflecting increased demand on speech motor control, and additional activation in the bilateral temporal cortex, reflecting the stronger involvement of phonologic processing.


Use of thermography to monitor sole haemorrhages and temperature distribution over the claws of dairy cattle.
Subclinical laminitis, an early pathological event in the development of many claw diseases, is an important factor in the welfare and economics of high-producing dairy cows. However, the aetiology and pathogenesis of this complex claw disease are not well understood. The present study investigated to what extent thermographic examination of claws is able to give information about corium inflammation, and whether the technique may be used as a diagnostic tool for early detection of subclinical laminitis. Moreover, the temperature distribution over the individual main claws was investigated to obtain further knowledge about pressure distribution on the claws. For this purpose the claws of 123 cows were evaluated in the first week after calving as well as after the second month of lactation for presence of sole haemorrhages (a sign of subclinical laminitis). Furthermore, the ground contact area was analysed by thermography. Sole haemorrhages were significantly increased by the second month of lactation. Thermography showed clear differences between the claws of the front limbs and hindlimbs, as well as between lateral and medial claws. Although the distribution of sole haemorrhages was consistent with the pattern of the temperature distribution over the main claws, no clear correlation was found between the claw temperature after calving and the visible laminitis-like changes (sole haemorrhages) eight weeks later.


Yoga for asthma.
Asthma is a common chronic inflammatory disorder affecting about 300 million people worldwide. As a holistic therapy, yoga has the potential to relieve both the physical and psychological suffering of people with asthma, and its popularity has expanded globally. A number of clinical trials have been carried out to evaluate the effects of yoga practice, with inconsistent results. To assess the effects of yoga in people with asthma. We systematically searched the Cochrane Airways Group Register of Trials, which is derived from systematic searches of bibliographic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, AMED, and PsycINFO, and handsearching of respiratory journals and meeting abstracts. We also searched PEDro. We searched ClinicalTrials.gov and the WHO ICTRP search portal. We searched all databases from their inception to 22 July 2015, and used no restriction on language of publication. We checked the reference lists of eligible studies and relevant review articles for additional studies. We attempted to contact investigators of eligible studies and experts in the field to learn of other published and unpublished studies. We included randomised controlled trials (RCTs) that compared yoga with usual care (or no intervention) or sham intervention in people with asthma and reported at least one of the following outcomes: quality of life, asthma symptom score, asthma control, lung function measures, asthma medication usage, and adverse events. We extracted bibliographic information, characteristics of participants, characteristics of interventions and controls, characteristics of methodology, and results for the outcomes of our interest from eligible studies. For continuous outcomes, we used mean difference (MD) with 95% confidence interval (CI) to denote the treatment effects, if the outcomes were measured by the same scale across studies. Alternatively, if the outcomes were measured by different scales across studies, we used standardised mean difference (SMD) with 95% CI. For dichotomous outcomes, we used risk ratio (RR) with 95% CI to measure the treatment effects. We performed meta-analysis with Review Manager 5.3. We used the fixed-effect model to pool the data, unless there was substantial heterogeneity among studies, in which case we used the random-effects model instead. For outcomes inappropriate or impossible to pool quantitatively, we conducted a descriptive analysis and summarised the findings narratively. We included 15 RCTs with a total of 1048 participants. Most of the trials were conducted in India, followed by Europe and the United States. The majority of participants were adults of both sexes with mild to moderate asthma for six months to more than 23 years. Five studies included yoga breathing alone, while the other studies assessed yoga interventions that included breathing, posture, and meditation. Interventions lasted from two weeks to 54 months, for no more than six months in the majority of studies. The risk of bias was low across all domains in one study and unclear or high in at least one domain for the remainder.There was some evidence that yoga may improve quality of life (MD in Asthma Quality of Life Questionnaire (AQLQ) score per item 0.57 units on a 7-point scale, 95% CI 0.37 to 0.77; 5 studies; 375 participants), improve symptoms (SMD 0.37, 95% CI 0.09 to 0.65; 3 studies; 243 participants), and reduce medication usage (RR 5.35, 95% CI 1.29 to 22.11; 2 studies) in people with asthma. The MD for AQLQ score exceeded the minimal clinically important difference (MCID) of 0.5, but whether the mean changes exceeded the MCID for asthma symptoms is uncertain due to the lack of an established MCID in the severity scores used in the included studies. The effects of yoga on change from baseline forced expiratory volume in one second (MD 0.04 litres, 95% CI -0.10 to 0.19; 7 studies; 340 participants; I(2) = 68%) were not statistically significant. Two studies indicated improved asthma control, but due to very significant heterogeneity (I(2) = 98%) we did not pool data. No serious adverse events associated with yoga were reported, but the data on this outcome was limited. We found moderate-quality evidence that yoga probably leads to small improvements in quality of life and symptoms in people with asthma. There is more uncertainty about potential adverse effects of yoga and its impact on lung function and medication usage. RCTs with a large sample size and high methodological and reporting quality are needed to confirm the effects of yoga for asthma.


Induced paternal effects mimic cytoplasmic incompatibility in Drosophila.
Wolbachia is an intracellular microbe found in a wide diversity of arthropod and filarial nematode hosts. In arthropods these common bacteria are reproductive parasites that manipulate central elements of their host's reproduction to increase their own maternal transmission in one of several ways. Cytoplasmic incompatibility (CI) is one such manipulation where sperm are somehow modified in infected males and this modification must be rescued by the presence of the same bacterial strain in the egg for normal development to proceed. The molecular mechanisms involved in the expression of CI are unknown. Here we show that Wolbachia infection results in increased mRNA and protein expression of the Drosophila simulans nonmuscle myosin II gene zipper. Induced overexpression of zipper in Wolbachia-free transgenic D. melanogaster males results in paternal-effect lethality that mimics the fertilization defects associated with CI. Likewise, overexpression of the tumor suppressor gene, lethal giant larvae [l(2)gl], results in egg lethality and a CI phenotype. Stoichiometric levels of zipper and l(2)gl are required for proper segregation of cellular determinants during neuroblast stem cell division. Taken together these results form the basis of a working hypothesis whereby Wolbachia induces paternal effects in sperm by manipulating the expression of key regulators of cytoskeletal activity during spermatogenesis.


Synthesis and reactivity of mononuclear iron models of [Fe]-hydrogenase that contain an acylmethylpyridinol ligand.
[Fe]-hydrogenase has a single iron-containing active site that features an acylmethylpyridinol ligand. This unique ligand environment had yet to be reproduced in synthetic models; however the synthesis and reactivity of a new class of small molecule mimics of [Fe]-hydrogenase in which a mono-iron center is ligated by an acylmethylpyridinol ligand has now been achieved. Key to the preparation of these model compounds is the successful C-O cleavage of an alkyl ether moiety to form the desired pyridinol ligand. Reaction of solvated complex [(2-CH2CO-6-HOC5H3N)Fe(CO)2(CH3CN)2](+)(BF4)(-) with thiols or thiophenols in the presence of NEt3 yielded 5-coordinate iron thiolate complexes. Further derivation produced complexes [(2-CH2CO-6-HOC5H3N)Fe(CO)2(SCH2CH2OH)] and [(2-CH2CO-6-HOC5H3N)Fe(CO)2(CH3COO)], which can be regarded as models of FeGP cofactors of [Fe]-hydrogenase extracted by 2-mercaptoethanol and acetic acid, respectively. When the derivative complexes were treated with HBF4 ⋅Et2O, the solvated complex was regenerated by protonation of the thiolate ligands. The reactivity of several models with CO, isocyanide, cyanide, and H2 was also investigated.


Serum cytokines as biomarkers for age-related macular degeneration.
This study evaluates the potential of serum pro-inflammatory cytokines as AMD biomarkers. Serum samples from 30 age-related macular degeneration (AMD) patients and 15 age-matched controls were examined for 16 inflammatory cytokines using multiplex ELISA. Patients were divided into three subgroups (improvement/no change/deterioration during anti-VEGF treatment) by OCT and funduscopy, and correlated to the cytokine levels. Serum concentrations of IL-1α, IL-1β, IL-4, IL-5, IL-10, IL-13, and IL-17 were significantly higher in AMD patients than in controls. None of the co-variables expressed a significant effect on the tested cytokines. Only IL-1a and IL-17 showed a statistically significant difference between groups (improved, unchanged, deteriorated) as determined by one-way ANOVA. Patients with increased macular thickness during treatment showed significantly lower levels of IL-17 compared to improved cases and to unchanged cases (p = 0.004, 0.03 respectively, Dunnett's T3 post hoc multiple test). TNF-α was significantly higher in improved cases compared to deteriorated cases (p =0.03, Dunnett's T3 post hoc multiple test). IL-17 was a significant predictor for macular oedema using linear regression (β = -0.888, p <0.05). Elevation of IL-1α, IL-1β, IL-4, IL-5, IL-10, IL-13, and IL-17 in the serum of AMD patients supports the hypothesis of AMD as an inflammatory disease. Patients with high IL-17 and TNF-α serum levels were more likely to have a favourable course under VEGF therapy. These cytokines may be used as easy-to-obtain biomarkers.


Rice yields decline with higher night temperature from global warming.
The impact of projected global warming on crop yields has been evaluated by indirect methods using simulation models. Direct studies on the effects of observed climate change on crop growth and yield could provide more accurate information for assessing the impact of climate change on crop production. We analyzed weather data at the International Rice Research Institute Farm from 1979 to 2003 to examine temperature trends and the relationship between rice yield and temperature by using data from irrigated field experiments conducted at the International Rice Research Institute Farm from 1992 to 2003. Here we report that annual mean maximum and minimum temperatures have increased by 0.35 degrees C and 1.13 degrees C, respectively, for the period 1979-2003 and a close linkage between rice grain yield and mean minimum temperature during the dry cropping season (January to April). Grain yield declined by 10% for each 1 degrees C increase in growing-season minimum temperature in the dry season, whereas the effect of maximum temperature on crop yield was insignificant. This report provides a direct evidence of decreased rice yields from increased nighttime temperature associated with global warming.


Synthesis of Five- and Six-Membered N-Phenylacetamido Substituted Heterocycles as Formyl Peptide Receptor Agonists.
Preclinical Research Formyl peptide receptors (FPRs) are G-protein-coupled receptors that play an important role in the regulation of inflammatory process and cellular dysfunction. In humans, three different isoforms are expressed (FPR1, FPR2, and FPR3). FPR2 appears to be directly involved in the resolution of inflammation, an active process carried out by specific pro-resolving mediators that modulate specific receptors. Previously, we identified 2-arylacetamido pyridazin-3(2H)-ones as FPR1- or FPR2-selective agonists, as well as a large number of mixed-agonists for the three isoforms. Here, we report a new series of 2-arylacetamido pyridazinones substituted at position 5 and their development as FPR agonists. We also synthesized a new series of 2-oxothiazolones bearing a 4-bromophenylacetamido fragment, which was fundamental for activity in the pyridazinone series. The compounds of most interest were 4a, a potent, mixed FPR agonist recognized by all three isotypes (FPR1 EC50 = 19 nM, FPR2 EC50 = 43 nM, FPR3 EC50 = 40 nM), and 4b, which had potent activity and a preference for FPR2 (EC50 = 13 nM). These novel compounds may represent valuable tools for studying FPR activation and signaling. Drug Dev Res 78 : 49-62, 2017. © 2016 Wiley Periodicals, Inc.


A critical evaluation of the role of alternative oxidase in the performance of strobilurin and related fungicides acting at the Qo site of complex III.
Mitochondrial respiration conserves energy by linking NADH oxidation and electron-coupled proton translocation with ATP synthesis, through a core pathway involving three large protein complexes. Strobilurin fungicides block electron flow through one of these complexes (III), and disrupt energy supply. Despite an essential need for ATP throughout fungal disease development, strobilurins are largely preventative; indeed some diseases are not controlled at all, and several pathogens have quickly developed resistance. Target-site variation is not the only cause of these performance difficulties. Alternative oxidase (AOX) is a strobilurin-insensitive terminal oxidase that allows electrons from ubiquinol to bypass Complex III. Its synthesis is constitutive in some fungi but in many others is induced by inhibition of the main pathway. AOX provides a strobilurin-insensitive pathway for oxidation of NADH. Protons are pumped as electrons flow through Complex I, but energy conservation is less efficient than for the full respiratory chain. Salicylhydroxamic acid (SHAM) is a characteristic inhibitor of AOX, and several studies have explored the potentiation of strobilurin activity by SHAM. We present a kinetic-based model which relates changes in the extent of potentiation during different phases of disease development to a changing importance of energy efficiency. The model provides a framework for understanding the varying efficacy of strobilurin fungicides. In many cases, AOX can limit strobilurin effectiveness once an infection is established, but is unable to interfere significantly with strobilurin action during germination. A less stringent demand for energy efficiency during early disease development could lead to insensitivity towards this class of fungicides. This is discussed in relation to Botrytis cinerea, which is often poorly controlled by strobilurins. Mutations with a similar effect may explain evidence implicating AOX in resistance development in normally well-controlled plant pathogens, such as Venturia inaequalis.


Diagnostic significance of Neospora caninum DNA detected by PCR in cattle serum.
A nested PCR that successfully detected Neospora caninum DNA in serum of cattle was used for investigation of selected abortion cases and in a study of healthy pregnant cows at an abattoir. N. caninum DNA was not detected in serum from antibody positive dams that aborted due to N. caninum, but was present in serum of some antibody negative dams that aborted due to other causes. N. caninum DNA was also found in the serum of about half of the animals that aborted of undetermined cause, but was not detected in cow sera from two beef cattle herds in Western Australia with no recent history of abortion. In the abattoir study of 79 dams and their foetuses N. caninum DNA was found in serum of 3 dams and in material from 11 foetuses. The majority of the cows and all foetuses were antibody negative. Our findings suggest that there is no obvious relationship between the presence or absence of N. caninum DNA in serum and the presence of antibodies to N. caninum in dams, the presence of N. caninum DNA in foetuses or abortion due to N. caninum. This is the first report of the detection of N. caninum DNA in serum of cattle rather than the white blood cell fraction. It indicates the presence of free tachyzoites and/or parasite DNA in circulation. The results suggest that persistent infection in the absence of antibodies is a possible outcome of N. caninum infection. Infection of foetuses in the absence of antibodies supports the possibility of persistent infection due to immunotolerance to an early in utero infection. It is therefore important to test for N. caninum DNA as well as antibodies for the detection of exposed and/or infected animals. However, the presence or absence of N. caninum antibodies or DNA did not support nor exclude N. caninum as the cause of abortion. Additional criteria are required for a positive diagnosis of abortion caused by N. caninum.


The soybean cultivar specificity gene nolX is present, expressed in a nodD-dependent manner, and of symbiotic significance in cultivar-nonspecific strains of Rhizobium (Sinorhizobium) fredii.
Rhizobium (now Sinorhizobium) fredii is a symbiotic nitrogen-fixing bacterium that can nodulate soybean in a cultivar-specific manner. This process is governed by a set of negatively acting nodulation genes termed nolXWBTUV. These genes prevent R. fredii strain USDA257 from infecting soybean cultivars such as McCall, but they do not block nodulation of cultivar Peking. R. fredii strain USDA191 contains DNA sequences that hybridize to nolXWBTUV, yet it forms normal nitrogen-fixing nodules on both McCall and Peking soybean. These sequences were isolated and their structure and function examined in comparison to nolXWBTUV of strain USDA257. Restriction maps of the two loci are identical, as is a 2-4 kb DNA sequence that corresponds to nolX and its promoter region. Expression of nolX by strain USDA191 is flavonoid-dependent in culture and readily detectable in nodules. The gene is not inducible in a mutant of strain USDA191 that lacks the regulatory nodD1 gene, and its expression is greatly attenuated in a nodD2 mutant. nolX is also present and flavonoid-inducible in HH103, a second R. fredii strain that nodulates McCall soybean normally. Inactivation of nolX in strain HH103, USDA191 or USDA257 leads to retardation of initial nodulation rates on soybean cultivars such as Peking and to acquisition of the capacity to form nitrogen-fixing nodules on two species of Erythrina. nolX is thus of symbiotic significance in all three strains, even though it regulates soybean cultivar specificity only in strain USDA257.


Overeating among adolescents: prevalence and associations with weight-related characteristics and psychological health.
To assess the prevalence of overeating among adolescents and to examine associations between overeating and sociodemographic characteristics, weight status, dieting behaviors, body satisfaction, depressive mood, self-esteem, and suicide. A school-based sample of 4746 boys and girls in public middle and high schools in Minnesota completed the Project EAT (Eating Among Teens) survey and anthropometric measurements of height and weight. Overall, 17.3% of girls and 7.8% of boys reported objective overeating in the past year. Youths who engaged in overeating were more likely to be overweight or obese, to have dieted in the past year, to be trying to lose weight currently, and to report that weight and shape are very important to their overall feelings about self. Youths who met criteria for binge eating syndrome (high frequency of objective overeating with loss of control and distress regarding the binge eating) scored significantly lower on measures of body satisfaction and self-esteem and higher on a measure of depressive mood than those who reported either subclinical or no binge eating. Overeating was associated with suicide risk; more than one fourth of girls (28.6%) and boys (27.8%) who met criteria for binge eating syndrome reported that they had attempted suicide. Overeating among adolescents is associated with a number of adverse behaviors and negative psychological experiences. As the current study is cross-sectional, it is not possible to ascertain cause and effect. Future research should seek to identify whether objective overeating is an early warning sign of additional psychological distress or is a potential consequence of compromised psychological health. Clinical implications are discussed.