Comparison of patterns of allergen sensitization among inner-city Hispanic and African American children with asthma.
Among Hispanics, the largest minority ethnic group in the United States, asthma prevalence is increasing, particularly in inner-city neighborhoods. Although allergen sensitization among asthmatic African Americans has been extensively studied, similar details are not available for Hispanic children. To examine patterns of allergen sensitization, including the association with illness severity, in asthmatic children overall and in Hispanic and African American children living in a socioeconomically disadvantaged area of New York City. A retrospective medical record review of asthmatic children attending a community hospital in the South Bronx area of New York City was performed. Information abstracted included demographics, asthma severity classification, reported exposures to indoor allergens, and results of allergy testing. Among 384 children in the analysis, 270 (70.3%) were Hispanic and 114 (29.7%) were African American. Sensitization to indoor and outdoor allergens, respectively, did not differ between Hispanic (58.5% and 27.0%) and African American (58.8% and 32.6%) children. Allergen sensitization exhibited a direct, significant association with asthma severity for indoor allergens for the 2 ethnic groups combined and for Hispanics separately but not between asthma severity and outdoor allergens (P < .01). No correlation was found between self-reported allergen exposure and sensitization. Patterns of allergen sensitization among inner-city Hispanic asthmatic children resemble those among African American children, a finding that is likely explained by the similarity in levels of environmental exposures. With the increasing prevalence of asthma among inner-city Hispanic children, skin testing should be used frequently for objective evaluation of asthma in this ethnic group.


Comprehensive diabetes management program for poorly controlled Hispanic type 2 patients at a community health center.
Technology and improved care coordination models can help diabetes educators and providers meet national care standards and provide culturally sensitive diabetes education that may improve diabetes outcomes. The purpose of the study was to evaluate the clinical usefulness of a nurse-led diabetes care program (Comprehensive Diabetes Management Program, CDMP) for poorly controlled Hispanic type 2 diabetes (T2DM) patients in an urban community health center setting. Patients were randomized to the intervention condition (IC; n = 21) or an attention control condition (AC; n = 18). IC and AC conditions were compared on rates of adherence to national clinical practice guidelines (blood glucose, blood pressure, foot exam, eye exam), and levels of diabetes distress, depression, and treatment satisfaction. IC patients had a significant improvement in A1C from baseline to 12-month follow-up compared with AC (-1.6% ± 1.4% versus -0.6% ± 1.1%; P = .01). The proportion of IC patients meeting clinical goals at follow-up tended to be higher than AC for A1c (IC = 45%; AC = 28%), systolic blood pressure (IC = 55%; AC = 28%), eye screening (IC = 91%; AC = 78%), and foot screening, (IC = 86%; AC = 72%). Diabetes distress and treatment satisfaction also showed greater improvement for IC than AC (P = .05 and P = .06, respectively), with no differences for depression. The CDMP intervention was more effective than an attention control condition in helping patients meet evidence-based guidelines for diabetes care.


Knowledge and use of finasteride for the prevention of prostate cancer.
The knowledge about and use of chemopreventive agents for prostate cancer by physicians has not been described. The Prostate Cancer Prevention Trial (PCPT) showed that finasteride was effective in reducing the incidence of prostate cancer. We examined the influence of the PCPT on finasteride prescribing within the Veterans Health Administration (VHA). We assessed trends on monthly new and total prescriptions for finasteride filled within the VHA from January 2000 to December 2005. Additionally, all VHA urologists and a random sample of VHA primary care physicians (PCP) were surveyed about their use of finasteride. The number of men starting finasteride grew over the study period. Publication of the PCPT was not significantly associated with any change in this pattern (P = 0.45). Fifty-seven percent of urologists and 40% of PCPs endorsed prescribing finasteride more frequently in 2006 than 5 years prior. However, among those who reported changing prescribing patterns, fewer than 2% reported being influenced by the PCPT. Sixty-four percent of urologists and 80% of PCPs never prescribe finasteride for prostate cancer chemoprevention; 55% of urologists cited concerns of inducing high-grade tumors, whereas 52% of PCPs did not know it could be used for chemoprevention. The number of men starting finasteride in the VHA increased over time, but the change did not seem to be due to increased use of finasteride for chemoprevention. Publication of the PCPT seemed to have little influence over the study period. Physicians may not readily accept the use of chemopreventive agents for prostate cancer.


Guideline of guidelines: testosterone therapy for testosterone deficiency.
We analysed the guidelines for testosterone therapy (TTh) produced by major international medical societies including: the American Urological Association, European Association of Urology, American Association of Clinical Endocrinologists, British Society for Sexual Medicine, Endocrine Society, International Society for Sexual Medicine, and the International Society for the Study of the Aging Male, and compared their recommendations. All the organisations were in general agreement concerning the following key points: Only men meeting the criteria for testosterone deficiency (TD) should be treated. Consider screening asymptomatic men with certain conditions that increase the risk of TD. Exogenous TTh causes impairment of spermatogenesis. There is no evidence that TTh causes prostate cancer. Men on TTh require careful laboratory monitoring.


14th International HLA and Immunogenetics Workshop Prospective Chronic Rejection Project: a three-year follow-up analysis.
The three-year follow-up of 4,144 patients of the 14th International Workshop Prospective Chronic Rejection study has reinforced the evidence that post-transplant HLA antibodies are predictive of long-term graft loss. Three years after a single testing for HLA antibodies, 10% of kidney recipients who were antibody-positive had lost their grafts, in contrast to only 5% of antibody-negative patients (p<0.0001). The adverse effect of post-transplant antibodies on graft survival was also observed in lung, heart, and liver transplants. Donor-specific antibodies and 'strong' non-DSA had stronger association with graft loss than 'moderate' non-DSA. Periodic antibody monitoring, combined with specificity and strength analysis, would help in the early identification of allograft recipients who are at high risk of graft failure.


Effect of intracameral cefuroxime on fibrinous uveitis after pediatric cataract surgery.
To determine whether intracameral cefuroxime reduces postoperative fibrin formation after pediatric cataract surgery. Children aged 3 months to 10 years with bilateral congenital or developmental cataracts who underwent surgery between February and July 2008 were eligible for inclusion in this prospective double-masked study. The same surgical technique was used in each eye. The intraocular lens was placed in either the bag or sulcus in both eyes. The same intraocular lens type was used in both eyes (polymethylmethacrylate). One eye was randomized to receive intracameral cefuroxime at the end of surgery and the fellow eye received saline. The surgeon was masked to the treatment assignment. The amount of fibrin formation in the anterior chamber of each eye was assessed by a masked grader on the fourth postoperative day. Seventy eyes of 35 children were included in the study. Fibrin formation was noted on the fourth postoperative day in 14 of 70 eyes (20%), 7 in the cefuroxime group and 7 in the saline group. The mean fibrin score was 0.57 ± 1.31 in the cefuroxime group and 0.49 ± 1.07 in the saline group. There was no statistically significant difference in the amount of fibrin formation between groups (P = .857, Wilcoxon ranked signs test). Intracameral cefuroxime did not significantly reduce postoperative fibrin formation in this study. Fibrin formation does not appear to be due to bacterial contamination in most cases of pediatric cataract surgery.


The TMK1 gene from Arabidopsis codes for a protein with structural and biochemical characteristics of a receptor protein kinase.
Genomic and cDNA clones that code for a protein with structural and biochemical properties similar to the receptor protein kinases from animals were obtained from Arabidopsis. Structural features of the predicted polypeptide include an amino-terminal membrane targeting signal sequence, a region containing blocks of leucine-rich repeat elements, a single putative membrane spanning domain, and a characteristic serine/threonine-specific protein kinase domain. The gene coding for this receptor-like transmembrane kinase was designated TMK1. Portions of the TMK1 gene were expressed in Escherichia coli, and antibodies were raised against the recombinant polypeptides. These antibodies immunodecorated a 120-kD polypeptide present in crude extracts and membrane preparations. The immunodetectable band was present in extracts from leaf, stem, root, and floral tissues. The kinase domain of TMK1 was expressed as a fusion protein in E. coli, and the purified fusion protein was found capable of autophosphorylation on serine and threonine residues. The possible role of the TMK1 gene product in transmembrane signaling is discussed.


Tube-Wise Diagnostic Microarray for the Multiplex Characterization of the Complex Plant Pathogen Ralstonia solanacearum.
Ralstonia solanacearum is a well-known agricultural and ecological threat worldwide. The complexity of the R. solanacearum species complex (Rssc) represents a challenge for the accurate characterization of epidemiological strains by official services and research laboratories. The majority of protocols only focus on a narrow range of strains; however, this species complex includes strains that represent major constraints and are under strict regulation. The main drawback associated with the current methods of detecting and characterizing Rssc strains is their reliance on combining different protocols to properly characterize the strains at the ecotype level, which require time and money. Therefore, we used microarray technology (ArrayTube) to develop a standard protocol, which characterizes 17 major groups of interest in the Rssc, in a single multiplex reaction. These 17 majors groups are linked with a phylogenetic assignation (phylotypes, sequevars), but also with an ecotype assignation associated with a range of hosts (e.g., brown rot, Moko). Probes were designed with a 50-mer length constraint and thoroughly evaluated for any flaws or secondary structures. The strains are characterized based on a DNA extraction from pure culture. Validation data showed strong intra-repeatability, inter-repeatability, and reproducibility as well as good specificity. A hierarchical analysis of the probe groups is suitable for an accurate characterization. Compared with single marker detection tests, the method described in this paper addresses efficiently the issue of combining several tests by testing a large number of phylogenetic markers in a single reaction assay. This custom microarray (RsscAT) represents a significant improvement in the epidemiological monitoring of Rssc strains worldwide, and it has the potential to provide insights for phylogenetic incongruence of Rssc strains based on the host of isolation and may be used to indicate potentially emergent strains.


Hepatocellular Carcinoma: a Comprehensive Review of Biomarkers, Clinical Aspects, and Therapy
Hepatocellular carcinoma (HCC) is a cause of several deaths related to cancer worldwidely. In early stage, curative treatments such as surgical resection, liver transplant and local ablation can improve the patient ´s survival. However, the disease is detected in advanced stage; moreover some available therapies are restricted to palliative care and local treatment. Early detections of HCC and adequate therapy are crucial to increase survival as well as to improve the patient´s quality of life. Therefore, researchers have been investigating molecular biomarkers with high sensibility and reliability as Golgi 73 protein (GP73), Glypican-3 (GPC3), Osteopontin (OPN), microRNAs and others. MicroRNAs can regulate important pathways on carcinogenesis, as tumor angiogenesis and progression. So, they can be considered as possible markers of prognosis in HCC, and therapeutic target for this tumor type. In this review, we discuss the recent advances related to the cause (highlighting the main risk factors), treatment, biomarkers, clinic aspects, and outcome in hepatocellular carcinoma.


IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP).
Autism spectrum disorder (ASD) was once considered to be highly associated with intellectual disability and to show a characteristic IQ profile, with strengths in performance over verbal abilities and a distinctive pattern of 'peaks' and 'troughs' at the subtest level. However, there are few data from epidemiological studies. Comprehensive clinical assessments were conducted with 156 children aged 10-14 years [mean (s.d.)=11.7 (0.9)], seen as part of an epidemiological study (81 childhood autism, 75 other ASD). A sample weighting procedure enabled us to estimate characteristics of the total ASD population. Of the 75 children with ASD, 55% had an intellectual disability (IQ<70) but only 16% had moderate to severe intellectual disability (IQ<50); 28% had average intelligence (115>IQ>85) but only 3% were of above average intelligence (IQ>115). There was some evidence for a clinically significant Performance/Verbal IQ (PIQ/VIQ) discrepancy but discrepant verbal versus performance skills were not associated with a particular pattern of symptoms, as has been reported previously. There was mixed evidence of a characteristic subtest profile: whereas some previously reported patterns were supported (e.g. poor Comprehension), others were not (e.g. no 'peak' in Block Design). Adaptive skills were significantly lower than IQ and were associated with severity of early social impairment and also IQ. In this epidemiological sample, ASD was less strongly associated with intellectual disability than traditionally held and there was only limited evidence of a distinctive IQ profile. Adaptive outcome was significantly impaired even for those children of average intelligence.


An agenda for quality improvement in forensic mental health consultation.
Recent developments in quality assurance in health care have embraced the total quality management approach to industrial quality control. Setting a goal of "continuous quality improvement" for medical care, this approach features special attention to the process and systems of care provision. Applying this approach to the specialty of forensic mental health consultation yields a variety of potential ways of improving care, by articulating common problems in the consultation process that might respond to the total quality management approach. These problems include the setting of appropriate goals for forensic evaluation, and selecting cases for attention on the basis of those goals; determining appropriate standards for thoroughness and validity in the use of evaluation techniques; and establishing clear expectations regarding the provision of mental health services beyond the consultation process itself. Creating interdisciplinary teams at various levels of administration of trial courts and mental health agencies can provide contexts for reviewing cases, with the aim of discovering problems in these areas, educating professionals across boundaries about sources of problems, and developing clearer and more consistent standards of practice to reduce problems and improve quality of service.


Ancient diversity of splicing motifs and protein surfaces in the wild emmer wheat (Triticum dicoccoides) LR10 coiled coil (CC) and leucine-rich repeat (LRR) domains.
In this study, we explore the diversity and its distribution along the wheat leaf rust resistance protein LR10 three-dimensional structure. Lr10 is a leaf rust resistance gene encoding a coiled coil-nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR) class of protein. Lr10 was cloned and sequenced from 58 accessions representing diverse habitats of wild emmer wheat in Israel. Nucleotide diversity was very high relative to other wild emmer wheat genes (π= 0.029). The CC domain was found to be the most diverse domain and subject to positive selection. Superimposition of the diversity on the CC three-dimensional structure showed that some of the variable and positively selected residues were solvent exposed and may interact with other proteins. The LRR domain was relatively conserved, but showed a hotspot of amino acid variation between two haplotypes in the ninth repeat. This repeat was longer than the other LRRs, and three-dimensional modelling suggested that an extensive α helix structure was formed in this region. The two haplotypes also differed in splicing regulation motifs. In genotypes with one haplotype, an intron was alternatively spliced in this region, whereas, in genotypes with the other haplotype, this intron did not splice at all. The two haplotypes are proposed to be ancient and maintained by balancing selection.


Standards for prostate biopsy.
A variety of techniques have emerged for the optimization of prostate biopsy. In this review, we summarize and critically discuss the most recent developments regarding the optimal systematic biopsy and sampling labeling along with multiparametric MRI and magnetic resonance-targeted biopsies. The use of 10-12-core-extended sampling protocols increases cancer detection rates compared with traditional sextant sampling and reduces the likelihood that patients will require a repeat biopsy, ultimately allowing more accurate risk stratification without increasing the likelihood of detecting insignificant cancers. As the number of cores increases above 12 cores, the increase in diagnostic yield becomes marginal. However, the limitations of this technique include undersampling, oversampling, and the need for repetitive biopsy. MRI and magnetic resonance-targeted biopsies have demonstrated superiority over systematic biopsies for the detection of clinically significant disease and representation of disease burden, while deploying fewer cores and may have applications in men undergoing initial or repeat biopsy and those with low-risk cancer on or considering active surveillance. A 12-core systematic biopsy that incorporates apical and far-lateral cores in the template distribution allows maximal cancer detection, avoidance of a repeat biopsy while minimizing the detection of insignificant prostate cancers. MRI-guided prostate biopsy has an evolving role in both initial and repeat prostate biopsy strategies, as well as active surveillance, potentially improving sampling efficiency, increasing the detection of clinically significant cancers, and reducing the detection of insignificant cancers.


Structure and reactivity of "unusual" N-heterocyclic carbene (NHC) palladium complexes synthesized from imidazolium salts.
The reaction between palladium acetate and IMES.HCl leads to the formation of a novel palladium complex. The X-ray crystal structure analysis reveals that the palladium is C(2) bound to one NHC ligand (the normal binding mode), whereas the second ligand is attached through the C(5) carbon of the second imidazolium. The metalation site on the imidazolium salt is strongly influenced by the presence of base. Furthermore, the binding mode of the NHC to Pd is shown to substantially affect the catalytic behavior of the palladium complexes in cross-coupling reactions.


Genotypic and phenotypic spectrum of CCDC141 variants in a Chinese cohort with congenital hypogonadotropic hypogonadism.
To identify CCDC141 variants in a large Chinese cohort with congenital hypogonadotropic hypogonadism (CHH) and to assess the contribution of CCDC141 to CHH. Detailed phenotyping was conducted in CHH patients with CCDC141 variants and co-segregation analysis was performed, when possible. Whole-exome sequencing was performed in 177 CHH patients and 450 unrelated, ethnically matched controls from China. Seven novel CCDC141 rare sequencing variants (RSVs) were identified in 12 CHH pedigrees. Four of the variants were private mutations; however, p.Q409X, p.Q871X and p.G1488S were identified in more than one patient. Up to 75% (9/12) of patients had mutations in other CHH-associated genes, which is significantly higher than CHH patients without CCDC141 RSVs. The co-segregation analysis for eight CHH families showed that 75% (6/8) CCDC141 RSVs were inherited from their fertile parents. Over half (58.3%, 8/18) of the patients exhibited other clinical deformities in addition to hypogonadism. One patient harbouring a CCDC141 RSV showed a reversal of CHH after sex-steroid replacement. Our results broaden the genotypic spectrum of CCDC141 in CHH, as CCDC141 RSVs alone do not appear sufficient to cause CHH. The phenotypic spectrum in patients with CCDC141 RSVs is much wider than originally believed.


A Comparison of the Perceptual and Technical Demands of Tennis Training, Simulated Match Play, and Competitive Tournaments.
High-performance tennis environments aim to prepare athletes for competitive demands through simulated-match scenarios and drills. With a dearth of direct comparisons between training and tournament demands, the current investigation compared the perceptual and technical characteristics of training drills, simulated match play, and tournament matches. Data were collected from 18 high-performance junior tennis players (gender: 10 male, 8 female; age 16 ± 1.1 y) during 6 ± 2 drill-based training sessions, 5 ± 2 simulated match-play sessions, and 5 ± 3 tournament matches from each participant. Tournament matches were further distinguished by win or loss and against seeded or nonseeded opponents. Notational analysis of stroke and error rates, winners, and serves, along with rating of perceived physical exertion (RPE) and mental exertion was measured postsession. Repeated-measures analyses of variance and effect-size analysis revealed that training sessions were significantly shorter in duration than tournament matches (P < .05, d = 1.18). RPEs during training and simulated match-play sessions were lower than in tournaments (P > .05; d = 1.26, d = 1.05, respectively). Mental exertion in training was lower than in both simulated match play and tournaments (P > .05; d = 1.10, d = 0.86, respectively). Stroke rates during tournaments exceeded those observed in training (P < .05, d = 3.41) and simulated-match-play (P < .05, d = 1.22) sessions. Furthermore, the serve was used more during tournaments than simulated match play (P < .05, d = 4.28), while errors and winners were similar independent of setting (P > .05, d < 0.80). Training in the form of drills or simulated match play appeared to inadequately replicate tournament demands in this cohort of players. Coaches should be mindful of match demands to best prescribe sessions of relevant duration, as well as internal (RPE) and technical (stroke rate) load, to aid tournament preparation.


Reduction of the cytosolic calcium activity in clonal insulin-releasing cells exposed to glucose.
The cytosolic Ca2+ activity of insulin-releasing clonal cells (RINm5F) was studied with the intracellular fluorescent indicator quin-2. When the extracellular Ca2+ concentration was 1 mM, the basal cytosolic Ca2+ activity was 101 +/- 5 nM. Depolarization with 25 mM K+ increased this Ca2+ activity to at least 318 nM, an effect completely reversed by the voltage-dependent channel blocker D-600. In the presence of K+ alone these channels appeared to have a half-life of 6.7 +/- 0.8 min. In contrast to the action of K+, exposure of the RINm5F cells to 4 mM glucose resulted in a reduction of the cytosolic Ca2+ activity. This effect was observed during K+ depolarization but was more pronounced under basal conditions when it amounted to 20%. The data provide the first direct evidence that glucose can decrease the cytosolic Ca2+ activity in beta-cells. Unlike the case in normal beta-cells the glucose effect on the voltage-dependent Ca2+ channels in the RINm5F cells is apparently not sufficient to overcome the intracellular buffering of Ca2+. A defective depolarization is therefore a probable cause of the failing insulin secretion of RINm5F cells exposed to glucose.


The KiVa antibullying program in primary schools in Chile, with and without the digital game component: study protocol for a randomized controlled trial.
Bullying is a major problem worldwide and Chile is no exception. Bullying is defined as a systematic aggressive behavior against a victim who cannot defend him or herself. Victims suffer social isolation and psychological maladjustment, while bullies have a higher risk for conduct problems and substance use disorders. These problems appear to last over time. The KiVa antibullying program has been evaluated in Finland and other European countries, showing preventive effects on victimization and self-reported bullying. The aims of this study are (1) to develop a culturally appropriate version of the KiVa material and (2) to test the effectiveness of the KiVa program, with and without the online game, on reducing experiences of victimization and bullying behavior among vulnerable primary schools in Santiago (Chile), using a cluster randomized controlled trial (RCT) design with three arms: (1) full KiVa program group, (2) partial KiVa (without online game) program group and (3) control group. This is a three-arm, single-blind, cluster randomized controlled trial (RCT) with a target enrolment of 1495 4th and 5th graders attending 13 vulnerable schools per arm. Students in the full and partial KiVa groups will receive universal actions: ten 2-h lessons delivered by trained teachers during 1 year; they will be exposed to posters encouraging them to support victims and behave constructively when witnessing bullying; and a person designated by the school authorities will be present in all school breaks and lunchtimes using a visible KiVa vest to remind everybody that they are in a KiVa school. KiVa schools also will have indicated actions, which consist of a set of discussion groups with the victims and with the bullies, with proper follow-up. Only full KiVa schools will also receive an online game which has the aim to raise awareness of the role of the group in bullying, increase empathy and promote strategies to support victimized peers. Self-reported victimization, bullying others and peer-reported bullying actions, psychological and academic functioning, and sense of school membership will be measured at baseline and 12 months after randomization. This is the first cluster RCT of the KiVa antibullying program in Latin America. ClinicalTrials.gov, Identifier: NCT02898324 . Registered on 8 September 2016.


Experiencing cancer treatment decision-making in managed care.
This paper is a report of a study to explore women's perceptions of and experiences with breast cancer treatment decision-making in managed care organizations (MCOs). Managed care organizations are the predominant form of employer-sponsored healthcare insurance in the United States of America. These healthcare financing entities minimize cost by streamlining healthcare delivery and may impose choice restrictions. The extent of these restrictions has not previously been studied from an in-depth patient perspective. A qualitative descriptive approach was adopted using interviews with a purposive sample of 14 managed care enrollees diagnosed with breast cancer at all stages. The data were collected between 2003 and 2005. Data analysis involved a reflexive process of transcript reading, categorization, data reduction and interpretation. The findings are presented as a single theme: 'decisional conflict in managed care', with two distinct categories: decisions regarding (1) the MCOs and (2) treatment. MCO selection was perceived to be limited by employer constraints, cost issues or healthcare plan providers. For study participants, selecting a MCO was less difficult than issues surrounding treatment decision-making. Women reported that their most important treatment-related decisions surrounded diagnosis and involved selecting a treatment facility and provider. Once a satisfactory facility and provider were selected, these women preferred to defer treatment decisions to their healthcare providers. Decision interventions should be focused on assisting women with provider and treatment facility selection early in diagnosis. Our findings might also serve as a basis for policy/practice changes to address healthcare financing limitations and to expand cancer treatment-related choices while providing desired treatment decision-making support.


Population dynamics of exploited fish stocks at low population levels.
Models of population dynamics in which per capita reproductive success declines at low population levels (variously known as depensation, the Allee effect, and inverse density-dependence) predict that populations can have multiple equilibria and may suddenly shift from one equilibrium to another. If such depensatory dynamics exist, reduced mortality may be insufficient to allow recovery of a population after abundance has been severely reduced by harvesting. Estimates of spawner abundance and number of surviving progeny for 128 fish stocks indicated only 3 stocks with significant depensation. Estimates of the statistical power of the tests strengthen the conclusion that depensatory dynamics are not apparent for fish populations at the levels studied.


Does perceived physical attractiveness in adolescence predict better socioeconomic position in adulthood? Evidence from 20 years of follow up in a population cohort study.
There is believed to be a 'beauty premium' in key life outcomes: it is thought that people perceived to be more physically attractive have better educational outcomes, higher-status jobs, higher wages, and are more likely to marry. Evidence for these beliefs, however, is generally based on photographs in hypothetical experiments or studies of very specific population subgroups (such as college students). The extent to which physical attractiveness might have a lasting effect on such outcomes in 'real life' situations across the whole population is less well known. Using longitudinal data from a general population cohort of people in the West of Scotland, this paper investigated the association between physical attractiveness at age 15 and key socioeconomic outcomes approximately 20 years later. People assessed as more physically attractive at age 15 had higher socioeconomic positions at age 36- in terms of their employment status, housing tenure and income - and they were more likely to be married; even after adjusting for parental socioeconomic background, their own intelligence, health and self esteem, education and other adult socioeconomic outcomes. For education the association was significant for women but not for men. Understanding why attractiveness is strongly associated with long-term socioeconomic outcomes, after such extensive confounders have been considered, is important.


Advances in the treatment of human T-cell lymphotropic virus type-I associated myelopathy.
Nearly 2-3% of those 10 to 20 million individuals infected with the Human T-cell lymphotropic virus type-1 (HTLV-1); are predisposed to developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is a neuro-inflammatory disease; differentiated from multiple sclerosis based on the presence of typical neurologic symptoms, confirmation of HTLV-1 infection, and other molecular biomarkers. A brief review of the epidemiology, host immune responses, and molecular pathogenesis of HAM/TSP is followed by detailed discussions about the host-related risk factors for developing HAM/TSP and success/failure stories of the attempted management strategies. Currently, there is no effective treatment for HAM/TSP. Anti-retroviral therapy, peculiar cytokines (IFN-α), some anti-oxidants, and allograft bone marrow transplantation have been used for treating these patients with limited success. Under current conditions, asymptomatic carriers should be examined periodically by a neurologist for early signs of spinal cord injury. Then it is crucial to determine the progress rate to adapt the best management plan for each patient. Corticosteroid therapy is most beneficial in those with acute myelitis. However, slow-progressing patients are best managed using a combination of symptomatic and physical therapy. Additionally, preventive measures should be taken to decrease further spread of HTLV-1 infection.


Lumbar facet joint arthritis is associated with more coronal orientation of the facet joints at the upper lumbar spine.
We retrospectively analyzed CT scans of 620 individuals, who presented to our traumatology department between 2008 and 2010. Facet joint (FJ) arthritis was present in 308 (49.7%) individuals with a mean grade of 1. It was seen in 27% of individuals ≤40 years and in 75% of individuals ≥41 years (P < 0.0001) as well as in 52% of females and 49% of males (P = 0.61). Mean FJ orientation was 30.4° at L2/3, 38.7° at L3/4, 47° at L4/5, and 47.3° at L5/S1. FJ arthritis was significantly associated with more coronal (increased degree) FJ orientation at L2/3 (P = 0.03) with a cutoff point at ≥32°. FJs were more coronally oriented (48.8°) in individuals ≤40 years and more sagittally oriented (45.6°) in individuals ≥41 years at L5/S1 (P = 0.01). Mean FJ asymmetry was 4.89° at L2/3, 6.01° at L3/4, 6.67° at L4/5, and 7.27° at L5/S1, without a significant difference for FJ arthritis. FJ arthritis is common, increases with age, and affects both genders equally. More coronally oriented FJs (≥32°) in the upper lumbar spine may be an individual risk factor for development of FJ arthritis.


Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy.
Membrane sphingolipids are metabolized to sphingosine-1-phosphate (S1P), a bioactive lipid mediator that regulates many processes in vertebrate development, physiology, and pathology. Once exported out of cells by cell-specific transporters, chaperone-bound S1P is spatially compartmentalized in the circulatory system. Extracellular S1P interacts with five GPCRs that are widely expressed and transduce intracellular signals to regulate cellular behavior, such as migration, adhesion, survival, and proliferation. While many organ systems are affected, S1P signaling is essential for vascular development, neurogenesis, and lymphocyte trafficking. Recently, a pharmacological S1P receptor antagonist has won approval to control autoimmune neuroinflammation in multiple sclerosis. The availability of pharmacological tools as well as mouse genetic models has revealed several physiological actions of S1P and begun to shed light on its pathological roles. The unique mode of signaling of this lysophospholipid mediator is providing novel opportunities for therapeutic intervention, with possibilities to target not only GPCRs but also transporters, metabolic enzymes, and chaperones.


Treatment planning and image guidance for radiofrequency ablation of large tumors.
This article addresses the two key challenges in computer-assisted percutaneous tumor ablation: planning multiple overlapping ablations for large tumors while avoiding critical structures, and executing the prescribed plan. Toward semiautomatic treatment planning for image-guided surgical interventions, we develop a systematic approach to the needle-based ablation placement task, ranging from preoperative planning algorithms to an intraoperative execution platform. The planning system incorporates clinical constraints on ablations and trajectories using a multiple objective optimization formulation, which consists of optimal path selection and ablation coverage optimization based on integer programming. The system implementation is presented and validated in both phantom and animal studies. The presented system can potentially be further extended for other ablation techniques such as cryotherapy.


Optical assays based on colloidal inorganic nanoparticles.
Colloidal inorganic nanoparticles have wide applications in the detection of analytes and in biological assays. A large number of these assays rely on the ability of gold nanoparticles (AuNPs, in the 20 nm diameter size range) to undergo a color change from red to blue upon aggregation. AuNP assays can be based on cross-linking, non-cross linking or unmodified charge-based aggregation. Nucleic acid-based probes, monoclonal antibodies, and molecular-affinity agents can be attached by covalent or non-covalent means. Surface plasmon resonance and SERS techniques can be utilized. Silver NPs also have attractive optical properties (higher extinction coefficient). Combinations of AuNPs and AgNPs in nanocomposites can have additional advantages. Magnetic NPs and ZnO, TiO2 and ZnS as well as insulator NPs including SiO2 can be employed in colorimetric assays, and some can act as peroxidase mimics in catalytic applications. This review covers the synthesis and stabilization of inorganic NPs and their diverse applications in colorimetric and optical assays for analytes related to environmental contamination (metal ions and pesticides), and for early diagnosis and monitoring of diseases, using medically important biomarkers.


Brain atrophy in hypertension. A volumetric magnetic resonance imaging study.
To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean +/- SD age, 69 +/- 8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross-sectional design. Axial proton-density image slices were analyzed using region-of-interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p less than 0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p less than 0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p less than 0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2-weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI-associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction.


[Transcranial magnetic stimulation of the motor cortex and percutaneous magnetic stimulation of the peripheral nervous structures in the dog].
The motor cortex was transcranially and peripheral nervous structures (motor roots, plexus, peripheral nerves) were percutaneously stimulated by magnetic pulses in awake dogs and in dogs awaking from general anesthesia. The compound muscle action potentials were recorded by surface or needle electrodes. The central motor conduction time as an information about central motor tracts was obtained by subtracting the peripheral latency from the corticomuscular latency. The peripheral latency was assessed by high voltage electrical and magnetic stimulation of motor roots and by the F-wave technique. The motor conduction velocity of the tibial nerve was measured by percutaneous magnetic and by electrical stimulation and the resulting values were compared.


Sparse subspace clustering: algorithm, theory, and applications.
Many real-world problems deal with collections of high-dimensional data, such as images, videos, text, and web documents, DNA microarray data, and more. Often, such high-dimensional data lie close to low-dimensional structures corresponding to several classes or categories to which the data belong. In this paper, we propose and study an algorithm, called sparse subspace clustering, to cluster data points that lie in a union of low-dimensional subspaces. The key idea is that, among the infinitely many possible representations of a data point in terms of other points, a sparse representation corresponds to selecting a few points from the same subspace. This motivates solving a sparse optimization program whose solution is used in a spectral clustering framework to infer the clustering of the data into subspaces. Since solving the sparse optimization program is in general NP-hard, we consider a convex relaxation and show that, under appropriate conditions on the arrangement of the subspaces and the distribution of the data, the proposed minimization program succeeds in recovering the desired sparse representations. The proposed algorithm is efficient and can handle data points near the intersections of subspaces. Another key advantage of the proposed algorithm with respect to the state of the art is that it can deal directly with data nuisances, such as noise, sparse outlying entries, and missing entries, by incorporating the model of the data into the sparse optimization program. We demonstrate the effectiveness of the proposed algorithm through experiments on synthetic data as well as the two real-world problems of motion segmentation and face clustering.


Evaluation of computer-based diet education in persons with diabetes mellitus and limited educational background.
A study was conducted to determine whether computer-based techniques for meal planning and diet education could be an effective supplement to diabetes diet counseling in a group of inner-city subjects with limited educational background. Sixteen individuals with diabetes mellitus who were newly referred to an inner-city outpatient diet clinic and who demonstrated ninth-grade reading ability were given computer-based nutritional education. They received meal planning information through use of individualized computer-planned menus and education about the diabetes diet by computer-assisted instruction (CAI) combined with an interactive videodisc system (VIDEO). Total contact time was 180 min of CAI/VIDEO, 50 min of dietitian/patient education, and 20 min of dietitian/patient computer time (the last function could have been performed by a clerk). At the end of 4 wk, the group performance was improved in Exchange Lists knowledge (P less than 0.001), recognition of foods containing concentrated carbohydrate (P less than 0.05), and reduction of reported fat intake (P less than 0.05). In addition, average group weight declined by 4.6 lb (P less than 0.005). No improvement was found in food-measuring skills or in calorie-consumption compliance during a standardized buffet lunch. It appears that computer-based techniques are an acceptable supplement to traditional methods of education in this patient group and can improve the effectiveness of diabetes education programs without a significant increase in dietitian time.


Calorimetric detection of a membrane-lipid phase transition in living cells.
The membrane lipids in living Mycoplasma laidlawii exhibit a phase transition characteristic of that from crystal to liquid crystal within the bilayer conformation. The transition occurs at the same temperature in viable organisms, membranes isolated from the organisms, and isolated membrane lipids. The enthalpy of the transition in the membrane is compared with that of an aqueous suspension of isolated membrane lipids. The result is consistent with presence of an extended lipid bilayer in the native membrane.


Large improvements in MS/MS-based peptide identification rates using a hybrid analysis.
We report a hybrid search method combining database and spectral library searches that allows for a straightforward approach to characterizing the error rates from the combined data. Using these methods, we demonstrate significantly increased sensitivity and specificity in matching peptides to tandem mass spectra. The hybrid search method increased the number of spectra that can be assigned to a peptide in a global proteomics study by 57-147% at an estimated false discovery rate of 5%, with clear room for even greater improvements. The approach combines the general utility of using consensus model spectra typical of database search methods with the accuracy of the intensity information contained in spectral libraries. A common scoring metric based on recent developments linking data analysis and statistical thermodynamics is used, which allows the use of a conservative estimate of error rates for the combined data. We applied this approach to proteomics analysis of Synechococcus sp. PCC 7002, a cyanobacterium that is a model organism for studies of photosynthetic carbon fixation and biofuels development. The increased specificity and sensitivity of this approach allowed us to identify many more peptides involved in the processes important for photoautotrophic growth.


Correlates of HIV acquisition in a cohort of Black men who have sex with men in the United States: HIV prevention trials network (HPTN) 061.
Black men who have sex with men (MSM) in the United States (US) are affected by HIV at disproportionate rates compared to MSM of other race/ethnicities. Current HIV incidence estimates in this group are needed to appropriately target prevention efforts. From July 2009 to October 2010, Black MSM reporting unprotected anal intercourse with a man in the past six months were enrolled and followed for one year in six US cities for a feasibility study of a multi-component intervention to reduce HIV infection. HIV incidence based on HIV seroconversion was calculated as number of events/100 person-years. Multivariate proportional hazards modeling with time-dependent covariates was used to identify correlates of HIV acquisition. Of 1,553 Black MSM enrolled, 1,164 were HIV-uninfected at baseline and included in follow-up. Overall annual HIV incidence was 3.0% (95% confidence interval (CI): 2.0, 4.4%) and 5.9% among men ≤30 years old (95% CI: 3.6, 9.1%). Men ≤30 years old reported significantly higher levels of sexual risk and were more likely to have a sexually transmitted infection diagnosed during follow-up. Younger men also were more likely to not have a usual place for health care, not have visited a health care provider recently, and to have unmet health care needs. In multivariate analysis, age ≤30 years (hazard ratio (HR): 3.4; 95% CI: 1.4, 8.3) and unprotected receptive anal intercourse with HIV-positive or unknown status partners (HR: 4.1; 95% CI: 1.9, 9.1) were significantly associated with HIV acquisition. In the largest cohort of prospectively-followed Black MSM in the US, HIV incidence was high, particularly among young men. Targeted, tailored and culturally appropriate HIV prevention strategies incorporating behavioral, social and biomedical based interventions are urgently needed to lower these rates.


10-year survey of referrals to a pediatric nephrology program.
To provide a realistic picture of the patient case load of a pediatric nephrologist in a teaching hospital, we analyzed the number, the demographics, and the reasons for patient referral to our pediatric nephrology program over a 10-year period. Between January 1, 1978, and December 31, 1987, 1,523 pediatric patients were referred to the Medical College of Virginia for evaluation and treatment of renal and electrolyte disorders. The most common reason for referral was a fluid-electrolyte disorder (30%), followed by hematuria/proteinuria (22%), chronic glomerulonephropathies (10%), hypertension (5%), nephrotic syndrome (6%), end-stage renal disease (3%), urinary tract infections (5%), and acute glomerulonephritis (3%). More than 25% of the patients were under 1 year of age at initial presentation. The rest are equally distributed among the other pediatric age groups, including adolescents. Fifty-eight percent of these patients were white, and 41% were black. Males accounted for 54% of the referrals and females for 46%. Percutaneous renal biopsies were performed under ultrasound guidance on 167 patients or a rate of 17 procedures per year. Fifty-one patients, ranging in age from 0.5 to 19 years, were followed for end-stage renal disease during the 10-year study period. Glomerular disorders accounted for 61% of the end-stage renal diseases and anatomic disorders for 39%. The yearly incidence of end-stage renal diseases over this time was 9.8 patients/million children. Twenty-six (51%) of these patients received one or more kidney transplants during the study period.


Shorter somatic telomere can be an increased risk for hospitalization.
Somatic telomere DNA length is known to shorten with certain disease states and senescence. Furthermore, we have reported that the telomere length of a sub-healthy population also correlates with the blood data of laboratory tests. These facts suggest that patients with shorter telomere length tend to be hospitalized more easily than patients with longer telomere length. And such hospitalization tendencies can also be reflected in differences in clinical laboratory data. To address this issue, we evaluated and compared the telomere length and clinical laboratory data of outpatients and inpatients. In this study, 35 inpatients with chronic illness and 38 outpatients with one or more weeks without hospitalization experience were enrolled. Telomere length was shorter in hospitalized patients than outpatients. Inpatients and outpatients showed significant differences in some laboratory test results. Male outpatients showed higher values of fast blood sugar, HbA1c, blood urea nitrogen, creatinine, C-reactive protein, red blood cell count, and hemoglobin. Among female outpatients, the values of aspartate aminotransferase, alanine aminotransferase, albumin, creatine kinase, red blood cell count and hemoglobin were high. Of these, only albumin levels showed a positive correlation with telomere length in both sexes. Unexpectedly, all the other clinical data distinguishing outpatients and inpatients showed no significant association with telomere length. These items appeared to be related to hospital risk independently of TL. Having a shorter somatic telomere length appeared to be at a higher risk of hospitalization. This risk can be augmented by further complications such as deterioration of nutritional status and anemia. Maintaining sufficiently high nutritional status and erythropoietic potential may lead to avoidance of clinical events that require hospitalization.


Oestrogen replacement therapy may improve memory functioning in the absence of APOE epsilon4.
There is currently intense controversy regarding the use of hormone replacement therapy (HRT) in postmenopausal women, in relation to its therapeutic efficacy in Alzheimer's disease (AD). It has been suggested that the benefits of HRT may be modified by apolipoprotein E (APOE) genotype (the major genetic risk factor for AD). Here we report the findings of the first study designed to systematically explore the interaction of (a) oestrogen replacement therapy (ERT) and (b) possession of an epsilon4 allele of APOE on specific elements of episodic learning and memory that are commonly used indices of age-related cognitive decline. This data represents a cross-sectional analysis of the interaction of ERT and APOE genotype on learning and memory in a cohort of 181 healthy postmenopausal women [ERT users (n = 101, mean age 65.40 +/- 6.34); ERT non-users (n = 80, mean age 67.03 +/- 6.80)] residing in Perth, Western Australia. The highest level of learning (trials 2-5; P < 0.05) and memory (e.g. total number of items recalled; P < 0.05) performance was observed in women taking ERT who were not carriers of the APOE epsilon4 allele. APOEepsilon4 carriers receiving ERT performed no better on episodic memory testing than APOE epsilon4 carriers who were not receiving ERT. These cognitive differences related to genetic profile, were noted on both recall and recognition (P = 0.005) tests of memory. The findings have significance for evaluating whether and when ERT may be clinically indicated. Specifically, ERT may benefit the cognitive functioning of women not carrying the APOE epsilon4 allele.


Impact of the 80-hour workweek on patient care at a level I trauma center.
The 80-hour workweek limitation for surgical residents is associated with an increase in mortality and complication rates among adult trauma surgical patients. Retrospective cohort study. Academic level I trauma center. Trauma patients admitted before and after the 80-hour workweek limitation. We compared death and complication rates for adult trauma patients admitted during a 24-month period before (2001-2003) and a 24-month period after (2004-2006) implementation of the 80-hour workweek at our institution. Relative risk and its 95% confidence intervals were examined. Patient care outcomes included preventable and nonpreventable complications and deaths. The patient populations from the 2 time periods were clinically similar. No significant differences were found in the total and the preventable death rates. The time period after the 80-hour workweek mandate had a significantly higher total complication rate (5.64% vs 7.28%; relative risk, 1.29; 95% confidence interval, 1.15-1.45; P < .001), preventable complication rate (0.89% vs 1.28%; relative risk, 1.43; 95% confidence interval, 1.06-1.91; P = .02), and nonpreventable complication rate (4.75% vs 5.81%; relative risk, 1.22; 95% confidence interval, 1.08-1.39; P = .002). Although there was no difference in deaths between the 2 time periods, there was a significant increase in total, preventable, and nonpreventable complications. This increase in complication rate may be due, in part, to the new 80-hour workweek policy.


Biparietal diameter at 11-13 weeks' gestation in fetuses with open spina bifida.
To ascertain the reported association between reduced biparietal diameter (BPD) at 11-13 weeks' gestation and open spina bifida and to investigate its predictive value in a single-center study. This was a retrospective study of fetuses in which BPD was measured at 11-13 weeks' gestation, including 27 fetuses with isolated open spina bifida subsequently diagnosed at 16-24 weeks and 7775 unaffected controls. BPD values were converted into multiples of the expected median (MoM) after adjustment for crown-rump length and maternal characteristics. Multivariable logistic regression analysis was used to determine the maternal characteristics significantly associated with spina bifida. The performance of screening was determined by receiver-operating characteristics curve analysis. BPD values at 11-13 weeks' gestation were compared with those measured in the second trimester using Z-scores. BPD values at 11-13 weeks' gestation were below the 5(th) centile in 44.4% of cases of open spina bifida. In these fetuses, the median BPD MoM value was significantly smaller than that in the control group (0.930 vs 0.998 MoM; P < 0.0001). Multivariable logistic regression analysis showed a significant contribution from maternal age (P = 0.008) and BMI (P = 0.028) to the association between BPD MoM and spina bifida. The detection rate using BPD measurements in the first trimester was 55.6% with a false-positive rate of 11.6%. In fetuses with open spina bifida, the BPD Z-scores were significantly lower at 16-24 weeks compared to those recorded at 11-13 weeks (median, -1.71 (range, -3.98 to -0.20) vs -1.30 (-3.75 to 2.61); P = 0.006). Fetuses with open spina bifida have a smaller BPD in the first trimester. This observation may be useful in early screening. It is likely that a combination of maternal characteristics such as age and BMI, fetal BPD and maternal serum alpha-fetoprotein measured in the first trimester would provide a clinically useful screening test for open spina bifida.


Risk-adjusted cUSUM control charts for shared frailty survival models with application to hip replacement outcomes: a study using the NJR dataset.
Continuous monitoring of surgical outcomes after joint replacement is needed to detect which brands' components have a higher than expected failure rate and are therefore no longer recommended to be used in surgical practice. We developed a monitoring method based on cumulative sum (CUSUM) chart specifically for this application. Our method entails the use of the competing risks model with the Weibull and the Gompertz hazard functions adjusted for observed covariates to approximate the baseline time-to-revision and time-to-death distributions, respectively. The correlated shared frailty terms for competing risks, corresponding to the operating unit, are also included in the model. A bootstrap-based boundary adjustment is then required for risk-adjusted CUSUM charts to guarantee a given probability of the false alarm rates. We propose a method to evaluate the CUSUM scores and the adjusted boundary for a survival model with the shared frailty terms. We also introduce a unit performance quality score based on the posterior frailty distribution. This method is illustrated using the 2003-2012 hip replacement data from the UK National Joint Registry (NJR). We found that the best model included the shared frailty for revision but not for death. This means that the competing risks of revision and death are independent in NJR data. Our method was superior to the standard NJR methodology. For one of the two monitored components, it produced alarms four years before the increased failure rate came to the attention of the UK regulatory authorities. The hazard ratios of revision across the units varied from 0.38 to 2.28. An earlier detection of failure signal by our method in comparison to the standard method used by the NJR may be explained by proper risk-adjustment and the ability to accommodate time-dependent hazards. The continuous monitoring of hip replacement outcomes should include risk adjustment at both the individual and unit level.


Nursing students administering medication: appreciating and seeking appropriate supervision.
This paper is a report of a study of undergraduate nursing students' experience of administering medication in the clinical setting. Safe administration of medication is an important component of skilled nursing practice, and nursing students require personal and supportive supervision from Registered Nurses to enhance learning and promote safety. A review of the literature revealed a lack of research addressing students' experiences in administering medication. A grounded theory methodology was used. In-depth semi-structured interviews were conducted with a convenience sample of 27 undergraduate nursing students in Queensland Australia in 2005. Supervision emerged as the central category in this study. Participants acknowledged the need for and importance of supervision according to the following sub-themes: a university requirement; scope of practice; and safety, the five rights. They also described behaviours they adopted to seek supervision, including negotiating, chasing, waiting and avoiding. Universities and healthcare settings need to collaborate more closely to ensure that adequate supervision is provided to ensure safe practices.


A predictive model for mortality in massively transfused trauma patients.
Improvements in trauma systems and resuscitation have increased survival in severely injured patients. Massive transfusion has been increasingly used in the civilian setting. Objective predictors of mortality have not been well described. This study examined data available in the early postinjury period to identify variables that are predictive of 24-hour- and 30-day mortality in massively transfused trauma patients. Massively transfused trauma patients from 23 Level I centers were studied. Variables available on patient arrival that were predictive of mortality at 24 hours were entered into a logistic regression model. A second model was created adding data available 6 hours after injury. A third model evaluated mortality at 30 days. Receiver operating characteristic curves and the Hosmer-Lemeshow test were used to assess model quality. Seven hundred four massively transfused patients were analyzed. The model best able to predict 24-hour mortality included pH, Glasgow Coma Scale score, and heart rate, with an area under the receiver operating characteristic curve (AUROC) of 0.747. Addition of the 6-hour red blood cell requirement increased the AUROC to 0.769. The model best able to predict 30-day mortality included the above variables plus age and Injury Severity Score with an AUROC of 0.828. Glasgow Coma Scale score, pH, heart rate, age, Injury Severity Score, and 6-hour red blood cell transfusion requirement independently predict mortality in massively transfused trauma patients. Models incorporating these data have only a modest ability to predict mortality and should not be used to justify withholding massive transfusion in individual cases.


Collection and characterisation of bacterial membrane proteins.
A general strategy for the amplified expression in Escherichia coli of membrane transport and receptor proteins from other bacteria is described. As an illustration we report the cloning of the putative alpha-ketoglutarate membrane transport gene from the genome of Helicobacter pylori, overexpression of the protein tagged with RGS(His)6 at the C-terminus, and its purification in mg quantities. The retention of structural and functional integrity was verified by circular dichroism spectroscopy and reconstitution of transport activity. This strategy for overexpression and purification is extended to additional membrane proteins from H. pylori and from other bacteria.


A structural study of the interaction between the Dr haemagglutinin DraE and derivatives of chloramphenicol.
Dr adhesins are expressed on the surface of uropathogenic and diffusely adherent strains of Escherichia coli. The major adhesin subunit (DraE/AfaE) of these organelles mediates attachment of the bacterium to the surface of the host cell and possibly intracellular invasion through its recognition of the complement regulator decay-accelerating factor (DAF) and/or members of the carcinoembryonic antigen (CEA) family. The adhesin subunit of the Dr haemagglutinin, a Dr-family member, additionally binds type IV collagen and is inhibited in all its receptor interactions by the antibiotic chloramphenicol (CLM). In this study, previous structural work is built upon by reporting the X-ray structures of DraE bound to two chloramphenicol derivatives: chloramphenicol succinate (CLS) and bromamphenicol (BRM). The CLS structure demonstrates that acylation of the 3-hydroxyl group of CLM with succinyl does not significantly perturb the mode of binding, while the BRM structure implies that the binding pocket is able to accommodate bulkier substituents on the N-acyl group. It is concluded that modifications of the 3-hydroxyl group would generate a potent Dr haemagglutinin inhibitor that would not cause the toxic side effects that are associated with the normal bacteriostatic activity of CLM.


The effect of fluid shear stress upon cell adhesion to fibronectin-treated surfaces.
Cell attachment to and spreading upon a surface is mediated by adhesion molecules, such as fibronectin. The role of fibronectin in maintaining cell adhesion was examined by measuring cell attachment following exposure of cells to laminar flow in a parallel-plate flow channel. 3T3 fibroblasts were allowed to adhere to glass slides with or without preadsorbed fibronectin for 2 h before exposure to shear stresses ranging from 5 to 140 dyne/cm2. For cells which adhered to glass surfaces, cell loss was biphasic with a significant loss of cells during the first 2 min of flow, followed by a much slower decline in the number of attached cells with time. Following exposure to shear stresses greater than 5 dyne/cm2, the number of attached cells decreased exponentially as the shear stress increased. The distribution of adhesive stresses among the population of cells was log-normal with a median of 50 dyne/cm2, a mean of 82 dyne/cm2 and a standard deviation of 108 dyne/cm2. After exposure to flow for 2 h, the adhesive stress of the remaining cells decreased to a mean value of 50 dyne/cm2. Cell adhesion after exposure to flow was increased by preadsorbing fibronectin to the glass surface. The initial loss of cells from fibronectin-treated glass following exposure to flow correlated with the degree of cell spreading. Preadsorbed fibronectin resulted in a greater number of bonds between the surface and the cell, which in turn promoted cell spreading and increased the adhesive strength of the cell.


Proteome and transcriptome analysis of cell death induced by 5-fluoro-2'-deoxyuridine.
5-fluoro-2'-deoxyuridine (FUdR) inhibits thymidylate synthase. We have been investigated the molecular mechanisms of cell death in mouse mammary tumor FM3A cells, F28-7 strain and its mutant F28-7-A strain, after treated with FUdR. Previously, we have been reported that F28-7 strain induced DNA cleavage into chromosomal sized fragments and subsequently develop necrosis, but F28-7-A strain induced DNA cleavage into oligonucleosomal sized fragments and subsequently develop apoptosis after treated with FUdR. To understand the molecular mechanisms of regulate of two differential cell death necrosis and apoptosis, we identify cell death regulator by using proteome and transcriptome analysis. When compared with the proteome of F28-7 and F28-7-A strain after treated with FUdR, it was found that 5 proteins were up-regulated and 11 proteins were down-regulated in F28-7-A strain. Furthermore, transcriptome analysis shows that 94 genes were up-regulated and 164 genes were downregulated in F28-7-A strain. Identified proteins and genes were involved in various cellular processes such as cell cycle regulation, apoptosis, proliferation, and differentiation. Our results suggested that numerous features indicated the coordinated regulation of molecular networks from various aspects of necrosis or apoptosis at the proteome and transcriptome levels.


[Anisakiasis in a patient with a small hiatal hernia. Report of one case].
We describe the presence of anisakiasis in a patient who had a small hiatal hernia. A 60 year-old women presented general malaise, burning pain, flatulence, persistent nausea and abdominal distension during five days before consulting. She referred that she ate a dish of marinated raw fish with lemon and pepper ("cebiche") and after a few hours the symptoms began. An esophagogastroscopy showed a white colour larva of approximately three cm with the cephalic end partially adhered and localized in the mucosa of the hiatal hernia. During the procedure the worm was easily extracted. The morphologic study of the specimen identified it as a stage IV larva of Pseudoterranova sp. The clinical condition of the patient improved after the extraction of the parasite.


Health-care reforms in the People's Republic of China--strategies and social implications.
Analyses the features, strategies and characteristics of health-care reforms in the People's Republic of China. Since the 14th Central Committee of the Chinese Communist Party held in 1992, an emphasis has been placed on reform strategies such as cost recovery, profit making, diversification of services, and development of alternative financing strategies in respect of health-care services provided in the public sector. Argues that the reform strategies employed have created new problems before solving the old ones. Inflation of medical cost has been elevated very rapidly. The de-linkage of state finance bureau and health service providers has also contributed to the transfer of tension from the state to the enterprises. There is no sign that quasi-public health-care insurance is able to resolve these problems. Finally, cooperative medicine in the rural areas has been largely dismantled, though this direction is going against the will of the state. Argues that a new balance of responsibility has to be developed as a top social priority between the state, enterprises and service users in China in order to meet the health-care needs of the people.


Immigrants Equilibrate Local Labor Markets: Evidence from the Great Recession.
This paper demonstrates that low-skilled Mexican-born immigrants' location choices in the U.S. respond strongly to changes in local labor demand, and that this geographic elasticity helps equalize spatial differences in labor market outcomes for low-skilled native workers, who are much less responsive. We leverage the substantial geographic variation in employment losses that occurred during Great Recession, and our results confirm the standard finding that high-skilled populations are quite geographically responsive to employment opportunities while low-skilled populations are much less so. However, low-skilled immigrants, especially those from Mexico, respond even more strongly than high-skilled native-born workers. Moreover, we show that natives living in metro areas with a substantial Mexican-born population are insulated from the effects of local labor demand shocks compared to those in places with few Mexicans. The reallocation of the Mexican-born workforce reduced the incidence of local demand shocks on low-skilled natives' employment outcomes by more than 50 percent.


Modulus-density scaling behaviour and framework architecture of nanoporous self-assembled silicas.
Natural porous materials such as bone, wood and pith evolved to maximize modulus for a given density. For these three-dimensional cellular solids, modulus scales quadratically with relative density. But can nanostructuring improve on Nature's designs? Here, we report modulus-density scaling relationships for cubic (C), hexagonal (H) and worm-like disordered (D) nanoporous silicas prepared by surfactant-directed self-assembly. Over the relative density range, 0.5 to 0.65, Young's modulus scales as (density)n where n(C)<n(H)<n(D)<2, indicating that nanostructured porous silicas exhibit a structure-specific hierarchy of modulus values D<H<C. Scaling exponents less than 2 emphasize that the moduli are less sensitive to porosity than those of natural cellular solids, which possess extremal moduli based on linear elasticity theory. Using molecular modelling and Raman and NMR spectroscopy, we show that uniform nanoscale confinement causes the silica framework of self-assembled silica to contain a higher portion of small, stiff rings than found in other forms of amorphous silica. The nanostructure-specific hierarchy and systematic increase in framework modulus we observe, when decreasing the silica framework thickness below 2 nm, provides a new ability to maximize mechanical properties at a given density needed for nanoporous materials integration.


Pester power and its consequences: do European children's food purchasing requests relate to diet and weight outcomes?
Children may influence household spending through 'pester power'. The present study examined pestering through parent-child food shopping behaviours in relation to children's diet and weight status. Cross-sectional and prospective analyses drawn from the IDEFICS study, a cohort study of parents and their children. Children's height and weight were measured and their recent diets were reported by parental proxy based on the Children's Eating Habits Questionnaire-FFQ at baseline and 2-year follow-up. Parents also completed questionnaires at both time points about pestering, including whether the child goes grocery shopping with them, asks for items seen on television and is bought requested food items. Participants were recruited from eight European countries for the IDEFICS study (non-nationally representative sample). Study participants were children aged 2-9 years at enrolment and their parents. A total of 13 217 parent-child dyads were included at baseline. Two years later, 7820 of the children were re-examined. Most parents (63 %) at baseline reported 'sometimes' acquiescing to their children's requests to purchase specific foods. Pestering was modestly associated with weight and diet. At baseline, children whose parents 'often' complied consumed more high-sugar and high-fat foods. Children who 'often' asked for items seen on television were likely to become overweight after 2 years (OR=1·31), whereas 'never' asking protected against overweight (OR=0·72). Pestering was modestly related to diet and weight in cross-sectional, but not longitudinal analyses. Asking for items seen on television had the most robust relationships across child outcomes and over time.


Anxiety responses to maximal exercise testing.
The influence of maximal exercise testing on state anxiety was examined in three separate studies. Highly trained male distance runners (Study 1, n = 12) as well as college students with average (Study 2, n = 16) and below average (Study 3, n = 32) physical fitness levels completed graded maximal exercise tests. This last group was also randomly assigned to either a control or an 8 week training programme in order to determine the effect of increased fitness on the psychological responses to maximal exercise testing. Physical fitness was determined by the measurement of maximal oxygen uptake. State anxiety (State-Trait Anxiety Inventory) was assessed before and from 2-15 min following exercise. It was found that the state anxiety responses to maximal exercise testing were not influenced by re-testing or by 8 weeks of endurance training. Across the three study groups, the anxiety response was variable during the first 5 min following exercise testing; increases, decreases and no changes in anxiety were observed when compared to pre-exercise levels. The anxiety response to maximal exercise appeared to be dependent on the pre-exercise anxiety levels as well as the timing of the post-exercise assessments. It is concluded that maximal exercise testing can be associated with negative mood shifts during the first 5 min after exercise; however, this response is transitory and followed by positive mood shifts 10-15 min following such tests.


Skin Tone Matters: Racial Microaggressions and Delayed Prenatal Care.
Literature posits that discrimination can be a barrier to racial and ethnic minorities' healthcare use. This study examines the relationship between perceived discrimination in the form of racial microaggressions and delayed prenatal care in African American women. It also investigates whether this relationship is modified by women's shade of skin color owing to societal attitudes and beliefs tied to colorism (also known as skin-tone bias). Data were collected from a cohort of 1,410 black, African American women in metropolitan Detroit, Michigan, enrolled in 2009-2011 (analyzed between August 2017 and July 2018). Perceived racial microaggressions were assessed using the 20-item Daily Life Experiences of Racism and Bother scale. Logistic regression modeled the relationship between the Daily Life Experiences of Racism and Bother scale and delayed prenatal care, defined as third trimester or no prenatal care entry. Nearly a quarter (24.8%) of women had delayed prenatal care. Logistic regression models showed that a Daily Life Experiences of Racism and Bother score above the median was associated with delayed prenatal care (AOR=1.31, 95% CI=1.00, 1.71). This association was moderated by self-reported maternal skin tone (interaction p=0.03). A higher Daily Life Experiences of Racism and Bother score was associated with delayed prenatal care among African-American women at either end of the color continuum (light brown: AOR=1.64, 95% CI=1.02, 2.65; dark brown: AOR=2.30, 95% CI=1.20, 4.41) but not in the middle (medium brown women). Skin tone-based mistreatment in tandem with racial discrimination in the form of racial microaggressions may influence African American women's use of prenatal care. These findings have implications related to the engagement of women of color, particularly African American women, in healthcare systems and maternal and child health programs.


Martensitic transformation of FeNi nanofilm induced by interfacial stress generated in FeNi/V nanomultilayered structure.
FeNi/V nanomultilayered films with different V layer thicknesses were synthesized by magnetron sputtering. By adjusting the thickness of the V layer, different interfacial compressive stress were imposed on FeNi layers and the effect of interfacial stress on martensitic transformation of the FeNi film was investigated. Without insertion of V layers, the FeNi film exhibits a face-centered cubic (fcc) structure. With the thickness of V inserted layers up to 1.5 nm, under the coherent growth structure in FeNi/V nanomultilayered films, FeNi layers bear interfacial compressive stress due to the larger lattice parameter relative to V, which induces the martensitic transformation of the FeNi film. As the V layer thickness increases to 2.0 nm, V layers cannot keep the coherent growth structure with FeNi layers, leading to the disappearance of interfacial compressive stress and termination of the martensitic transformation in the FeNi film. The interfacial compressive stress-induced martensitic transformation of the FeNi nanofilm is verified through experiment. The method of imposing and modulating the interfacial stress through the epitaxial growth structure in the nanomultilayered films should be noticed and utilized.


Gender-specific trends in the value of education and the emerging gender gap in college completion.
Analysis of March Current Population Survey data from 1964 through 2002 shows that white women overtook white men in their rates of college completion and that this phenomenon occurred during a period in which women's standard-of-living gains from college completion grew at a faster rate than those for men. We assess whether these trends are related to changes in the value of education for men and women in terms of earnings returns to higher education, the probability of getting and staying married, education-related differences in family standard of living, and insurance against living in poverty. Although returns to a college education in the form of earnings remained higher for women than for men over the entire period, trends in these returns do not provide a plausible explanation for gender-specific trends in college completion. But when broader measures of material well-being are taken into account, women's returns to higher education appear to have risen faster than those of men.


Malaria infection at parturition in Abeokuta, Nigeria: Current status and pregnancy outcome.
There is dearth of information on perinatally acquired malaria, as well as its burden in Nigeria. We determined the prevalence of pregnancy-associated malaria and its burden among parturients in Abeokuta, Ogun State. Blood films from 211 parturients were prepared, stained with 10% Giemsa and examined using microscopy. Relevant demographic information was recorded from study participants. Chi-square tests were used to analyse data using SPSS version 20.0. Prevalence of maternal peripheral, placenta and cord blood parasitaemia were 40.8%, 19.0% and 5.7% respectively, and these were significantly correlated with age and gravidity. Prevalence of maternal anaemia was 45.0%, and was significantly associated with malaria infection. The occurrence of Low Birth Weight (LBW) was 10%. Maternal, placental and cord infections with malaria were associated with LBW, with the highest percentage of LBW occurring in babies with high placental malaria parasite density. Preterm delivery and stillbirth were significantly associated with placenta and cord malaria. Impact of malaria on the mother and the newborns, notably anaemia and LBW, solicits the need for promoting use of available malaria prevention during pregnancy. These include LLINs and IPTp.


Preoperative Hemoglobin Level is Associated with Increased Health Care Use After Elective Spinal Fusion (≥3 Levels) in Elderly Male Patients with Spine Deformity.
Measures of health care use such as length of hospital stay (LOS) are used as proxies for quality of care after spine surgery. Accordingly, hospitals and health systems are investing considerable resources into the preoperative identification of patients at risk for prolonged LOS. This study aims to investigate the impact of preoperative level on outcomes and LOS after spinal fusion. The medical records of 204 elderly (≥60 years) male patients undergoing elective spinal fusion (≥3 levels) at a major academic institution from 2005 to 2015 were reviewed. The lower hemoglobin (Hgb) level was designated as <13.5 g/dL. We identified 83 (40.7%) patients with preoperative lower Hgb levels and 121 (59.3%) with normal levels (low Hgb, n = 83; normal Hgb, n = 121). The primary outcomes investigated were complications and LOS. Demographics and comorbidities were similar between both groups, with mean Hgb levels being 12.3 ± 0.9 g/dL and 14.9 ± 1.0 g/dL for the low and normal cohorts, respectively. The lower Hgb cohort experienced higher rates of postoperative delirium (21.7% vs. 5.8%; P = 0.0007), non-wound infections (6.0% vs. 0.0%; P = 0.006), and hematoma formation (3.6% vs. 0.0%; P = 0.035). There was a significant difference in LOS between the cohorts, with the low Hgb cohort experiencing approximately a 2-fold increase (low Hgb, 8.1 ± 5.9 days vs. normal Hgb, 4.8 ± 2.5 days; P < 0.0001). Preoperative Hgb and hematocrit levels negatively correlated with LOS (Hgb, R = -0.388, P < 0.001 and Hct, R = -0.2883, P < 0.001). Our study shows that elderly male patients with lower preoperative Hgb levels have increased LOS and postoperative delirium after spinal fusion. Moreover, preoperative Hgb levels negatively correlate with LOS.


Non-convex Learning via Replica Exchange Stochastic Gradient MCMC.
Replica exchange Monte Carlo (reMC), also known as parallel tempering, is an important technique for accelerating the convergence of the conventional Markov Chain Monte Carlo (MCMC) algorithms. However, such a method requires the evaluation of the energy function based on the full dataset and is not scalable to big data. The naïve implementation of reMC in mini-batch settings introduces large biases, which cannot be directly extended to the stochastic gradient MCMC (SGMCMC), the standard sampling method for simulating from deep neural networks (DNNs). In this paper, we propose an adaptive replica exchange SGMCMC (reSGMCMC) to automatically correct the bias and study the corresponding properties. The analysis implies an acceleration-accuracy trade-off in the numerical discretization of a Markov jump process in a stochastic environment. Empirically, we test the algorithm through extensive experiments on various setups and obtain the state-of-the-art results on CIFAR10, CIFAR100, and SVHN in both supervised learning and semi-supervised learning tasks.


Patient Participation and the Use of Ehealth Tools for Pharmacoviligance.
In recent years, pharmacovigilance has undergone some major changes. First, the patient's active role in identifying and describing adverse drug reactions (ADRs) has gained recognition. Second, pharmacovigilance has increasingly incorporated information and communications technology (ICT). Patients can now upload their own reports of ADRs online. Data on intensive medication monitoring are now collected via the Internet and smartphones. Worldwide collection of AEs using smart phones might become the leading technique in Low and Middle Income Countries where broad mobile phone service can be managed cheaper than Internet communication. At the same time, researchers are exploring the potential for data sharing via online forums and Internet search engines. In particular we synthetize the Pros and cons of the various methods for gathering pharmacovigilance data (i.e., Web-based spontaneous reporting of adverse drug reactions; Intensive drug monitoring studies; Analysis of online forum postings; Use of mobile phone systems to monitor drug effects). This article describes these advances and highlights their respective contributions.


Lipophilic 4-isoxazolyl-1,4-dihydropyridines: synthesis and structure-activity relationships.
A series of 4-isoxazolyl-1,4-dihydropyridines bearing lipophilic side chains at the C-5 position of the isoxazole ring have been prepared. The calcium channel antagonistic activity of these compounds has been evaluated. A hypothetical model for binding of these compounds in the calcium channel is proposed, and the validity of this model is evaluated based on the SAR of this series of calcium binding, especially for the two most active derivatives, 1a, g. The solid-state structure for the most active compound, 1a, has also been determined, and its important features are reported.


Effectiveness of Family Integrated Care in neonatal intensive care units on infant and parent outcomes: a multicentre, multinational, cluster-randomised controlled trial.
Despite evidence suggesting that parent involvement was beneficial for infant and parent outcomes, the Family Integrated Care (FICare) programme was one of the first pragmatic approaches to enable parents to become primary caregivers in the neonatal intensive care unit (NICU). We aimed to analyse the effect of FICare on infant and parent outcomes, safety, and resource use. In this multicentre, cluster-randomised controlled trial, we stratified 26 tertiary NICUs from Canada, Australia, and New Zealand by country and size, and assigned them, using a computer-generated random allocation sequence, to provide FICare or standard NICU care. Eligible infants were born at 33 weeks' gestation or earlier, and had no or low-level respiratory support; parents gave written informed consent for enrolment. To be eligible, parents in the FICare group had to commit to be present for at least 6 h a day, attend educational sessions, and actively care for their infant. The primary outcome, analysed at the individual level, was infant weight gain at day 21 after enrolment. Secondary outcomes were weight gain velocity, high frequency breastfeeding (≥6 times a day) at hospital discharge, parental stress and anxiety at enrolment and day 21, NICU mortality and major neonatal morbidities, safety, and resource use (including duration of oxygen therapy and hospital stay). This trial is registered with ClinicalTrials.gov, number NCT01852695. From Oct 1, 2012, 26 sites were randomly assigned to provide FICare (n=14) or standard care (n=12). One site assigned to FICare discontinued because of poor site enrolment. Parents and infants were enrolled between April 1, 2013, and Aug 31, 2015, with 895 infants being eligible in the FICare group and 891 in the standard care group. At day 21, weight gain was greater in the FICare group than in the standard care group (mean change in Z scores -0·071 [SD 0·42] vs -0·155 [0·42]; p<0·0002). Average daily weight gain was significantly higher in infants receiving FICare than those receiving standard care (mean daily weight gain 26·7 g [SD 9·4] vs 24·8 g [9·5]; p<0·0001). The high-frequency exclusive breastmilk feeding rate at discharge was higher for infants in the FICare group (279 [70%] of 396) than those in the standard care group (394 [63%] of 624; p=0·016). At day 21, parents in the FICare group had lower mean stress scores than did parents in the standard care group (2·3 [SD 0·8] vs 2·5 [0·8]; p<0·00043), and lower mean anxiety scores (70·8 [20·1] vs 74·2 [19·9]; p=0·0045). There were no significant differences between groups in the rates of the secondary outcomes of mortality, major morbidity, duration of oxygen therapy, and duration of hospital stay. Although the safety assessment was not completed, there were no adverse events. FICare improved infant weight gain, decreased parent stress and anxiety, and increased high-frequency exclusive breastmilk feeding at discharge, which together suggest that FICare is an important advancement in neonatal care. Further research is required to examine if these results translate into better long-term outcomes for families. Canadian Institutes of Health Research Partnerships for Health System Improvement, and Ontario Ministry of Health and Long-Term Care.


Imaging retrobulbar subarachnoid space around optic nerve by swept-source optical coherence tomography in eyes with pathologic myopia.
To examine the subarachnoid space (SAS) of eyes with pathologic myopia and analyze the characteristics of the SAS and the surrounding tissues by swept-source optical coherence tomography (OCT). One hundred thirty-three eyes of 76 patients with pathologic myopia (spherical equivalent refractive error of >-8.00 diopters (D) or an axial length >26.5 mm) and 32 eyes of 32 subjects with emmetropia were enrolled. The eyes in both groups were not tested to determine whether glaucoma was present. The papillary and peripapillary areas were examined with a swept-source OCT prototype system that uses a wavelength sweeping laser operated at 100,000 Hz A-scan repetition rate in 1-μm wavelength. In the B-scan images, the arachnoid trabeculae inside the SAS were clearly observed as a pattern of reticular lines and dots interspersed with hyporeflective zones consistent with fluid, whereas orbital fat had more uniform features with gray intervening spaces. The SAS was triangular, with the base toward the eye surrounding the optic nerve in the region of the scleral flange. An SAS was found in 124 highly myopic eyes (93.2%) but not in the emmetropic eyes. The shortest distance between the inner surface of lamina cribrosa and SAS was 252.4 ± 110.9 μm, and the thinnest region of peripapillary sclera above SAS (scleral flange thickness) was 190.6 ± 51.2 μm. In one myopic patient, there appeared to be direct communication between the intraocular cavity and SAS through pitlike pores. Optic SAS is seen in 93% of highly myopic eyes, and the SAS appears to be dilated in highly myopic eyes. The expanded area of exposure to CSF pressure along with thinning of the posterior eye wall may influence staphyloma formation and the way in which certain diseases, such as glaucoma, are manifested.


Intragenic suppression of integration-defective IS10 transposase mutants.
IS10 transposase mediates excision and integration reactions in Tn10/IS10 transposition. Mutations in IS10 transposase that specifically block integration have previously been identified; however, the mechanism by which these mutations block integration has not been established. One approach to defining the basis of this block is to identify ways in which the original defect can be corrected. The approach we have taken toward this end has been to isolate and characterize intragenic second site suppressors to two different integration-defective mutants. Of the second site suppressors identified, one, CY134, is of particular interest for two reasons. First, it suppresses at least seven different mutations that confer an integration-defective phenotype. Interestingly, these mutations map in two separate segments of transposase, designated patch I and patch II. Second, CY134 on its own has previously been shown to relax the target DNA sequence requirements for Tn10 integration. We provide evidence that suppression by CY134 is not simply a consequence of this mutation conferring a general "transposition up" phenotype, but rather is due to correcting the original defect. Possible mechanisms of suppression for both CY134 and other second site suppressors are considered.


New parasites and predators follow the introduction of two fish species to a subarctic lake: implications for food-web structure and functioning.
Introduced species can alter the topology of food webs. For instance, an introduction can aid the arrival of free-living consumers using the new species as a resource, while new parasites may also arrive with the introduced species. Food-web responses to species additions can thus be far more complex than anticipated. In a subarctic pelagic food web with free-living and parasitic species, two fish species (arctic charr Salvelinus alpinus and three-spined stickleback Gasterosteus aculeatus) have known histories as deliberate introductions. The effects of these introductions on the food web were explored by comparing the current pelagic web with a heuristic reconstruction of the pre-introduction web. Extinctions caused by these introductions could not be evaluated by this approach. The introduced fish species have become important hubs in the trophic network, interacting with numerous parasites, predators and prey. In particular, five parasite species and four predatory bird species depend on the two introduced species as obligate trophic resources in the pelagic web and could therefore not have been present in the pre-introduction network. The presence of the two introduced fish species and the arrival of their associated parasites and predators increased biodiversity, mean trophic level, linkage density, and nestedness; altering both the network structure and functioning of the pelagic web. Parasites, in particular trophically transmitted species, had a prominent role in the network alterations that followed the introductions.


Trans-suppression of misfolding in an amyloid disease.
The transthyretin (TTR) amyloid diseases, representative of numerous misfolding disorders, are of considerable interest because there are mutations that cause or suppress disease. The Val30 --> Met30 (V30M) TTR mutation is the most prevalent cause of familial amyloid polyneuropathy in heterozygotes, whereas a Thr119 --> Met119 (T119M) mutation on the second TTR allele protects V30M carriers from disease. Here, we show that the incorporation of one or more T119M TTR subunits into a predominantly V30M tetramer strongly stabilized the mixed tetramer against dissociation. Dissociation is required for amyloid formation, so these findings provide a molecular explanation for intragenic trans-suppression of amyloidosis. The data also suggest a potential therapeutic strategy, provide insight into tissue-specific deposition and amyloid composition, and support the validity of the amyloid hypothesis in human disease.


Data Collection as Disruption: Insights from a Longitudinal Study of Young Adulthood.
Research disrupts the social world, often by making respondents aware that they are being observed or by instigating reflection upon particular aspects of life via the very act of asking questions. Building on insights from the first Hawthorne studies, reflexive ethnographers, and methodologists concerned with panel conditioning, we draw on six years of research within a community in southern Malawi to introduce a conceptual framework for theorizing disruption in observational research. We present a series of poignant-yet-typical tales from the field and two additional tools-the refresher-sample-as-comparison and study-focused ethnography-for measuring disruption empirically in a longitudinal study. We find evidence of study effects in many domains of life that relate directly to our scope of inquiry (i.e., union formation, fertility) and in some that extend beyond it (i.e., health). Moreover, some study effects were already known and discussed in the broader community, which was also affected by our research in unintended ways. We conclude that the assumption of non-interactivity in observational research is shaky at best, urging data-gatherers and users to think more seriously about the role of disruption in their work.


Capture, release and culture of circulating tumor cells from pancreatic cancer patients using an enhanced mixing chip.
Circulating tumor cells (CTCs) from peripheral blood hold important information for cancer diagnosis and disease monitoring. Analysis of this "liquid biopsy" holds the promise to usher in a new era of personalized therapeutic treatments and real-time monitoring for cancer patients. But the extreme rarity of CTCs in blood makes their isolation and characterization technologically challenging. This paper reports the development of a geometrically enhanced mixing (GEM) chip for high-efficiency and high-purity tumor cell capture. We also successfully demonstrated the release and culture of the captured tumor cells, as well as the isolation of CTCs from cancer patients. The high-performance microchip is based on geometrically optimized micromixer structures, which enhance the transverse flow and flow folding, maximizing the interaction between CTCs and antibody-coated surfaces. With the optimized channel geometry and flow rate, the capture efficiency reached >90% with a purity of >84% when capturing spiked tumor cells in buffer. The system was further validated by isolating a wide range of spiked tumor cells (50-50,000) in 1 mL of lysed blood and whole blood. With the combination of trypsinization and high flow rate washing, captured tumor cells were efficiently released. The released cells were viable and able to proliferate, and showed no difference compared with intact cells that were not subjected to the capture and release process. Furthermore, we applied the device for detecting CTCs from metastatic pancreatic cancer patients' blood; and CTCs were found from 17 out of 18 samples (>94%). We also tested the potential utility of the device in monitoring the response to anti-cancer drug treatment in pancreatic cancer patients, and the CTC numbers correlated with the clinical computed tomograms (CT scans) of tumors. The presented technology shows great promise for accurate CTC enumeration, biological studies of CTCs and cancer metastasis, as well as for cancer diagnosis and treatment monitoring.