Minimally invasive lateral lumbar interbody fusion and transpsoas approach-related morbidity.
Recently, the minimally invasive, lateral retroperitoneal, transpsoas approach to the thoracolumbar spinal column has been described by various authors. This is known as the minimally invasive lateral lumbar interbody fusion. The purpose of this study is to elucidate the approach-related morbidity associated with the minimally invasive transpsoas approach to the lumbar spine. To date, there have been only a couple of reports regarding the morbidity of the transpsoas muscle approach. A nonrandomized, prospective study utilizing a self-reported patient questionnaire was conducted between January 2006 and June 2008 at Northwestern University. Data were collected in 53 patients with a follow-up period ranging from 6 months to 3.5 years. Only 2 patients were lost to follow-up. Thirty-six percent (19 of 53) of patients reported subjective hip flexor weakness, 25% (13 of 53) anterior thigh numbness, and 23% (12 of 53) anterior thigh pain. However, 84% of the 19 patients reported complete resolution of their subjective hip flexor weakness by 6 months, and most experienced improved strength by 8 weeks. Of those reporting anterior thigh numbness and pain, 69% and 75% improved to their baseline function by the 6-month follow-up evaluations, respectively. All patients with self-reported subjective hip flexor weakness underwent examinations during subsequent clinic visits after surgery; however, these examinations did not confirm a motor deficit less than Grade 5. Subset analysis showed that the L3-4 and L4-5 levels were most often affected. The minimally invasive, transpsoas muscle approach to the lumbar spine has a number of advantages. The data show that a percentage of the patients undergoing the transpsoas approach will have temporary sensory and motor symptoms related to this approach. The majority of the symptoms are thought to be related to psoas muscle inflammation and/or stretch injury to the genitofemoral nerve due to the surgical corridor traversed during the operation. No major injuries to the lumbar plexus were encountered. It is important to educate patients prior to surgery of the possibility of these largely transient symptoms.


Exploring the potential impacts of tourism development on social and ecological change in the Solomon Islands.
Pacific Island communities may be vulnerable to negative impacts of economic development, which is often considered a strategy for reducing vulnerability to environmental change. Studies that evaluate potential impacts of economic development in isolated communities may be inaccurate to only focus on asking people to anticipate impacts of phenomena they have had minimal exposure to. We used an open-ended approach to evaluate how communities in the Solomon Islands perceived change, and used this information to anticipate potential impacts of the government's plans to develop tourism. Our results showed mostly negative expectations of change, particularly socio-cultural, which was perceived as being driven by diminishing social capital, foreign influence, and economic development. Despite minimal exposure, locals supported tourism and had more positive expectations of change associated with this activity. Our findings emphasize the need for locally appropriate planning to ensure intended positive impacts of tourism and other forms of economic development.


Therapeutic immunosuppression of T cells.
Current immunosuppressive therapy carries a range of unwanted side effects, and tends to penalize the whole immune system. It is desirable to develop therapies that are more selective for antigen-reactive cells. As T lymphocytes use a wide range of surface receptors to interact with antigen-bearing cells and with each other, much interest is devoted to trying to develop agents that selectively block the interaction of these receptors with their ligands, and others that could be used to reprogram the immune system so that it might become tolerant to the antigens rather than attack them.


Attitudinal and demographic determinants of diet quality and implications for policy targeting.
Poor diet quality is a major public health concern that has prompted governments to introduce a range of measures to promote healthy eating. For these measures to be effective, they should target segments of the population with messages relevant to their needs, aspirations and circumstances. The present study investigates the extent to which attitudes and constraints influence healthy eating, as well as how these vary by demographic characteristics of the UK population. It further considers how such information may be used in segmented diet and health policy messages. A survey of 250 UK adults elicited information on conformity to dietary guidelines, attitudes towards healthy eating, constraints to healthy eating and demographic characteristics. Ordered logit regressions were estimated to determine the importance of attitudes and constraints in determining how closely respondents follow healthy eating guidelines. Further regressions explored the demographic characteristics associated with the attitudinal and constraint variables. People who attach high importance to their own health and appearance eat more healthily than those who do not. Risk-averse people and those able to resist temptation also eat more healthily. Shortage of time is considered an important barrier to healthy eating, although the cost of a healthy diet is not. These variables are associated with a number of demographic characteristics of the population; for example, young adults are more motivated to eat healthily by concerns over their appearance than their health. The approach employed in the present study could be used to inform future healthy eating campaigns. For example, messages to encourage the young to eat more healthily could focus on the impact of diets on their appearance rather than health.


Indigenous 14C-phenanthrene biodegradation in "pristine" woodland and grassland soils from Norway and the United Kingdom.
In this study, the indigenous microbial mineralisation of 14C-phenanthrene in seven background soils (four from Norwegian woodland and three from the UK (two grasslands and one woodland)) was investigated. ∑PAHs ranged from 16.39 to 285.54 ng g-1 dw soil. Lag phases (time before 14C-phenanthrene mineralisation reached 5%) were longer in all of the Norwegian soils and correlated positively with TOC, but negatively with ∑PAHs and phenanthrene degraders for all soils. 14C-phenanthrene mineralisation in the soils varied due to physicochemical properties. The results show that indigenous microorganisms can adapt to 14C-phenanthrene mineralisation following diffuse PAH contamination. Considering the potential of soil as a secondary PAH source, these findings highlight the important role of indigenous microflora in the processing of PAHs in the environment.


Molecular cloning and cell-specific growth characterization of polymorphic variants of type D serogroup 2 simian retroviruses.
Simian retroviruses (SRVs), the etiological agent of a spontaneous Simian acquired immunodeficiency syndrome, endemically infects large percentages of Asian macaques housed in biomedical research colonies and severely compromises the effective use of these species as a viable research animal. We recently described the molecular cloning of a serogroup 2 SRV, D2/RHE/OR, which causes mild immunosuppression in rhesus macaques. A restriction site variant, D2/RHE/OR/V1, has also been recovered from severely ill animals endemically infected with D2/RHE/OR. We now report the complete nucleotide sequences of D2/RHE/OR and D2/RHE/OR/V1. Both infectious molecular clones retain the genetic structure typical of type D SRVs (5' LTR-gag-prt-pol-env-3'LTR) and encode identically sized 8105-bp proviruses. D2/RHE/OR and D2/RHE/OR/V1 are 99.3% similar at the amino acid level, exhibiting only 17 residue differences, of which 10 are located in the envelope glycoproteins. The molecular clones and reciprocal chimeric viruses were used to assess the contribution of different genetic domains to virus infectivity in a T cell infection assay. These experiments indicate that D2/RHE/OR has a reduced ability to infect specific T cell lines, especially Hut-78 and MT-4 cells, and that the envelope gene is not the sole determinant of in vitro tropism.


Clinical Risk Factors Associated With Urethral Atrophy.
To analyze a series of clinical risk factors associated with pretreatment urethral atrophy. We retrospectively reviewed 301 patients who underwent artificial urinary sphincter (AUS) placement between September 2009 and November 2015; of these, 60 (19.9%) transcorporal cuff patients were excluded. Patients were stratified into 2 groups based on intraoperative spongiosal circumference measurements. Men with urethral atrophy (3.5 cm cuff size) were compared to controls (≥4 cm cuff size). Chi-square test, Mann-Whitney U test, and logistic regression analyses were performed to determine risk factors for urethral atrophy. Among 241 AUS patients analyzed, urethral atrophy was present in 151 patients (62.7%) compared to 90 patients (37.3%) who received larger cuffs (range 4-5.5 cm). Patients with urethral atrophy were older (71.1years vs 68.3 years; P < .02), more likely to have received radiation (52.9% vs. 33.3%; P < .007), and had a longer time interval between prostate cancer treatment and AUS surgery (8.9 years vs. 6.6 years; P < .033). On multivariable analysis, radiation therapy was independently associated with risk of urethral atrophy (odds ratio 1.77, 95% confidence interval: 1.01-3.13; P = .046), whereas greater time between cancer therapy and incontinence surgery approached clinical significance (odds ratio 1.05, 95% confidence interval 1.00-1.09; P = .05). History of radiation therapy and increasing length of time from prostate cancer treatment are associated with urethral atrophy before AUS placement.


Does Insight Affect the Efficacy of Antipsychotics in Acute Mania?: An Individual Patient Data Regression Meta-Analysis.
Patients having an acute manic episode of bipolar disorder often lack insight into their condition. Because little is known about the possible effect of insight on treatment efficacy, we examined whether insight at the start of treatment affects the efficacy of antipsychotic treatment in patients with acute mania. We used individual patient data from 7 randomized, double-blind, placebo-controlled registration studies of 4 antipsychotics in patients with acute mania (N = 1904). Insight was measured with item 11 of the Young Mania Rating Scale (YMRS) at baseline and study endpoint 3 weeks later. Treatment outcome was defined by (a) mean change score, (b) response defined as 50% or more improvement on YMRS, and (c) remission defined as YMRS score less than 8 at study endpoint. We used multilevel mixed effect linear (or logistic) regression analyses of individual patient data to assess the interaction between baseline insight and treatment outcomes. At treatment initiation, 1207 (63.5%) patients had impaired or no insight into their condition. Level of insight significantly modified the efficacy of treatment by mean change score (P = 0.039), response rate (P = 0.033), and remission rate (P = 0.043), with greater improvement in patients with more impaired insight. We therefore recommend that patients experiencing acute mania should be treated immediately and not be delayed until patients regain insight.


Sump bay fever: inhalational fever associated with a biologically contaminated water aerosol.
To investigate the clinical, serological, and environmental features of a work related inhalational fever associated with exposure to an aerosol generated from a biologically contaminated 130,000 gallon water pool in a building used for testing scientific equipment. Cross sectional survey of all exposed subjects (n = 83) by symptom questionnaire, clinical examination, spirometry, and serology for antibody to Pseudomonads, pool water extract, and endotoxin. In symptomatic patients diffusion capacity was measured, and chest radiology was performed if this was abnormal. Serial peak flow was recorded in those subjects with wheeze. Bacterial and fungal air sampling was performed before and during operation of the water pool pump mechanism. Endotoxin was measured in the trapped waters and in the pumps. Serum cotinine was measured as an objective indicator of smoking. Of the 20 symptomatic subjects, fever was most common in those with the highest exposure (chi 2 42.7, P < 0.001) in the sump bay when the water was (torrentially) recirculated by the water pumps. Symptoms occurred late in the working day only on days when the water pumps were used, and were independent of the serum cotinine. Pulmonary function was normal in most subjects (spirometry was normal in 79/83, diffusion capacity was low in five subjects, chest radiology was normal). Peak flow recording did not suggest a work relation. The bacterial content of the aerosol rose from 6 to > 10,000 colony forming units per cubic metre (cfu/m3) (predominantly environmental Pseudomonads) when the pumps were operating. High endotoxin concentrations were measured in the waters and oil sumps in the pumps. Low concentrations of antibody to the organisms isolated were detected (apart from two subjects with high antibody) but there was no relation to exposure or the presence of symptoms and similar antibody was found in the serum samples from a non-exposed population. The fever symptoms settled completely with the simple expedient of changing the water and cleaning the pumps. Given the results of our study, the development of inhalational fever in this unique environment and clearly restricted cohort was closely related to the degree of exposure to contaminated aerosol and mainly occurred in the absence of distinct serological abnormality and independent of cigarette smoking.


Release of serotonin from human platelets induced by aggregated immunoglobulins of different classes and subclasses.
The ability of human myeloma proteins of different classes and subclasses and of macroglobulins (all aggregated with bis-diazotized benzidine or heat) to aggregate washed human platelets and release [(3)H]-serotonin from the platelets was investigated and compared with the activity of normal IgG and tetanus-antitetanus IgG antigen-antibody complexes. Aggregated IgG1, IgG2, IgG3, IgG4, and normal IgG complexes all aggregated platelets and caused release of serotonin to similar extents. In contrast, IgA1, IgA2, IgD, and IgE myeloma proteins as well as IgM macroglobulins were completely inactive in this respect. Approximately 50% of the actvity remained in aggregated, mildly reduced and alkylated IgG myeloma proteins and their Fc fragments, whereas aggregated F(ab')(2) fragments were completely inactive. Addition of fresh serum inhibited the release of serotonin caused by aggregated IgG1 and IgG3 proteins and normal IgG antigen-antibody complexes by about 50% but had no effect upon the release of serotonin obtained with IgG2 and IgG4 proteins. This inhibition appeared to be mediated by complement. The release of serotonin was not accompanied by liberation of the cytoplasmic enzyme lactic dehydrogenase, indicating that no significant lysis of the platelets occurred. Addition of neutrophils did not enhance the serotonin release.


Improvement of Stability and Efficacy of C16Y Therapeutic Peptide via Molecular Self-Assembly into Tumor-Responsive Nanoformulation.
Peptide therapeutics hold great promise for the treatment of cancer due to low toxicity, high specificity, and ease of synthesis and modification. However, the unfavorable pharmacokinetic parameters strictly limit their therapeutic efficacy and clinical translation. Here, we tailor-designed an amphiphilic chimeric peptide through conjugation of functional 3-diethylaminopropyl isothiocyanate (DEAP) molecules to a short antitumor peptide, C16Y. The ultimate DEAP-C16Y peptides self-assembled into spherical nanostructures at physiologic conditions, which dissociated to release individual peptide molecules in weakly acidic tumors. DEAP-C16Y peptides showed negligible cytotoxicity but impaired vascular endothelial cell migration and tubule formation by inactivation of the focal adhesion kinase and PI3K-Akt pathways, as well as tumor cell invasion by decreasing invadopodia formation. Compared with C16Y, the systemically administered DEAP-C16Y nanostructures exhibited superior stability, thereby allowing prolonged treatment interval and resulting in significant decreases in microvessel density, tumor growth, and distant metastasis formation in orthotopic mammary tumor models. Through encapsulation of hydrophobic doxorubicin, DEAP-C16Y nanostructure served as a smart carrier to achieve targeted drug delivery and combination therapy. Our study, for the first time, demonstrates that a simple nanoformulation using a functional antitumor peptide as the building block can show innate antitumor activity and also provide a nanoplatform for combination therapy, opening a new avenue for the design of antitumor nanotherapeutics.


Biological aortic age derived from the arterial pressure waveform.
Indexes for arterial stiffness are, by their nature, influenced by the ambient blood pressure due to the curvilinear nature of arterial compliance. We developed a new concept of the "Modelflow aortic age," which is, theoretically, not influenced by the ambient blood pressure and provides an easily understood context (biological vs. chronological age) for measures of arterial stiffness. The purpose of the present study was to validate this pressure-independent index for aortic stiffness in humans. Twelve sedentary elderly (65-77 yr), 11 Masters athletes (65-73 yr), and 12 sedentary young individuals (20-42 yr) were studied. Modelflow aortic ages were comparable with chronological ages in both sedentary groups, indicating that healthy sedentary individuals have age-appropriate aortas. In contrast, Masters athletes showed younger Modelflow aortic ages than their chronological ages. The coefficient of variation of sedentary subjects was three times smaller with the Modelflow aortic age (21%) than with other indexes, such as static systemic arterial stiffness (61%), central pulse wave velocity (61%), or carotid β-stiffness index (58%). The typical error was very small and two times smaller in the Modelflow aortic age (<7%) than in static systemic arterial stiffness (>13%) during cardiac unloading by lower body negative pressure. The Modelflow aortic age can more precisely and reliably estimate aortic stiffening with aging and modifiers, such as life-long exercise training compared with the pressure-dependent index of static systemic arterial stiffness, and provides a physiologically relevant and clinically compelling context for such measurements.


Synthesis of functionalized indolizines via gold(i)-catalyzed intramolecular hydroarylation/aromatization of pyrrole-ynes.
A gold-catalyzed intramolecular hydroarylation/aromatization of pyrrole-ynes has been developed. This method provides a concise and straightforward route to functionalized indolizines through the construction of the pyridine ring of indolizines and also allows elaboration of its pyrrole moiety with or without functional groups. In addition, a wide variety of functional groups, such as aryl, alkenyl, alkynyl, pyridyl or thienyl groups, can be easily incorporated into the pyridine unit of the indolizine products under mild conditions. The utility of the indolizine products was demonstrated by their efficient transformations into various C3-functionalized indolizine derivatives.


Comparison of teen and adult driver crash scenarios in a nationally representative sample of serious crashes.
Motor vehicle crashes are the leading cause of death and acquired disability during the first four decades of life. While teen drivers have the highest crash risk, few studies examine the similarities and differences in teen and adult driver crashes. We aimed to: (1) identify and compare the most frequent crash scenarios-integrated information on a vehicle's movement prior to crash, immediate pre-crash event, and crash configuration-for teen and adult drivers involved in serious crashes, and (2) for the most frequent scenarios, explore whether the distribution of driver critical errors differed for teens and adult drivers. We analyzed data from the National Motor Vehicle Crash Causation Survey, a nationally representative study of serious crashes conducted by the U.S. National Highway Traffic Safety Administration from 2005 to 2007. Our sample included 642 16- to 19-year-old and 1167 35- to 54-year-old crash-involved drivers (weighted n=296,482 and 439,356, respectively) who made a critical error that led to their crash's critical pre-crash event (i.e., event that made the crash inevitable). We estimated prevalence ratios (PR) and 95% confidence intervals (CI) to compare the relative frequency of crash scenarios and driver critical errors. The top five crash scenarios among teen drivers, accounting for 37.3% of their crashes, included: (1) going straight, other vehicle stopped, rear end; (2) stopped in traffic lane, turning left at intersection, turn into path of other vehicle; (3) negotiating curve, off right edge of road, right roadside departure; (4) going straight, off right edge of road, right roadside departure; and (5) stopped in lane, turning left at intersection, turn across path of other vehicle. The top five crash scenarios among adult drivers, accounting for 33.9% of their crashes, included the same scenarios as the teen drivers with the exception of scenario (3) and the addition of going straight, crossing over an intersection, and continuing on a straight path. For two scenarios ((1) and (3) above), teens were more likely than adults to make a critical decision error (e.g., traveling too fast for conditions). Our findings indicate that among those who make a driver critical error in a serious crash, there are few differences in the scenarios or critical driver errors for teen and adult drivers.


A genome-wide association study identifies an osteoarthritis susceptibility locus on chromosome 7q22.
To identify novel genes involved in osteoarthritis (OA), by means of a genome-wide association study. We tested 500,510 single-nucleotide polymorphisms (SNPs) in 1,341 Dutch Caucasian OA cases and 3,496 Dutch Caucasian controls. SNPs associated with at least 2 OA phenotypes were analyzed in 14,938 OA cases and approximately 39,000 controls. Meta-analyses were performed using the program Comprehensive Meta-analysis, with P values <1 x 10(-7) considered genome-wide significant. The C allele of rs3815148 on chromosome 7q22 (minor allele frequency 23%; intron 12 of the COG5 gene) was associated with a 1.14-fold increased risk (95% confidence interval 1.09-1.19) of knee and/or hand OA (P = 8 x 10(-8)) and also with a 30% increased risk of knee OA progression (95% confidence interval 1.03-1.64) (P = 0.03). This SNP is in almost complete linkage disequilibrium with rs3757713 (68 kb upstream of GPR22), which is associated with GPR22 expression levels in lymphoblast cell lines (P = 4 x 10(-12)). Immunohistochemistry experiments revealed that G protein-coupled receptor protein 22 (GPR22) was absent in normal mouse articular cartilage or synovium. However, GPR22-positive chondrocytes were found in the upper layers of the articular cartilage of mouse knee joints that were challenged with in vivo papain treatment or methylated bovine serum albumin treatment. GPR22-positive chondrocyte-like cells were also found in osteophytes in instability-induced OA. Our findings identify a novel common variant on chromosome 7q22 that influences susceptibility to prevalence and progression of OA. Since the GPR22 gene encodes a G protein-coupled receptor, this is potentially an interesting therapeutic target.


Symbiodinium mitigate the combined effects of hypoxia and acidification on a noncalcifying cnidarian.
Anthropogenic nutrient inputs enhance microbial respiration within many coastal ecosystems, driving concurrent hypoxia and acidification. During photosynthesis, Symbiodinium spp., the microalgal endosymbionts of cnidarians and other marine phyla, produce O2 and assimilate CO2 and thus potentially mitigate the exposure of the host to these stresses. However, such a role for Symbiodinium remains untested for noncalcifying cnidarians. We therefore contrasted the fitness of symbiotic and aposymbiotic polyps of a model host jellyfish (Cassiopea sp.) under reduced O2 (~2.09 mg/L) and pH (~ 7.63) scenarios in a full-factorial experiment. Host fitness was characterized as asexual reproduction and their ability to regulate internal pH and Symbiodinium performance characterized by maximum photochemical efficiency, chla content and cell density. Acidification alone resulted in 58% more asexual reproduction of symbiotic polyps than aposymbiotic polyps (and enhanced Symbiodinium cell density) suggesting Cassiopea sp. fitness was enhanced by CO2 -stimulated Symbiodinium photosynthetic activity. Indeed, greater CO2 drawdown (elevated pH) was observed within host tissues of symbiotic polyps under acidification regardless of O2 conditions. Hypoxia alone produced 22% fewer polyps than ambient conditions regardless of acidification and symbiont status, suggesting Symbiodinium photosynthetic activity did not mitigate its effects. Combined hypoxia and acidification, however, produced similar numbers of symbiotic polyps compared with aposymbiotic kept under ambient conditions, demonstrating that the presence of Symbiodinium was key for mitigating the combined effects of hypoxia and acidification on asexual reproduction. We hypothesize that this mitigation occurred because of reduced photorespiration under elevated CO2 conditions where increased net O2 production ameliorates oxygen debt. We show that Symbiodinium play an important role in facilitating enhanced fitness of Cassiopea sp. polyps, and perhaps also other noncalcifying cnidarian hosts, to the ubiquitous effects of ocean acidification. Importantly we highlight that symbiotic, noncalcifying cnidarians may be particularly advantaged in productive coastal waters that are subject to simultaneous hypoxia and acidification.


Effectiveness of dry needling and injections of myofascial trigger points associated with plantar heel pain: a systematic review.
Plantar heel pain (plantar fasciitis) is one of the most common musculoskeletal pathologies of the foot. Plantar heel pain can be managed with dry needling and/or injection of myofascial trigger points (MTrPs) however the evidence for its effectiveness is uncertain. Therefore, we aimed to systematically review the current evidence for the effectiveness of dry needling and/or injections of MTrPs associated with plantar heel pain. We searched specific electronic databases (MEDLINE, EMBASE, AMED, CINAHL, SPORTDiscus and AMI) in April 2010 to identify randomised and non-randomised trials. We included trials where participants diagnosed with plantar heel pain were treated with dry needling and/or injections (local anaesthetics, steroids, Botulinum toxin A and saline) alone or in combination with acupuncture. Outcome measures that focussed on pain and function were extracted from the data. Trials were assessed for quality using the Quality Index tool. Three quasi-experimental trials matched the inclusion criteria: two trials found a reduction in pain for the use of trigger point dry needling when combined with acupuncture and the third found a reduction in pain using 1% lidocaine injections when combined with physical therapy. However, the methodological quality of the three trials was poor, with Quality Index scores ranging form 7 to 12 out of a possible score of 27. A meta-analysis was not conducted because substantial heterogeneity was present between trials. There is limited evidence for the effectiveness of dry needling and/or injections of MTrPs associated with plantar heel pain. However, the poor quality and heterogeneous nature of the included studies precludes definitive conclusions being made. Importantly, this review highlights the need for future trials to use rigorous randomised controlled methodology with measures such as blinding to reduce bias. We also recommend that such trials adhere to the Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) to ensure transparency.


A daily diary investigation of Latino ethnic identity, discrimination, and depression.
The objectives of the current study were to document the effects of discrimination on Latino mental health and to identify the circumstances by which ethnic identity serves a protective function. Instances of discrimination and depressive symptoms were measured every day for 13 days in a sample of Latino adults (N = 91). Multilevel random coefficient modeling showed a 1-day lagged effect in which increases in depression were observed the day following a discriminatory event. The findings also revealed differential effects of ethnic identity exploration and commitment. Whereas ethnic identity exploration was found to exacerbate the influence of daily discrimination on next-day depression, ethnic identity commitment operated as a stress buffer, influencing the intensity of and recovery from daily discrimination. The findings are discussed within a stress and coping perspective that identifies appropriate cultural resources for decreasing the psychological consequences associated with daily discrimination.


Technology and the Glaucoma Suspect.
To determine and compare the diagnostic performance of spectral-domain optical coherence tomography (SD-OCT), stereoscopic disc photographs, and automated perimetry as assessed by a group of glaucoma specialists in differentiating individuals with early glaucoma from suspects. Forty-six eyes (46 patients) with suspicious optic nerves had previously undergone SD-OCT scans, 24-2 visual fields (VFs), and optic disc photographs. The average VF mean deviation was -1.97 ± 2.09 (SD) dB. Four glaucoma specialists examined the 138 individual diagnostic tests and classified the patient as likely glaucomatous or nonglaucomatous based on the results of a single test. The diagnostic performances of each of the three tests were compared to a previously determined reference standard, based on the consensus of a separate panel of four glaucoma specialists who examined all three tests together. Among the four specialists, the interobserver agreement across the three diagnostic tests was poor for VF and photos, with kappa (κ) values of 0.13 and 0.16, respectively, and moderate for OCT, with κ value of 0.40. Using panel consensus as reference standard, OCT had the highest discriminative ability, with an area under the curve (AUC) of 0.99 (95% 0.96-1.0) compared to photograph AUC 0.85 (95% 0.73-0.96) and VF AUC 0.86 (95% 0.76-0.96), suggestive of closer performance to that of a group of glaucoma specialists. Compared to VF and disc photography, SD-OCT, when used alone, had better internal agreement as well as better agreement with the consensus of clinicians using all available data. Future studies should evaluate best practices for SD-OCT interpretation.


Early myoclonic status and outcome after cardiorespiratory arrest.
It has been suggested that early myoclonic status after cardiorespiratory arrest is an agonal event. Here we describe three cases who developed early myoclonic status during a coma after cardiorespiratory arrest due to acute asthma. As consciousness improved, each patient developed Lance-Adams type multifocal myoclonus, but the eventual outcome was satisfactory. Only one patient needed assistance to walk, and all three were self caring. One patient had persistent dyscalculia. Early myoclonic status is not necessarily an agonal event, particularly when it follows arrest due to acute asthma or asphyxia.


Sewage reflects the microbiomes of human populations.
Molecular characterizations of the gut microbiome from individual human stool samples have identified community patterns that correlate with age, disease, diet, and other human characteristics, but resources for marker gene studies that consider microbiome trends among human populations scale with the number of individuals sampled from each population. As an alternative strategy for sampling populations, we examined whether sewage accurately reflects the microbial community of a mixture of stool samples. We used oligotyping of high-throughput 16S rRNA gene sequence data to compare the bacterial distribution in a stool data set to a sewage influent data set from 71 U.S. cities. On average, only 15% of sewage sample sequence reads were attributed to human fecal origin, but sewage recaptured most (97%) human fecal oligotypes. The most common oligotypes in stool matched the most common and abundant in sewage. After informatically separating sequences of human fecal origin, sewage samples exhibited ~3× greater diversity than stool samples. Comparisons among municipal sewage communities revealed the ubiquitous and abundant occurrence of 27 human fecal oligotypes, representing an apparent core set of organisms in U.S. populations. The fecal community variability among U.S. populations was significantly lower than among individuals. It clustered into three primary community structures distinguished by oligotypes from either: Bacteroidaceae, Prevotellaceae, or Lachnospiraceae/Ruminococcaceae. These distribution patterns reflected human population variation and predicted whether samples represented lean or obese populations with 81 to 89% accuracy. Our findings demonstrate that sewage represents the fecal microbial community of human populations and captures population-level traits of the human microbiome. The gut microbiota serves important functions in healthy humans. Numerous projects aim to define a healthy gut microbiome and its association with health states. However, financial considerations and privacy concerns limit the number of individuals who can be screened. By analyzing sewage from 71 cities, we demonstrate that geographically distributed U.S. populations share a small set of bacteria whose members represent various common community states within U.S. adults. Cities were differentiated by their sewage bacterial communities, and the community structures were good predictors of a city's estimated level of obesity. Our approach demonstrates the use of sewage as a means to sample the fecal microbiota from millions of people and its potential to elucidate microbiome patterns associated with human demographics.


Binding affinity prediction of nanobody-protein complexes by scoring of molecular dynamics trajectories.
Nanobodies offer a viable alternative to antibodies for engineering high affinity binders. Their small size has an additional advantage: it allows exploiting computational protocols for optimizing their biophysical features, such as the binding affinity. The efficient prediction of this quantity is still considered a daunting task especially for modelled complexes. We show how molecular dynamics can successfully assist in the binding affinity prediction of modelled nanobody-protein complexes. The approximate initial configurations obtained by in silico design must undergo large rearrangements before achieving a stable conformation, in which the binding affinity can be meaningfully estimated. The scoring functions developed for the affinity evaluation of crystal structures will provide accurate estimates for modelled binding complexes if the scores are averaged over long finite temperature molecular dynamics simulations.


Determinants of oral self-care in the Brazilian adult population: a national cross-sectional study.
This study aims to investigate variables related to adherence to oral self-care in the Brazilian adult population. It is an exploratory study, using secondary data from a population-based survey on a representative sample of the adult population of the entire Brazilian territory (n=60202). The sample was selected using a multiple stage approach. The oral self-care indicator was defined by grouping the variables: periodicity of dentist appointments, use of dental floss, toothbrush and toothpaste, frequency of brushing and replacement of the toothbrush. The scores obtained from the indicator were categorized into adequate, partially adequate, and inadequate care. Statistical analysis consisted of dimensionality reduction, and oral self-care-related variables were submitted to logistic regression. The variables mostly related to inadequate or partially adequate oral self-care were: illiteracy (OR = 11.20, OR = 4.81), low educational level (OR = 3.50, OR = 1.96), negative oral health self-concept (OR=3.73, OR=1.74), absence of natural teeth (OR = 4.98, OR=2.60), edentulous lower arch (OR = 3.09; _____), number of missing upper teeth (OR=1.14, OR=1.05), absence of health insurance (OR=2.23, OR=2.07), sedentary lifestyle (OR=2.77, OR=1.51), and smoking (OR=2.18, OR=1.40). It was concluded that the individual's level of education is one of the main factors for adherence to adequate oral self-care, followed by level of oral health self-concept and tooth loss. Likewise, lifestyle also bears a significant influence.


Prostaglandin E2 stimulates granulocyte colony-stimulating factor production via the prostanoid EP2 receptor in mouse peritoneal neutrophils.
G-CSF is a hemopoietic growth factor involved in granulocytic differentiation of progenitor cells. In this study, we investigated the effects of PGE2 on G-CSF production in murine peritoneal neutrophils in vitro and in vivo. PGE2 augmented LPS-primed G-CSF release from peritoneal neutrophils. This augmentation was mimicked by a type E prostanoid receptor (EP)2-selective agonist but not by other EP-specific agonists. Indeed, the effect of PGE2 on G-CSF release was abolished in neutrophils isolated from EP2-deficient mice. PGE2 and an EP2 agonist have the ability to stimulate G-CSF gene expression even in the absence of LPS. In the casein-induced peritonitis model, the appearance of G-CSF in the casein-injected peritoneal cavity associated well with the timing of neutrophil infiltration as well as PGE2 levels in exudates, with a peak value at 6 h postinjection. Inhibition of endogenous PG synthesis by indomethacin resulted in a marked decrease in G-CSF content and neutrophil number in the peritoneal cavity. Moreover, EP2-deficient mice exhibited a strikingly reduced G-CSF content in peritoneal exudates with comparable responses in neutrophil migration and local PGE2 production at 6 h postinjection. These results suggest that the PGE2-EP2 system contributes to the local production of G-CSF during acute inflammation.


A new approach for in vitro imaging of breast cancer cells by anti-metadherin targeted PVA-pyrene.
Poly(vinyl alcohol)-pyrene-anti-metadherin (PVA-Py-(Anti-MTDH)), a novel antibody based water soluble probe containing both fluorescent and target sites in the structure for in vitro imaging of breast cancer cells is reported here. Since breast cancer cells have an excess of MDTH protein expressed on the surface, a PVA-Py prepared by "Click chemistry" approach is targeted by Anti-MTDH antibody and applied to the MCF-7 cell line. After characterization, the designed architecture was evaluated in terms of cell incorporation efficiency and compared with a non-targeted structure (PVA-Py). Atomic force microscopy (AFM) and fluorescence microscopy images of cells after incubation of the probe molecules were also obtained to monitor the interaction of the probes with the cancerous cells.


Identification of an erythrocyte component carrying the Duffy blood group Fya antigen.
The erythrocyte component carrying the Duffy blood group antigen Fya has been identified as a 35- to 43-kilodalton protein. The protein is degraded by proteases, chymotrypsin, and Pronase, which destroy its antigenicity on intact erythrocytes. Its unusual property of aggregating on being boiled in 5 percent sodium dodecyl sulfate with 5 percent 2-mercaptoethanol distinguishes it from other erythrocyte membrane proteins described to date.


High fidelity femtosecond pulses from an ultrafast fiber laser system via adaptive amplitude and phase pre-shaping.
The generation of high-fidelity femtosecond pulses is experimentally demonstrated in a fiber based chirped-pulse amplification (CPA) system through an adaptive amplitude and phase pre-shaping technique. A pulse shaper, based on a dual-layer liquid crystal spatial light modulator (LC-SLM), was implemented in the fiber CPA system for amplitude and phase shaping prior to amplification. The LC-SLM was controlled using a differential evolution algorithm, to maximize a two-photon absorption detector signal from the compressed fiber CPA output pulses. It is shown that this approach compensates for both accumulated phase from material dispersion and nonlinear phase modulation. A train of pulses was produced with an average power of 12.6W at a 50MHz repetition rate from our fiber CPA system, which were compressible to high fidelity pulses with a duration of 170 fs.


Performance analysis of the attenuation-partition based iterative phase retrieval algorithm for in-line phase-contrast imaging.
The phase retrieval is an important task in x-ray phase contrast imaging. The robustness of phase retrieval is especially important for potential medical imaging applications such as phase contrast mammography. Recently the authors developed an iterative phase retrieval algorithm, the attenuation-partition based algorithm, for the phase retrieval in inline phase-contrast imaging [1]. Applied to experimental images, the algorithm was proven to be fast and robust. However, a quantitative analysis of the performance of this new algorithm is desirable. In this work, we systematically compared the performance of this algorithm with other two widely used phase retrieval algorithms, namely the Gerchberg-Saxton (GS) algorithm and the Transport of Intensity Equation (TIE) algorithm. The systematical comparison is conducted by analyzing phase retrieval performances with a digital breast specimen model. We show that the proposed algorithm converges faster than the GS algorithm in the Fresnel diffraction regime, and is more robust against image noise than the TIE algorithm. These results suggest the significance of the proposed algorithm for future medical applications with the x-ray phase contrast imaging technique.


A DYNAMIC BAYESIAN NONLINEAR MIXED-EFFECTS MODEL OF HIV RESPONSE INCORPORATING MEDICATION ADHERENCE, DRUG RESISTANCE AND COVARIATES().
HIV dynamic studies have contributed significantly to the understanding of HIV pathogenesis and antiviral treatment strategies for AIDS patients. Establishing the relationship of virologic responses with clinical factors and covariates during long-term antiretroviral (ARV) therapy is important to the development of effective treatments. Medication adherence is an important predictor of the effectiveness of ARV treatment, but an appropriate determinant of adherence rate based on medication event monitoring system (MEMS) data is critical to predict virologic outcomes. The primary objective of this paper is to investigate the effects of a number of summary determinants of MEMS adherence rates on virologic response measured repeatedly over time in HIV-infected patients. We developed a mechanism-based differential equation model with consideration of drug adherence, interacted by virus susceptibility to drug and baseline characteristics, to characterize the long-term virologic responses after initiation of therapy. This model fully integrates viral load, MEMS adherence, drug resistance and baseline covariates into the data analysis. In this study we employed the proposed model and associated Bayesian nonlinear mixed-effects modeling approach to assess how to efficiently use the MEMS adherence data for prediction of virologic response, and to evaluate the predicting power of each summary metric of the MEMS adherence rates. In particular, we intend to address the questions: (i) how to summarize the MEMS adherence data for efficient prediction of virologic response after accounting for potential confounding factors such as drug resistance and covariates, and (ii) how to evaluate treatment effect of baseline characteristics interacted with adherence and other clinical factors. The approach is applied to an AIDS clinical trial involving 31 patients who had available data as required for the proposed model. Results demonstrate that the appropriate determinants of MEMS adherence rates are important in order to more efficiently predict virologic response, and investigations of adherence to ARV treatment would benefit from measuring not only adherence rate but also its summary metric assessment. Our study also shows that the mechanism-based dynamic model is powerful and effective to establish a relationship of virologic responses with medication adherence, virus resistance to drug and baseline covariates.


US birth weight/gestational age-specific neonatal mortality: 1995-1997 rates for whites, hispanics, and blacks.
In recent years, gains in neonatal survival have been most evident among very low birth weight, preterm, and low birth weight (LBW) infants. Most of the improvement in neonatal survival since the early 1980s seems to be the consequence of decreasing birth weight-specific mortality rates, which occurred during a period of increasing preterm and LBW rates. Although the decline in neonatal mortality has been widely publicized in the United States, research suggests that clinicians may still underestimate the chances of survival of an infant who is born too early or too small and may overestimate the eventuality of serious disability. So that clinicians may have current and needed ethnic- and race-specific estimates of the "chances" of early survival for newborn infants, we examined birth weight/gestational age-specific neonatal mortality rates for the 3 largest ethnic/racial groups in the United States: non-Hispanic whites, Hispanics, and non-Hispanic blacks. Marked racial variation in birth weight and gestational age-specific mortality has long been recognized, and growing concerns have been raised about ongoing and increasing racial disparities in pregnancy outcomes. Our purpose for this investigation was to provide an up-to-date national reference for birth weight/gestational age-specific neonatal mortality rates for use by clinicians in care decision making and discussions with parents. The National Center for Health Statistics linked live birth-infant death cohort files for 1995-1997 were used for this study. Singleton live births to US resident mothers with a reported maternal ethnicity/race of non-Hispanic white, non-Hispanic black, or Hispanic (n = 10 610 715) were selected for analysis. Birth weight/gestational age-specific neonatal mortality rates were calculated using 250 g/2-week intervals for each ethnic/racial group. The overall neonatal mortality rates for whites, Hispanics, and blacks were 3.24, 3.45, and 8.16 neonatal deaths per 1000 live births, and the proportion of births <28 weeks was 0.35%, 0.45%, and 1.39%, respectively. Newborns who weighed <1500 g comprised <2.5% of all births in each racial/ethnic group but accounted for >50% of neonatal deaths. For whites, Hispanics, and blacks, >50% of newborns 24 to 25 weeks of gestational age survived. For most combinations of birth weights <3500 g and gestational ages of <37 weeks, the neonatal mortality rate was lowest among blacks, compared with whites or Hispanics. At these same gestational age/birth weight combinations, Hispanics have slightly lower mortality rates than whites. For combinations of birth weights >3500 g and gestational ages of 37 to 41 weeks, Hispanics had the lowest neonatal mortality rate. In these birth weight/gestational age combinations, where approximately two thirds of births occur, blacks had the highest neonatal mortality rate. Compared with earlier reports, these data suggest that a substantial improvement in birth weight/gestational age-specific neonatal mortality has occurred in the United States. Regardless of ethnicity/race, the risk of a neonatal death does not exceed 50% (the suggested definition for the limit of viability), except for birth weights below 500 g and gestational ages <24 weeks. Notwithstanding, ethnic/racial variations in neonatal mortality rates continue to persist, both in overall rates and within birth weight/gestational age categories. Blacks continue to have higher proportions for preterm and LBW births, compared with either whites or Hispanics. At the same time, blacks experience lower risks of neonatal mortality for preterm and LBW infants, while having higher risks of mortality among term, postterm, normal birth weight, and macrosomic births.


Lung development and susceptibility to ventilator-induced lung injury.
Ventilator-induced lung injury has been predominantly studied in adults. To explore the effects of age and lung development on susceptibility to such injury. Ex vivo isolated nonperfused rat lungs (infant, juvenile, and adult) were mechanically ventilated where VT was based on milliliters per kilogram of body weight or as a percentage of the measured total lung capacity (TLC). In vivo anesthetized rats (infant, adult) were mechanically ventilated with pressure-limited VTs. Allocation to ventilation strategy was randomized. Ex vivo injury was assessed by pressure-volume analysis, reduction in TLC, and histology, and in vivo injury by lung compliance, cytokine production, and wet- to dry-weight ratio. Ex vivo ventilation (VT 30 ml.kg(-1)) resulted in a significant reduction (36.0 +/- 10.1%, p < 0.05) in TLC in adult but not in infant lungs. Ex vivo ventilation (VT 50% TLC) resulted in a significant reduction in TLC in both adult (27.8 +/- 2.8%) and infant (10.6 +/- 7.0%) lungs, but more so in the adult lungs (p < 0.05); these changes were paralleled by histology and pressure-volume characteristics. After high stretch in vivo ventilation, adult but not infant rats developed lung injury (total lung compliance, wet/dry ratio, tumor necrosis factor alpha). Surface video microscopy demonstrated greater heterogeneity of alveolar distension in ex vivo adult versus infant lungs. These data provide ex vivo and in vivo evidence that comparable ventilator settings are significantly more injurious in the adult than infant rat lung, probably reflecting differences in intrinsic susceptibility or inflation pattern.


Phylogenetic ANOVA: The Expression Variance and Evolution Model for Quantitative Trait Evolution.
A number of methods have been developed for modeling the evolution of a quantitative trait on a phylogeny. These methods have received renewed interest in the context of genome-wide studies of gene expression, in which the expression levels of many genes can be modeled as quantitative traits. We here develop a new method for joint analyses of quantitative traits within- and between species, the Expression Variance and Evolution (EVE) model. The model parameterizes the ratio of population to evolutionary expression variance, facilitating a wide variety of analyses, including a test for lineage-specific shifts in expression level, and a phylogenetic ANOVA that can detect genes with increased or decreased ratios of expression divergence to diversity, analogous to the famous Hudson Kreitman Aguadé (HKA) test used to detect selection at the DNA level. We use simulations to explore the properties of these tests under a variety of circumstances and show that the phylogenetic ANOVA is more accurate than the standard ANOVA (no accounting for phylogeny) sometimes used in transcriptomics. We then apply the EVE model to a mammalian phylogeny of 15 species typed for expression levels in liver tissue. We identify genes with high expression divergence between species as candidates for expression level adaptation, and genes with high expression diversity within species as candidates for expression level conservation and/or plasticity. Using the test for lineage-specific expression shifts, we identify several candidate genes for expression level adaptation on the catarrhine and human lineages, including genes putatively related to dietary changes in humans. We compare these results to those reported previously using a model which ignores expression variance within species, uncovering important differences in performance. We demonstrate the necessity for a phylogenetic model in comparative expression studies and show the utility of the EVE model to detect expression divergence, diversity, and branch-specific shifts.


Learning in action: developing safety improvement capabilities through action learning.
Patient safety is one of the greatest challenges facing health care today and nurses are well placed to find opportunities for enhancing care and making it safer. Nurse education has an important role to play in ensuring future professions have capabilities and confidence to meet this challenge however this requires new pedagogies in nurse education. This paper reports on an initiative to develop the safety improvement and leadership capabilities of final year nursing students using Action Learning to support students to undertake a safety improvement project in the clinical setting. A qualitative, interpretive research approach was used to explore students' experiences of participation in Action Learning. 52 nursing students from a UK University participated in the study. Student accounts of their experiences were generated through focus group and individual interviews and data were subject to thematic analysis. Findings are discussed in relation to three categories including "creating an enabling environment", "learning through action and reflection" and "the emergence of safety improvement and leadership practices." The study findings provide valuable insights into how AL processes can engender personal leadership capabilities and support students to make a valuable contribution to safer care practices, both as students and as future health care professionals.


NEM modification prevents high-affinity ATP binding to the first nucleotide binding fold of the sulphonylurea receptor, SUR1.
Pancreatic beta-cell ATP-sensitive potassium channels, composed of SUR1 and Kir6.2 subunits, serve as a sensor for intracellular nucleotides and regulate glucose-induced insulin secretion. To learn more about the interaction of SUR1 with nucleotides, we examined the effect of N-ethylmaleimide (NEM) modification. Photoaffinity labeling of SUR1 with 5 microM 8-azido-[alpha-32P]ATP or 8-azido-[gamma-32P]ATP was inhibited by NEM with Ki of 1.8 microM and 2.4 microM, and Hill coefficients of 0.94 and 1.1, respectively. However, when the cysteine residue in the Walker A motif of the first nucleotide binding fold (NBF1) of SUR1 was replaced with serine (C717S), photoaffinity labeling was not inhibited by 100 microM NEM. These results suggest that NBF1 of SUR1 has a NEM-sensitive structure similar to that of NBF1 of MDR1, a multidrug transporter, and confirm NBF1 as the high-affinity ATP binding site on SUR1.


Effect, number and location of synapses made by single pyramidal cells onto aspiny interneurones of cat visual cortex.
1. Dual intracellular recordings were made from synaptically coupled pyramidal cell-to-interneurone pairs (n = 5) of the cat visual cortex in vitro. Pre- and postsynaptic neurones were labelled with biocytin, followed by correlated light and electron microscopic analysis to determine all sites of synaptic interaction. 2. Pyramidal neurones in layers II-III elicited monosynaptic EPSPs in three distinct classes of smooth dendritic local-circuit neurones, namely basket cells (n = 3), a dendrite-targeting cell (n = 1) and a double bouquet cell (n = 1). Unitary EPSPs in basket cells were mediated by one, two, and two synaptic junctions, whereas the pyramid-to-dendrite-targeting cell and pyramid-to-double bouquet cell interaction were mediated by five and seven synaptic junctions, respectively. Recurrent synaptic junctions were found on all somato-dendritic compartments, with a tendency to be clustered close to the soma on the double bouquet and dendrite-targeting cells. The latter interneurones were reciprocally connected with pyramidal cells. 3. Unitary EPSPs had an average peak amplitude of 1005 +/- 518 microV, fast rise times (10-90%; 0.67 +/- 0.25 ms) and were of short duration (at half-amplitude, 4.7 +/- 1.0 ms). Their decay was monoexponential (tau = 7.8 +/- 4.3 ms) at hyperpolarized membrane potentials and appeared to be shaped by passive membrane properties (tau = 9.2 +/- 8.5 ms). All parameters of concomitantly recorded spontaneous EPSPs were remarkably similar (mean amplitude, 981 +/- 433 microV; mean rise time, 0.68 +/- 0.18 ms; mean duration, 4.7 +/- 1.7 ms). 4. In all three pyramidal-to-basket cell pairs, closely timed (10-50 ms) pairs of presynaptic action potentials resulted in statistically significant paired-pulse depression, the mean of the averaged second EPSPs being 80 +/- 11% of the averaged conditioning event. The overall degree of paired-pulse modulation was relatively little affected by either the amplitude of the preceding event or the inter-event interval. 5. The probability density function of the peak amplitudes of the unitary EPSPs could be adequately fitted with a quantal model. Without quantal variance, however, the minimum number of components in the model, excluding the failures, exceeded the number of electron microscopically determined synaptic junctions for all five connections. In contrast, incorporating quantal variance gave a minimum number of components which was compatible with the number of synaptic junctions, and which fitted the data equally well as models incorporating additional components but no quantal variance. For this model with quantal variance with the minimum number of components the estimate of the quantal coefficient of variation ranged between 0.33 and 0.46, and the corresponding quantal sizes ranged between 260 and 657 microV. The peak EPSP amplitudes in two of the four connections with more than one synaptic junction could be adequately described by a uniform binomial model for transmitter release. 6. In conclusion, at least three distinct interneurone classes receive local excitatory pyramidal cell input which they relay to different compartments on their postsynaptic target neurones. The reliability of transmission is high, but the fast time course of the EPSPs constrains their temporal summation. Due to the relatively small amplitude of unitary EPSPs several convergent inputs will therefore be required to elicit suprathreshold responses.


Subunit composition of mammalian transient receptor potential channels in living cells.
Hormones, neurotransmitters, and growth factors give rise to calcium entry via receptor-activated cation channels that are activated downstream of phospholipase C activity. Members of the transient receptor potential channel (TRPC) family have been characterized as molecular substrates mediating receptor-activated cation influx. TRPC channels are assumed to be composed of multiple TRPC proteins. However, the cellular principles governing the assembly of TRPC proteins into homo- or heteromeric ion channels still remain elusive. By pursuing four independent experimental approaches--i.e., subcellular cotrafficking of TRPC subunits, differential functional suppression by dominant-negative subunits, fluorescence resonance energy transfer between labeled TRPC subunits, and coimmunoprecipitation--we investigate the combinatorial rules of TRPC assembly. Our data show that (i) TRPC2 does not interact with any known TRPC protein and (ii) TRPC1 has the ability to form channel complexes together with TRPC4 and TRPC5. (iii) All other TRPCs exclusively assemble into homo- or heterotetramers within the confines of TRPC subfamilies--e.g., TRPC4/5 or TRPC3/6/7. The principles of TRPC channel formation offer the conceptual framework to assess the physiological role of distinct TRPC proteins in living cells.


[Evaluating the utility of MODIS vegetation index for monitoring agricultural drought].
The exclusive shortwave bands provided by MODIS sensors offer new opportunities for agricultural drought monitoring, since they are very sensitive to vegetation moisture. In the present work, we selected Songnen Plain in Northeast China as study area aiming at monitoring agricultural drought of dry farmland here. Four types of vegetation water indices and vegetation greenness indices were calculated from the 8-day composite MODIS product (MODO9A1) in vegetation growing season between 2001 and 2010, respectively. Multi-scale standardized precipitation index (SPI) derived from precipitation data of weather stations was used as reference data to estimate drought sensitivity of various vegetation indices, and a pixel-to-weather station paired correlation approach was used to calculate the Pearson correlation coefficient between vegetation index and SPIs. The result indicated that vegetation water indices established by near infrared and shortwave infrared bands outperformed vegetation greenness indices based on visible and near infrared bands. Of these indices, NDII7 performs the best with highest correlation coefficients across all SPIs. The authors' results demonstrated the potential of MODIS shortwave spectral bands in monitoring agricultural drought, and this provides new insights to future research.


Evaluating the epsilon-domination based multi-objective evolutionary algorithm for a quick computation of Pareto-optimal solutions.
Since the suggestion of a computing procedure of multiple Pareto-optimal solutions in multi-objective optimization problems in the early Nineties, researchers have been on the look out for a procedure which is computationally fast and simultaneously capable of finding a well-converged and well-distributed set of solutions. Most multi-objective evolutionary algorithms (MOEAs) developed in the past decade are either good for achieving a well-distributed solutions at the expense of a large computational effort or computationally fast at the expense of achieving a not-so-good distribution of solutions. For example, although the Strength Pareto Evolutionary Algorithm or SPEA (Zitzler and Thiele, 1999) produces a much better distribution compared to the elitist non-dominated sorting GA or NSGA-II (Deb et al., 2002a), the computational time needed to run SPEA is much greater. In this paper, we evaluate a recently-proposed steady-state MOEA (Deb et al., 2003) which was developed based on the epsilon-dominance concept introduced earlier(Laumanns et al., 2002) and using efficient parent and archive update strategies for achieving a well-distributed and well-converged set of solutions quickly. Based on an extensive comparative study with four other state-of-the-art MOEAs on a number of two, three, and four objective test problems, it is observed that the steady-state MOEA is a good compromise in terms of convergence near to the Pareto-optimal front, diversity of solutions, and computational time. Moreover, the epsilon-MOEA is a step closer towards making MOEAs pragmatic, particularly allowing a decision-maker to control the achievable accuracy in the obtained Pareto-optimal solutions.


Correlation of antinuclear antibody immunofluorescence patterns with immune profile using line immunoassay in the Indian scenario.
Immunity status, individual response to disease and types of antibodies produced are well known to vary from person to person, place to place and probably from population to population. A broad spectrum of specific auto antibodies that have so far been associated with specific rheumatic diseases, as noted in Western literature, has been well taken as a reference standard all over the world. There is neither research work nor any data correlating the auto antibodies and their antinuclear antibody (ANA) patterns with the immunoprofile in the Indian population to date. To understand a definite association between ANA patterns and specific antibodies in the serum in the Indian study population and to document similarities / differences with the West. This prospective and retrospective double blind study was undertaken on the South Indian population referred for ANA testing by Indirect Immunofluorescence method and by immunoline methods. Serum samples of patients from a random South Indian population who sought medical help for rheumatic disease were subjected for ANA testing by indirect immunofluorescence (IIF) method and line immunoassay during the study period of 27 months. Serum samples were processed in dilution of 1:100 using HEp - 2010 / liver biochip (Monkey) (EUROIMMUN AG). The serum samples which were further processed for line immunoassay were treated in 1:100 dilution on nylon strips coated with recombinant and purified antigens as discrete lines with plastic backing (EUROIMMUN AG) coated with antigens nRNP / Sm, Sm, SSA, Ro-52, SSB, Scl-70, PM-Scl, PCNA, Jo-1, CENP-B, dsDNA, nucleosomes, histones, ribosomal protein-P, anti-mitochondrial antibodies (AMA-M2) along with a control band. The analysis was done by comparing the intensity of the reaction with positive control line by image analysis. The antinuclear antibody indirect immunofluorescence (ANA - IIF) patterns obtained were projectable to visualize a certain spectrum of specific antibodies such as homogenous (45.5%) with dsDNA, nucleosomes, histones, SSA / Ro-52, RIB and RNP / Sm, speckled pattern (35.6%) with Sm, RNP, SSA/Ro-52, SSB, Sm and RIB; nucleolar pattern with Scl-70, Sm, RNP and centromere pattern with CENP-B. The methodology indicated that, cytoplasmic pattern noted in ANA also needs to be correlated with primate liver in a biochip, which should prompt further decision for a request for line immunoassay and it is preferable for two pathologists to report independently and sign out a consensus ANA report for better predictive value. As a definite correlation between the ANA patterns and the group of antibodies was detected by line immunoassay, one could predict presence of certain specific auto antibodies for a particular ANA pattern identified. This may restrict one from requesting for line immunoassay, which is expensive and economizes on the cost of laboratory investigations in a developing country like India. Thus, screening of sera by ANA-IIF method alone may suffice and probably reduce the expense of detailed immunological work-up with minimal loss in diagnostic accuracy. This study, the first of its kind in India, provides database and reference for the Indian subpopulation.


Salvage surgical procedure for artificial sphincter extrusion.
Case Hypothesis: Surgical removal is the standard treatment for artificial sphincter extrusion. However in some specific situations is possible to maintain the prosthesis with good results. We report a 60 years old patient presenting sphincter pump extrusion one month after artificial urinary sphincter (AUS) AMS 800™ placement for treating post-radical prostatectomy urinary incontinence (PRPUI). He also had a penile prosthesis implant one year before that was replaced in the same surgery the sphincter was implanted. As patient refused sphincter removal and there were no signals of active infection he was treated by extensive surgical washing with antibiotics and antiseptics. Pump was repositioned in the opposite side of the scrotum. Patient had good evolution with sphincter activation 50 days later. After 10 months of follow up, patient is socially continent and having regular sexual intercourse. Savage surgery may be an option in select cases of artificial sphincter extrusion. Promising future implications: Like in some patients with penile prosthesis some patients with artificial sphincter extrusion can be treated without removing the device. This may be a line of research about conservative treatment of artificial sphincter complications.


Recruitment strategies and the retention of obese urban racial/ethnic minority adolescents in clinical trials: the FIT families project, Michigan, 2010-2014.
The successful recruitment and retention of participants is integral to the translation of research findings. We examined the recruitment and retention rates of racial/ethnic minority adolescents at a center involved in the National Institutes of Health Obesity Research for Behavioral Intervention Trials (ORBIT) initiative by the 3 recruitment strategies used: clinic, informatics, and community. During the 9-month study, 186 family dyads, each composed of an obese African American adolescent and a caregiver, enrolled in a 6-month weight-loss intervention, a sequential multiple assignment randomized trial. We compared recruitment and retention rates by recruitment strategy and examined whether recruitment strategy was related to dyad baseline characteristics. Of the 186 enrolled families, 110 (59.1%) were recruited through clinics, 53 (28.5%) through informatics, and 23 (12.4%) through community. Of those recruited through community, 40.4% enrolled in the study, compared with 32.7% through clinics and 8.2% through informatics. Active refusal rate was 3%. Of the 1,036 families identified for the study, 402 passively refused to participate: 290 (45.1%) identified through informatics, 17 (29.8%) through community, and 95 (28.3%) through clinics. Recruitment strategy was not related to the age of the adolescent, adolescent comorbidities, body mass index of the adolescent or caregiver, income or education of the caregiver, or retention rates at 3 months, 7 months, or 9 months. Study retention rate was 87.8%. Using multiple recruitment strategies is beneficial when working with racial/ethnic minority adolescents, and each strategy can yield good retention. Research affiliated with health care systems would benefit from the continued specification, refinement, and dissemination of these strategies.


Impaired JAK-STAT signal transduction contributes to growth hormone resistance in chronic uremia.
Chronic renal failure (CRF) is associated with resistance to the growth-promoting and anabolic actions of growth hormone (GH). In rats with CRF induced by partial renal ablation, 7 days of GH treatment had a diminished effect on weight gain and hepatic IGF-1 and IGFBP-1 mRNA levels, compared with sham-operated pair-fed controls. To assess whether GH resistance might be due to altered signal transduction, activation of the JAK-STAT pathway was studied 10 or 15 minutes after intravenous injection of 5 mg/kg GH or vehicle. Hepatic GH receptor (GHR) mRNA levels were significantly decreased in CRF, but GHR protein abundance and GH binding to microsomal and plasma membranes was unaltered. JAK2, STAT1, STAT3, and STAT5 protein abundance was also unchanged. However, GH-induced tyrosine phosphorylation of JAK2, STAT5, and STAT3 was 75% lower in the CRF animals. Phosphorylated STAT5 and STAT3 were also diminished in nuclear extracts. The expression of the suppressor of cytokine signaling-2 (SOCS-2) was increased twofold in GH-treated CRF animals, and SOCS-3 mRNA levels were elevated by 60% in CRF, independent of GH treatment. In conclusion, CRF causes a postreceptor defect in GH signal transduction characterized by impaired phosphorylation and nuclear translocation of GH-activated STAT proteins, which is possibly mediated, at least in part, by overexpression of SOCS proteins.


Intracellular serine protease of Bacillus subtilis: sequence homology with extracellular subtilisins.
Intracellular serine protease was isolated from stationary-grown Bacillus subtilis A-50 cells and purified to homogeneity. The molecular weight of the enzyme is 31,000 +/- 1,000, with an isoelectric point of 4.3. Its amino acid composition is characteristically enriched in glutamic acid content, differing from that of extra-cellular subtilisins. The enzyme is completely inhibited with phenylmethylsulfonyl fluoride and ethylenediaminetetraacetic acid. Intracellular protease possesses negligible activity towards bovine serum albumin and hemoglobin, but has 5- to 20-fold higher specific activity against p-nitroanilides of benzyloxycarbonyl tripeptides than subtilisin BPN'. Esterolytic activity of the enzyme is also higher than that of subtilisin BPN'. The enzyme is sequence homologous with secretory subtilisins throughout 50 determined NH2-terminal residues, indicating the presence of duplicated structural genes for serine proteases in the B. subtilis genome. The occurrence of two homologous genes in the cell might accelerate the evolution of serine protease not only by the loosening of selective constrainst, but also by creation of sequence variants by means of intragenic recombination. Three molecular forms of intracellular protease were found, two of them with NH2-terminal glutamic acid and one minor form, three residues longer, with asparagine as NH2 terminus. These data indicate the possible presence of an enzyme precursor proteolytically modified during cell growth.


Vital Signs: Update on Zika Virus-Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure - U.S. Zika Pregnancy Registry, 2016.
In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%-7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%-14%]). Birth defects were reported in 15% (95% CI = 8%-26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.


Learning to trust: social feedback normalizes trust behavior in first-episode psychosis and clinical high risk.
Psychosis is characterized by problems in social functioning that exist well before illness onset, and in individuals at clinical high risk (CHR) for psychosis. Trust is an essential element for social interactions that is impaired in psychosis. In the trust game, chronic patients showed reduced baseline trust, impaired response to positive social feedback, and attenuated brain activation in reward and mentalizing areas. We investigated whether first-episode psychosis patients (FEP) and CHR show similar abnormalities in the neural and behavioral mechanisms underlying trust. Twenty-two FEP, 17 CHR, and 43 healthy controls performed two trust games, with a cooperative and an unfair partner in the fMRI scanner. Region of interest analyses were performed on mentalizing and reward processing areas, during the investment and outcome phases of the games. Compared with healthy controls, FEP and CHR showed reduced baseline trust, but like controls, learned to trust in response to cooperative and unfair feedback. Symptom severity was not associated with baseline trust, however in FEP associated with reduced response to feedback. The only group differences in brain activation were that CHR recruited the temporo-parietal junction (TPJ) more than FEP and controls during investment in the unfair condition. This hyper-activation in CHR was associated with greater symptom severity. Reduced baseline trust may be associated with risk for psychotic illness, or generally with poor mental health. Feedback learning is still intact in CHR and FEP, as opposed to chronic patients. CHR however show distinct neural activation patterns of hyper-activation of the TPJ.


Mycobacterium tuberculosis dihydrofolate reductase is not a target relevant to the antitubercular activity of isoniazid.
Mycobacterium tuberculosis enoyl-acyl-ACP reductase (InhA) has been demonstrated to be the primary target of isoniazid (INH). Recently, it was postulated that M. tuberculosis dihydrofolate reductase (DHFR) is also a target of INH, based on the findings that a 4R-INH-NADP adduct synthesized from INH by a nonenzymatic approach showed strong inhibition of DHFR in vitro, and overexpression of M. tuberculosis dfrA in M. smegmatis conferred a 2-fold increase of resistance to INH. In the present study, a plasmid expressing M. tuberculosis dfrA was transformed into M. smegmatis and M. tuberculosis strains, respectively. The transformant strains were tested for their resistance to INH. Compared to the wild-type strains, overexpression of dfrA in M. smegmatis and M. tuberculosis did not confer any resistance to INH based on the MIC values. Similar negative results were obtained with 14 other overexpressed proteins that have been proposed to bind some form of INH-NAD(P) adduct. An Escherichia coli cell-based system was designed that allowed coexpression of both M. tuberculosis katG and dfrA genes in the presence of INH. The DHFR protein isolated from the experimental sample was not found bound with any INH-NADP adduct by enzyme inhibition assay and mass spectroscopic analysis. We also used whole-genome sequencing to determine whether polymorphisms in dfrA could be detected in six INH-resistant clinical isolates known to lack mutations in inhA and katG, but no such mutations were found. The dfrA overexpression experiments, together with the biochemical and sequencing studies, conclusively demonstrate that DHFR is not a target relevant to the antitubercular activity of INH.


Improving pan-genome annotation using whole genome multiple alignment.
Rapid annotation and comparisons of genomes from multiple isolates (pan-genomes) is becoming commonplace due to advances in sequencing technology. Genome annotations can contain inconsistencies and errors that hinder comparative analysis even within a single species. Tools are needed to compare and improve annotation quality across sets of closely related genomes. We introduce a new tool, Mugsy-Annotator, that identifies orthologs and evaluates annotation quality in prokaryotic genomes using whole genome multiple alignment. Mugsy-Annotator identifies anomalies in annotated gene structures, including inconsistently located translation initiation sites and disrupted genes due to draft genome sequencing or pseudogenes. An evaluation of species pan-genomes using the tool indicates that such anomalies are common, especially at translation initiation sites. Mugsy-Annotator reports alternate annotations that improve consistency and are candidates for further review. Whole genome multiple alignment can be used to efficiently identify orthologs and annotation problem areas in a bacterial pan-genome. Comparisons of annotated gene structures within a species may show more variation than is actually present in the genome, indicating errors in genome annotation. Our new tool Mugsy-Annotator assists re-annotation efforts by highlighting edits that improve annotation consistency.


First Report of Verticillium Wilt Caused by Verticillium nonalfalfae on Tree-of-Heaven (Ailanthus altissima) in Ohio.
Verticillium wilt of the highly invasive tree-of-heaven [Ailanthus altissima (Mill.) Swingle], caused by Verticillium nonalfalfae Interbitzin et al. (1), formerly classified as V. albo-atrum Reinke and Berthold, has been reported in the United States from two states: Pennsylvania (2) and Virginia (3). Infected A. altissima in both states exhibited similar symptoms of wilt, premature defoliation, terminal dieback, yellow vascular discoloration, and mortality. In June 2012, the second author observed dead and dying A. altissima trees in southern Ohio (Pike County) that exhibited symptoms similar to those on diseased A. altissima trees in Pennsylvania and Virginia. Samples were collected from stems of three symptomatic A. altissima trees and sent to Penn State for morphological and molecular identification. Immediately upon arrival, samples were surface-disinfected and plated onto plum extract agar (PEA), a semi-selective medium for Verticillium spp., amended with neomycin and streptomycin (2). The samples yielded six isolates, two from each of the three symptomatic trees, all of which were putatively identified as V. nonalfalfae based on the presence of verticillate conidiophores and formation of melanized hyphae. DNA was extracted from three isolates and molecular analyses performed using known primers (1) coding for elongation factor 1-alpha (EF), glyceraldehyde-3-phosphate dehydrogenase (GPD), and tryptophan synthase (TS). A BLAST search generated sequences that revealed 100% similarity to V. nonalfalfae for all three protein coding genes among the three Ohio isolates and reference sequences from Ailanthus, including isolates VnAaPA140 (GenBank Accession Nos. KC307764, KC307766, and KC307768) and VnAaVA2 (KC307758, KC307759, and KC307760), as well as isolate PD592 from potato (JN188227, JN188163, and JN188035), thereby confirming taxonomic placement of the Ohio Ailanthus isolates among those recovered from Ailanthus in Pennsylvania and Virginia. Aligned sequences from one representative isolate, VnAaOH1, were deposited into GenBank as accessions KC307761 (EF), KC307762 (GPD), and KC307763 (TS). In August 2012, the pathogenicity of all six isolates was confirmed by root-dipping 10 healthy 3-week-old A. altissima seedlings (seeds collected in University Park, PA) into conidial suspensions of 1 × 107 cfu/ml, wherein all inoculated seedlings wilted and died within 4 and 9 weeks, respectively. V. nonalfalfae was reisolated from all inoculated seedlings; control seedlings inoculated with distilled water remained asymptomatic. Ohio is the third state from which V. nonalfalfae has been reported to be pathogenic on A. altissima. If V. nonalfalfae proves to be widespread, it may represent a natural biocontrol for the invasive A. altissima. Also, since USDA APHIS evaluates and regulates new potential biocontrol agents on a state-by-state basis, it is important to document each state in which V. nonalfalfae is killing A. altissima, so that in-state inoculum can be used for biocontrol efforts, simplifying the regulatory process. References: (1) P. Inderbitzin et al. 2011 PLoS ONE, 6, e28341, 2011. (2) M. J. Schall and D. D. Davis. Plant Dis. 93:747, 2009. (3) A. L. Snyder et al. Plant Dis. 96:837, 2013.


Oxidative damage in age-related macular degeneration.
Epidemiologic studies have suggested that elderly patients who consumed diets rich in antioxidants throughout their lives are less likely to be afflicted with age-related macular degeneration (AMD). This led to the Age-Related Eye Disease Study, which showed that supplements containing antioxidant vitamins and zinc reduce the risk of progression to severe stages of AMD. Despite these data that indirectly implicate oxidative damage in the pathogenesis of AMD, there has not been any direct demonstration of increased oxidative damage in the retinas of patients with AMD. In this study, we used biomarkers of oxidative damage in postmortem eyes from patients with AMD and comparably aged patients without AMD to directly assess for oxidative damage. Sections from 4 eyes with no pathologic features of AMD showed no immunofluorescent staining for markers of oxidative damage, while sections from 8 of 12 eyes with advanced geographic atrophy showed evidence of widespread oxidative damage in both posterior and anterior retina. Only 2 of 8 eyes with choroidal neovascularization and 2 of 16 eyes with diffuse drusen and no other signs of AMD showed evidence of oxidative damage. These data suggest that widespread oxidative damage occurs in the retina of some patients with AMD and is more likely to be seen in patients with advanced geographic atrophy. This does not rule out oxidative damage as a pathogenic mechanism in patients with CNV, but suggests that a subpopulation of patients with geographic atrophy may have a major deficiency in the oxidative defense system that puts the majority of cells in the retina at risk for oxidative damage.


The Developmental Trajectory of the Operational Momentum Effect.
Mental calculation is thought to be tightly related to visuospatial abilities. One of the strongest evidence for this link is the widely replicated operational momentum (OM) effect: the tendency to overestimate the result of additions and to underestimate the result of subtractions. Although the OM effect has been found in both infants and adults, no study has directly investigated its developmental trajectory until now. However, to fully understand the cognitive mechanisms lying at the core of the OM effect it is important to investigate its developmental dynamics. In the present study, we investigated the development of the OM effect in a group of 162 children from 8 to 12 years old. Participants had to select among five response alternatives the correct result of approximate addition and subtraction problems. Response alternatives were simultaneously presented on the screen at different locations. While no effect was observed for the youngest age group, children aged 9 and older showed a clear OM effect. Interestingly, the OM effect monotonically increased with age. The increase of the OM effect was accompanied by an increase in overall accuracy. That is, while younger children made more and non-systematic errors, older children made less but systematic errors. This monotonous increase of the OM effect with age is not predicted by the compression account (i.e., linear calculation performed on a compressed code). The attentional shift account, however, provides a possible explanation of these results based on the functional relationship between visuospatial attention and mental calculation and on the influence of formal schooling. We propose that the acquisition of arithmetical skills could reinforce the systematic reliance on the spatial mental number line and attentional mechanisms that control the displacement along this metric. Our results provide a step in the understanding of the mechanisms underlying approximate calculation and an important empirical constraint for current accounts on the origin of the OM effect.


Long-term changes in abundances of Sonoran Desert lizards reveal complex responses to climatic variation.
Understanding how climatic variation affects animal populations and communities is essential for addressing threats posed by climate change, especially in systems where impacts are projected to be high. We evaluated abundance dynamics of five common species of diurnal lizards over 25 years in a Sonoran Desert transition zone where precipitation decreased and temperature increased across time, and assessed hypotheses for the influence of climatic flux on spatiotemporal variation in abundances. We repeatedly surveyed lizards in spring and summer of each year at up to 32 sites, and used hierarchical mixture models to estimate detection probabilities, abundances, and population growth rates. Among terrestrial species, abundances of a short-lived, winter-spring breeder increased markedly by an estimated 237%-285% across time, while two larger spring-summer breeders with higher thermal preferences declined by up to 64%. Abundances of two arboreal species that occupy shaded and thus sheltered microhabitats fluctuated but did not decline systematically. Abundances of all species increased with precipitation at short lag times (1-1.5 years) likely due to enhanced food availability, but often declined after periods of high precipitation at longer lag times (2-4 years) likely due to predation and other biotic pressures. Although rising maximum daily temperatures (Tmax ) are expected to drive global declines of lizards, associations with Tmax were variable and weak for most species. Instead, abundances of all species declined with rising daily minimum temperatures, suggesting degradation of cool refugia imposed widespread metabolic or other costs. Our results suggest climate warming and drying are having major impacts on lizard communities by driving declines in species with traits that augment exposure to abiotic extremes and by modifying species interactions. The complexity of patterns we report indicates that evaluating and responding to the influence of climate change on biodiversity must consider a broad array of ecological processes.


Use of a pressure-sensing walkway system for biometric assessment of gait characteristics in goats.
The purpose of this study was to quantitatively assess gait characteristics and weight-bearing forces during ambulation in goats free of lameness using a pressure-sensing walkway as a biometric tool for stride, gait, and force analysis. Forty-six non-lame adult goats ranging in age from 5 to 6 years, mixed-breeds, and with a mean body weight of 52 ± 7.1 kgs were used. Goats were trained to walk over a pressure-sensing walkway. Data for analysis was collected on 2 different days, 3 days apart. On each day, 2 to 5 walking passes, in the same direction, were captured for each goat. Data from 2 valid passes meeting the criteria for consistent walking gait on each day were averaged then used for analysis. Analysis was performed, including the day-effect, for stride, gait, and force characteristics. Of the 46 goats enrolled in the study, complete data sets were achieved in 33 (72%) goats. Gait biometrics were similar among the assessment days; therefore, all data was pooled for the purpose of characterizing data for individual limb and biometric parameter comparisons at the individual goat level. Statistical analysis revealed that no difference within the paired limbs, and that there were significant differences between the front limbs and hind limbs. Maximum force and maximum peak pressure were significantly greater for the front limbs as compared with the hind limbs (p < 0.001). Based on the results, gait and force characteristics can be consistently measured in goats using a pressure-sensing walkway during a consistent walking gait. Goats apply greater force to the forelimbs during the weight-bearing phase of stride as compared with the hind limbs. The use of objective assessment tools is expected to improve the ability of researchers and clinicians to monitor changes in weight bearing and gait and will contribute to improved animal welfare.


Spontaneous interferon production by pulmonary leukocytes is associated with lentivirus-induced lymphoid interstitial pneumonia.
Ovine lentiviruses share genome sequence, structural features, and replicative mechanisms with HIV, the etiologic agent of AIDS. A lamb model of lentivirus-induced lymphoid interstitial pneumonia, comparable to lymphoid interstitial pneumonia associated with pediatric AIDS, was used to investigate production of leukocyte-soluble mediators. Lentivirus-infected lambs and adult sheep with severe lymphoid interstitial pneumonia had significantly elevated levels of spontaneous interferon (IFN) production from pulmonary leukocytes compared with ovine lentiviruses-infected animals with mild or no lesions of lymphoid interstitial pneumonia or non-infected controls. However, peripheral blood mononuclear cells from lentivirus-infected lambs did not spontaneously release significant amounts of IFN. IFN production by pulmonary lymph node lymphocytes was enhanced in the presence of lentivirus-infected alveolar macrophages. Animals with lentivirus-induced disease and spontaneous IFN production had enhanced virus replication within tissues. The ovine lentiviruses-induced IFN had a m.w. of between 25,000 and 35,000 and was resistant to freeze/thawing procedures. The IFN activity was sensitive to trypsin and stable to low pH and heat. IFN with similar physical and biochemical properties was produced when ovine lentiviruses was added to control leukocyte cultures. IL-2 and PGE2 production and responses to mitogen by pulmonary lymph node lymphocytes of lentivirus-diseased lambs were not statistically different from control animals. Increased local production of IFN in lentivirus-infected host tissues may serve to accelerate the entry of leukocytes into virus-induced lesions promoting cell-mediated tissue damage and also provide increased numbers of cells for virus replication.


Auditory conflict resolution correlates with medial-lateral frontal theta/alpha phase synchrony.
When multiple persons speak simultaneously, it may be difficult for the listener to direct attention to correct sound objects among conflicting ones. This could occur, for example, in an emergency situation in which one hears conflicting instructions and the loudest, instead of the wisest, voice prevails. Here, we used cortically-constrained oscillatory MEG/EEG estimates to examine how different brain regions, including caudal anterior cingulate (cACC) and dorsolateral prefrontal cortices (DLPFC), work together to resolve these kinds of auditory conflicts. During an auditory flanker interference task, subjects were presented with sound patterns consisting of three different voices, from three different directions (45° left, straight ahead, 45° right), sounding out either the letters "A" or "O". They were asked to discriminate which sound was presented centrally and ignore the flanking distracters that were phonetically either congruent (50%) or incongruent (50%) with the target. Our cortical MEG/EEG oscillatory estimates demonstrated a direct relationship between performance and brain activity, showing that efficient conflict resolution, as measured with reduced conflict-induced RT lags, is predicted by theta/alpha phase coupling between cACC and right lateral frontal cortex regions intersecting the right frontal eye fields (FEF) and DLPFC, as well as by increased pre-stimulus gamma (60-110 Hz) power in the left inferior fontal cortex. Notably, cACC connectivity patterns that correlated with behavioral conflict-resolution measures were found during both the pre-stimulus and the pre-response periods. Our data provide evidence that, instead of being only transiently activated upon conflict detection, cACC is involved in sustained engagement of attentional resources required for effective sound object selection performance.


Induction of rabbit lung CYP4A4 prostaglandin omega-hydroxylase by various steroid hormones.
Cytochrome P4504A4 (CYP4A4) is expressed at low basal levels in adult rabbit lungs, but is significantly induced during pregnancy by an unknown mechanism. As the gradual rise in CYP4A4 levels appears to coincide with the progressive increase in several steroid hormones throughout pregnancy, we examined the induction of CYP4A4 after treatment with various steroid hormones by monitoring both the CYP4A4 mRNA level and the CYP4A4-specific prostaglandin E(1) (PGE(1)) omega-hydroxylation reaction in rabbit lung microsomes. Treatment with progesterone and/or a synthetic glucocorticoid (dexamethasone) resulted in a significant increase in PGE(1) omega-hydroxylase activity, whereas estradiol, aldosterone, dehydroepiandrosterone, and dehydroepiandrosterone sulfate did not. These studies indicated that dexamethasone was a more potent inducer of CYP4A4 than progesterone. Simultaneous injection of dexamethasone and glucocorticoid/progesterone antagonists (RU38486, RU40555, or RU43044) inhibited the increase in PGE(1) omega-hydroxylase activity as well as mRNA levels by approximately 50%. In addition, simultaneous treatment with both dexamethasone and progesterone did not result in an additive or synergistic effect on PGE(1) omega-hydroxylase activity. These data indicate that, while distinctive receptors for glucocorticoid and/or progesterone are involved, induction may also require common or interacting regulatory elements (yet to be determined) in the CYP4A4 gene. These findings implicate both of these steroid receptors (PR/GR) in the induction of CYP4A4 in rabbit lung.


CMOS compatible polarization splitter using hybrid plasmonic waveguide.
We design and experimentally demonstrate an ultrashort integrated polarization splitter on silicon-on-insulator (SOI) platform. Our polarization splitter uses a hybrid plasmonic waveguide as the middle waveguide in a three-core arrangement to achieve large birefringence, allowing only transverse-magnetic (TM) polarized light to directionally couple to the cross port of the directional coupler. Finite-difference time-domain (FDTD) and eigenmode expansive (EME) calculations show that the splitter can achieve an extinction ratio of greater than 15 dB with less than 0.5 dB insertion losses. The polarization splitter was fabricated on SOI platform using standard complementary metal-oxide-semiconductor (CMOS) technology and measured at telecommunications wavelengths. Extinction ratios of 12.3 dB and 13.9 dB for the transverse-electric (TE) and TM polarizations were obtained, together with insertion losses of 2.8 dB and 6.0 dB.