A patient with loin hematuria syndrome and chronic flank pain treated with pulsed radiofrequency of the splanchnic nerves.
Chronic abdominal and flank pain can be multifactorial and difficult to treat. Loin pain hematuria syndrome (LPHS) is a rare clinical cause of chronic abdominal and flank pain and is a diagnosis of exclusion with limited treatment options, ranging from medications to renal autotransplantation or even nephrectomy in resistant cases. A 50-year-old man with a history of recurrent nephrolithiasis secondary to hypercalcemia presented to the pain clinic with bilateral flank pain. After failed conservative medical management, the decision was made to proceed to interventional modalities. He responded for a short duration to a splanchnic nerve block and subsequently had a longer analgesic response to pulsed radiofrequency (PRF) ablation to the splanchnic nerves. LPHS is a difficult clinical scenario to diagnose and treat. Conservative options are often unsuccessful, but the more extreme interventions such as renal autotransplantation and nephrectomies are invasive and not always effective. In this case report, we describe the novel use of PRF to the splanchnic nerves as an alternative treatment modality for patients with LPHS.Although the exact mechanism of action of PRF on nerve tissue is unclear, its indication in pain management requires further research and discussion. Our patient experienced substantial and sustained relief of his flank pain. PRF may be a viable option for patients with LPHS.


Pre-stimulus alpha oscillations over somatosensory cortex predict tactile misperceptions.
Fluctuations of pre-stimulus oscillatory activity in the somatosensory alpha band (8-14Hz) observed using human EEG and MEG have been shown to influence the detection of supra- and peri-threshold somatosensory stimuli. However, some reports of touch occur even without a stimulus. We investigated the possibility that pre-stimulus alpha oscillations might also influence these false reports of touch - known as tactile misperceptions. We recorded EEG while participants performed the Somatic Signal Detection Task (SSDT), in which participants must detect brief, peri-threshold somatosensory targets. We found that pre-stimulus oscillatory power in the somatosensory alpha range exhibited a negative linear relationship with reporting of touch at electrode clusters over both contralateral and ipsilateral somatosensory regions. As pre-stimulus alpha power increased, the probability of reporting a touch declined; as it decreased, the probability of reporting a touch increased. This relationship was stronger on trials without a somatosensory stimulus than on trials with a somatosensory stimulus, although was present for both trial types. Spatio-temporal cluster-based permutation analysis also found that pre-stimulus alpha was lower on trials when touch was reported - irrespective of whether it was present - over contralateral and ipsilateral somatosensory cortices, as well as left frontocentral areas. We argue that alpha power may reflect changes in response criterion rather than sensitivity alone. Low alpha power relates to a low barrier to reporting a touch even when one is not present, while high alpha power is linked to less frequent reporting of touch overall.


Drinking water quality in the glacial aquifer system, northern USA.
Groundwater supplies 50% of drinking water worldwide, but compromised water quality from anthropogenic and geogenic contaminants can limit usage of groundwater as a drinking water source. Groundwater quality in the glacial aquifer system, USA (GLAC), is presented in the context of a hydrogeologic framework that divides the study area into 17 hydrogeologic terranes. Results are reported at aquifer-system scale and regional (terrane) scale. This paper presents a quantitative assessment of groundwater quality in the GLAC using data from numerous sources for samples collected 2005-2013, compared to health-based and aesthetic (non-health) benchmarks, and evaluated with areal and population metrics. Concentrations above a benchmark are considered high. Trace elements are widespread across the study area, with an estimated 5.7 million people relying on groundwater with high concentrations of one or more trace elements; manganese and arsenic are most often at high concentration. Nitrate is found at high concentration in 4.0% of the study area, serving about 740 thousand people. Organic compounds including pesticides and volatile organic compounds are high in 2.0% of the assessed study area, with about 870 thousand people relying on groundwater with high concentrations of an organic compound. High arsenic and manganese concentrations occur primarily in the terranes with thick, stratigraphically complex, fine-grained glacial sediment, coincident with groundwater under reducing conditions (indicated by iron concentrations >100 μg/L); high nitrate is uncommon in those same terranes. When nitrate is high in thick, fine-grained, complex terranes, though, it is much more commonly associated with groundwater under more oxidizing conditions. Common geogenic trace elements occur at high concentration due to characteristic geologic and geochemical conditions. Conversely, anthropogenic nitrate and organic compounds are introduced at or near the land surface. High concentrations of nitrate or organic compounds are generally limited to areas in proximity where people live and use the chemicals.


Role of Lymphadenectomy for Uterine Sarcoma: A Meta-Analysis.
Uterine sarcomas are rare, highly aggressive tumors with an unfavorable prognosis. The role of lymphadenectomy (LAD) remains controversial for this particular tumor type. To examine whether LAD can assist in prognosis or clinical benefits for uterine sarcoma patients, we performed a meta-analysis based on published studies. We initially identified published studies by searching the PubMed database up to 30 November 2015. Study quality was evaluated systematically using the Newcastle-Ottawa Scale for assessing the quality of studies for inclusion in meta-analyses. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using Stata software version 12.0. Our search retrieved 14 eligible studies, involving a total of 4867 patients, including 1356 (27.9%) patients who had LAD. The pooled RR for uterine leiomyosarcoma (uLMS) in patients with LAD in 5 trials was 0.90 (95% CI, 0.62-1.31) and for endometrial stromal sarcoma (ESS) in 11 trials was 0.96 (95% CI, 0.69-1.34), suggesting that there was no significant benefit of LAD in improving overall survival (P < 0.05). A random-effects model was chosen to estimate the RRs in view of the significant heterogeneity in the included studies (uLMS: Cochran Q test: P = 0.022, I = 64.9%; ESS: Cochran Q test: P = 0.005, I = 60.1%). No publication bias was detected by the Egger and Begg tests (uLMS: Begg: P = 0.221, Egger: P = 0.148; ESS: Begg: P = 1.000, Egger: P = 0.928). Based on currently available evidence, the findings of this meta-analysis suggest that LAD bears little prognostic or therapeutic benefit in patients with uterine sarcoma. Systematic LAD may not be recommended in patients with uLMS or ESS unless the patient has obvious extrauterine involvement, clinically suspicious enlarged nodes, or advanced sarcomas.


Joint blood flow is more sensitive to inflammatory arthritis than oxyhemoglobin, deoxyhemoglobin, and oxygen saturation.
Joint hypoxia plays a central role in the progression and perpetuation of rheumatoid arthritis (RA). Thus, optical techniques that can measure surrogate markers of hypoxia such as blood flow, oxyhemoglobin, deoxyhemoglobin, and oxygen saturation are being developed to monitor RA. The purpose of the current study was to compare the sensitivity of these physiological parameters to arthritis. Experiments were conducted in a rabbit model of RA and the results revealed that joint blood flow was the most sensitive to arthritis and could detect a statistically significant difference (p<0.05, power = 0.8) between inflamed and healthy joints with a sample size of only four subjects. Considering that this a quantitative technique, the high sensitivity to arthritis suggests that joint perfusion has the potential to become a potent tool for monitoring disease progression and treatment response in RA.


The history of anxiety symptoms among 171 primary alcoholics.
This study used patient and resource person face-to-face interviews to explore the history of anxiety symptoms and syndromes in 171 primary alcoholic male veterans on an alcohol treatment program. Almost all men (98%) reported at least one symptom of anxiety during drinking or withdrawal, including 80% who related problems with palpitations and/or shortness of breath. In addition, seven men (4%) described at least one episode of panic lasting from 1 to 4 or more hours, although only two of these individuals experienced three or more panic attacks in a 3-week period in the context of heavy drinking or withdrawal. No men evidenced repetitive panic attacks either before the onset of heavy drinking or in the context of a protracted period of abstinence. Seven individuals (4%) fulfilled criteria for generalized anxiety symptoms when dry for 3 or more months. The histories of treatment by mental health workers or in psychiatric facilities taken together with the symptom picture generated from patient and resource person interviews do not indicate an elevated incidence of either panic disorder or generalized anxiety that is independent of heavy drinking.


Cumulative impact of common genetic variants and other risk factors on colorectal cancer risk in 42,103 individuals.
Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data. Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39,266) and in combination with gender, age and FH (n=11,324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks. The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2 × 10(-16)), confirmed in external validation sets (Sweden p=1.2 × 10(-6), Finland p=2 × 10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk. Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.


APC mutations are sufficient for the growth of early colorectal adenomas.
It is not clear whether APC mutations are sufficient for early colorectal adenomas to grow or whether additional mutations at other loci are required. We previously have screened 210 early colorectal adenomas from familial adenomatous polyposis patients for mutations and allelic loss at APC. Here, we determined whether allelic loss at APC had any effect on the nearby alpha-catenin gene. However, loss on 5q in familial adenomatous polyposis adenomas rarely extended as far as alpha-catenin, and no differences in alpha-catenin protein expression were found in tumors that showed loss encompassing both APC and alpha-catenin. We then screened all 210 tumors for mutations at candidate loci other than APC (K-ras, beta-catenin, and allelic loss at 1p33-p35 and 1p36) and for microsatellite instability (MSI). Each of these loci has been implicated previously in early colorectal tumorigenesis. One tumor harbored a beta-catenin mutation and another MSI, but none showed K-ras mutation or allelic loss at 1p33-p35 or 1p36. These data support the following hypotheses derived from sporadic colorectal tumors: beta-catenin mutations are generally an alternative to mutations at APC, MSI is not usually an early phenomenon in colorectal tumorigenesis, and K-ras mutations are more typical of large- and moderate-sized adenomas. Contrary to some previous reports, chromosome 1p allelic loss is infrequent in very early adenomas. APC mutations are generally sufficient for colorectal tumors to grow to about 1-cm diameter, although chance mutations at other loci can provide these early colorectal adenomas with a selective advantage, and some colorectal tumors may develop along a pathway not involving APC.


Positional information in root epidermis is defined during embryogenesis and acts in domains with strict boundaries.
Cell position rather than cell lineage governs most aspects of development in plants. However, the nature and the origin of positional information remains elusive. Animal epidermal patterning relies in many cases on positional information provided by cell-cell communication. The epidermal layer of the Arabidopsis root is made of alternating files of two cell types and thus presents a simple pattern to study positional mechanisms. Clonal analysis of the root epidermis in combination with molecular and morphological markers has shown that cell fate is determined by position relative to the underlying cell layer, the cortex. The epidermal pattern appears to be organised during embryogenesis. Fate is not fixed in the developing root, though, as cells that move into a position previously occupied by neighbour cells ablated using laser microsurgery change fate. In contrast, cell fate is not altered when communication with living neighbour cells is impaired. Precise mapping of the influence of the position of extracellular cues on cell fate has shown that domains of positional information are organised with well-defined boundaries. Cell-fate specification in the root epidermis relies on positional information that is organised in stable domains with sharp boundaries. The epidermal pattern is defined during embryogenesis and positional information remains active in the root until the initiation of cell morphogenesis. The origin of some positional cues might be extracellular.


Corticosteroid-induced hyperglycemia is increased 10-fold in patients with pemphigus.
This study aimed to highlight the importance of routine screening for hyperglycemia and to develop a standardized, evidence-based approach for the management of pemphigus patients on prolonged systemic corticosteroid (CS) therapy. A cross-sectional study was conducted in two university-affiliated teaching hospitals using a referred sample of 200 patients with a confirmed diagnosis of pemphigus vulgaris, pemphigus foliaceus, or mucous membrane pemphigoid. All patients were receiving systemic CS therapy. A total of 150 patients responded to the survey. Six participants were excluded and 144 were included. The main outcome measure was blood glucose level to detect hyperglycemia. New-onset hyperglycemia was identified in 40% of patients who received CS therapy. None of the expected variables, including age, body mass index, family history of diabetes, corticosteroid dose, and duration of corticosteroid therapy, were independently associated with new-onset hyperglycemia. These findings indicate that the prevalence of CS-induced hyperglycemia in pemphigus patients is 40% and that in patients with pemphigus or MMP, CS therapy is associated with a markedly increased risk for hyperglycemia (odds ratio = 10.7, 95% confidence interval 1.38-83.50) compared with that of patients with the same diseases who do not receive CS therapy.


Insurance status and the use of guideline therapy in the treatment of selected cancers.
This study estimates the impact of type of insurance coverage on the receipt of guideline therapy in a population-based sample of cancer patients treated in the community. Patients (n = 7,134) from the National Cancer Institute's Patterns of Care studies who were newly diagnosed with 11 different types of cancer were analyzed. The definition of guideline therapy was based on the National Comprehensive Cancer Network treatment recommendations. Insurance status was categorized as a mutually exclusive hierarchical variable (no insurance, any private insurance, any Medicaid, Medicare only, and all other). Multivariate analyses were used to examine the association between insurance and receipt of guideline therapy. Adjusting for clinical and nonclinical variables, insurance status was a modest, although statistically significant, determinant of receipt of guideline therapy, with 65% of the privately insured patients receiving recommended therapy compared with 60% of patients with Medicaid. Seventy percent of the uninsured patients received guideline therapy, which was nonsignificantly different compared with private insurance. When stratified by race, insurance was a statistically significant predictor of the receipt of guideline therapy only for non-Hispanic blacks. Overall, levels of guideline treatment were lower than expected and particularly low for patients with Medicaid or Medicare only. The use of guideline therapy for ovarian and cervical cancer patients and for patients with rectal cancers was unrelated to type of insurance. Of particular concern is the significantly lower use of guideline therapy for non-Hispanic black patients with Medicaid. After adjusting for other factors, only half of these patients received guideline therapy.


Influence of fermentable carbohydrates or protein on large intestinal and urinary metabolomic profiles in piglets.
It was recently shown that variations in the ratio of dietary fermentable carbohydrates (fCHO) and fermentable protein (fCP) differentially affect large intestinal microbial ecology and the mucosal response. Here we investigated the use of mass spectrometry to profile changes in metabolite composition in colon and urine associated with variation in dietary fCHO and fCP composition and mucosal physiology. Thirty-two weaned piglets were fed 4 diets in a 2 × 2 factorial design with low fCP and low fCHO, low fCP and high fCHO, high fCP and low fCHO, and high fCP and high fCHO. After 21 to 23 d, all pigs were euthanized and colon digesta and urine metabolite profiles were obtained by mass spectrometry. Analysis of mass spectra by partial least squares approach indicated a clustering of both colonic and urinary profiles for each pig by feeding group. Metabolite identification and annotation using the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways revealed increased abundance of metabolites associated with arachidonic acid metabolism in colon of pigs fed a high concentration of fCP irrespective of dietary fCHO. Urinary metabolites did not show as clear patterns. Mass spectrometry can effectively differentiate metabolite profiles in colon contents and urine associated with changes in dietary composition. Whether metabolite profiling is an effective tool to identify specific metabolites (biomarkers) or metabolite profiles associated with gut function and integrity needs further elucidation.


Depleted uranium: all the questions about DU and Gulf War syndrome are not yet answered.
For 15 years, the debate about depleted uranium (DU) and its detrimental effects on the health of veterans of the Gulf War of 1991, on the Iraqi people and military (and subsequently on the people of Kosovo, Afghanistan, and Iraq during the second war) has remained unresolved. Meanwhile, the number of Gulf War veterans who have developed the so-called Gulf War syndrome has risen to about one-third of the 800,000 U.S. forces deployed, and unknown proportions of those involved in the subsequent wars. Uncounted civilians and personnel of other nations that fought in Iraq and other wars since 1991 have also been afflicted. The veterans have suffered from multiple serious physiological disorders and have received little or no official recognition, medical relief, or compensation. We need to take another look at this issue, using a holistic and interactive model for the toxic matrix of exposures, identifying the major roadblocks to resolving the scientific questions, and finding appropriate medical and political responses. This commentary is such an attempt.


Clinical and preclinical translation of cell-based therapies using adipose tissue-derived cells.
Adipose tissue is now recognized as an accessible, abundant, and reliable site for the isolation of adult stem cells suitable for tissue engineering and regenerative medicine applications. The past decade has witnessed an explosion of preclinical data relating to the isolation, characterization, cryopreservation, differentiation, and transplantation of freshly isolated stromal vascular fraction cells and adherent, culture-expanded, adipose-derived stromal/stem cells in vitro and in animal models. This body of work has provided evidence supporting clinical translational applications of adipose-derived cells in safety and efficacy trials. The present article reviews the case reports and phase I-III clinical evidence using autologous adipose-derived cells that have been published, to date, in the fields of gastroenterology, neurology, orthopedics, reconstructive surgery, and related clinical disciplines. Future directions and challenges facing the field are discussed and evaluated.


An examination of needlestick injury rates, hepatitis B vaccination uptake and instruction on 'sharps' technique among medical students.
A 12-question survey designed to examine venepuncture techniques and instruction and uptake of hepatitis B vaccination was completed by 172 of the 275 medical students to whom it was distributed (a response rate of 62.5%). Seventy-five injuries were reported, at an average of 0.3 per student per year. Of the respondents, 63% resheathed needles after use, a practice frequently cited as a cause of needlestick injury. However, in this sample resheathing was not significantly associated with a higher or lower injury rate (chi 2 = 2.07, P > 0.1). Of the respondents from the most recent intake, only 20 out of 57 had completed a course of hepatitis B vaccinations prior to the commencement of venepuncture duties. There was almost universal ignorance concerning the correct course of action following 'sharps' injury. Recommendations are made concerning hepatitis B vaccination and teaching strategies for medical students.


Development of an objective gene expression panel as an alternative to self-reported symptom scores in human influenza challenge trials.
Influenza challenge trials are important for vaccine efficacy testing. Currently, disease severity is determined by self-reported scores to a list of symptoms which can be highly subjective. A more objective measure would allow for improved data analysis. Twenty-one volunteers participated in an influenza challenge trial. We calculated the daily sum of scores (DSS) for a list of 16 influenza symptoms. Whole blood collected at baseline and 24, 48, 72 and 96 h post challenge was profiled on Illumina HT12v4 microarrays. Changes in gene expression most strongly correlated with DSS were selected to train a Random Forest model and tested on two independent test sets consisting of 41 individuals profiled on a different microarray platform and 33 volunteers assayed by qRT-PCR. 1456 probes are significantly associated with DSS at 1% false discovery rate. We selected 19 genes with the largest fold change to train a random forest model. We observed good concordance between predicted and actual scores in the first test set (r = 0.57; RMSE = -16.1%) with the greatest agreement achieved on samples collected approximately 72 h post challenge. Therefore, we assayed samples collected at baseline and 72 h post challenge in the second test set by qRT-PCR and observed good concordance (r = 0.81; RMSE = -36.1%). We developed a 19-gene qRT-PCR panel to predict DSS, validated on two independent datasets. A transcriptomics based panel could provide a more objective measure of symptom scoring in future influenza challenge studies. Trial registration Samples were obtained from a clinical trial with the ClinicalTrials.gov Identifier: NCT02014870, first registered on December 5, 2013.


A hybrid frame concealment algorithm for H.264/AVC.
In packet-based video transmissions, packets loss due to channel errors may result in the loss of the whole video frame. Recently, many error concealment algorithms have been proposed in order to combat channel errors; however, most of the existing algorithms can only deal with the loss of macroblocks and are not able to conceal the whole missing frame. In order to resolve this problem, in this paper, we have proposed a new hybrid motion vector extrapolation (HMVE) algorithm to recover the whole missing frame, and it is able to provide more accurate estimation for the motion vectors of the missing frame than other conventional methods. Simulation results show that it is highly effective and significantly outperforms other existing frame recovery methods.


Clinical and electrographic features of sunflower syndrome.
Sunflower Syndrome describes reflex seizures - typically eyelid myoclonia with or without absence seizures - triggered when patients wave their hands in front of the sun. While valproate has been recognized as the best treatment for photosensitive epilepsy, many clinicians now initially treat with newer medications; the efficacy of these medications in Sunflower Syndrome has not been investigated. We reviewed all cases of Sunflower Syndrome seen at our institution over 15 years to describe the clinical course, electroencephalogram (EEG), and treatment response in these patients. Search of the electronic medical record and EEG database, as well as survey of epilepsy providers at our institution, yielded 13 cases of Sunflower Syndrome between 2002 and 2017. We reviewed the records and EEG tracings. Patients were mostly young females, with an average age of onset of 5.5 years. Seven had intellectual, attentional or academic problems. Self-induced seizures were predominantly eyelid myoclonia ± absences and 6 subjects also had spontaneous seizures. EEG demonstrated a normal background with 3-4 Hz spike waves ± polyspike waves as well as a photoparoxysmal response. Based on both clinical and EEG response, valproate was the most effective treatment for reducing or eliminating seizures and improving the EEG; 9 patients tried valproate and 66% had significant improvement or resolution of seizures. None of the nine patients on levetiracetam or seven patients on lamotrigine monotherapy achieved seizure control, though three patients had improvement with polypharmacy. Valproate monotherapy continues to be the most effective treatment for Sunflower Syndrome and should be considered early. For patients who cannot tolerate valproate, higher doses of lamotrigine or polypharmacy should be considered. Levetiracetam monotherapy, even at high doses, is unlikely to be effective.


Herb-drug interactions with St John's wort (Hypericum perforatum): an update on clinical observations.
St John's wort (SJW) extracts, prepared from the aerial parts of Hypericum perforatum, contain numerous pharmacologically active ingredients, including naphthodianthrones (e.g., hypericin and its derivatives), phloroglucinols derivatives (e.g., hyperforin, which inhibits the reuptake of a number of neurotransmitters, including serotonin), and flavonoids. Such extracts are widely used for the treatment of mild-to-moderate depression. As a monotherapy, SJW has an encouraging safety profile. However, relevant and, in some case, life-threatening interactions have been reported, particularly with drugs which are substrate of cytochrome P450 and/or P-glycoprotein. Well-documented SJW interactions include (1) reduced blood cyclosporin concentration, as suggested by multiple case reports as well as by clinical trials, (2) serotonin syndrome or lethargy when SJW was given with serotonin reuptake inhibitors, (3) unwanted pregnancies in women while using oral contraceptives and SJW, and (4) reduced plasma drug concentration of antiretroviral (e.g., indinavir, nevirapine) and anticancer (i.e., irinotecan, imatinib) drugs. Hyperforin, which is believed to contribute to the antidepressant action of St John's wort, is also strongly suspected to be responsible of most of the described interactions.


Is there an association between HIV-1 genital shedding and cervical intraepithelial neoplasia 2/3 among women on antiretroviral therapy?
Given the high prevalence of cervical intraepithelial neoplasia (CIN) grade 2/3 among HIV-infected women, we sought to examine the relationship between CIN 2/3 and HIV-1 genital shedding among women on highly active antiretroviral therapy (HAART). Paired plasma and cervical wick specimens for HIV-1 RNA measurements were obtained from 44 HIV-infected women with biopsy-confirmed CIN 2/3 (cases) and 44 age-matched HIV-infected women with normal cervical findings on colposcopy (controls). All subjects tested negative for sexually transmitted infections and had been stable on HAART for at least 3 months. HIV-1 viral load was measured in both blood and cervical specimens using commercial real-time polymerase chain reaction assays. Cervical intraepithelial neoplasia 2/3 was not significantly associated with the detection or magnitude of plasma or cervical HIV-1 RNA shedding. HIV was detected in the plasma in 10 cases (23%) and 10 controls (25%) (odds ratio = 1.0; 95% confidence interval = 0.33-3.1). Cervical HIV-1 was detected in 6 cases (13.6%) and 9 controls (20.4%) (odds ratio = 0.61; 95% confidence interval = 0.20-1.90). Mean HIV-1 concentration in cervical secretions among women with CIN 2/3 who shed was 2.93 log10 copies versus 2.72 among controls (p = .65). Among women on HAART, we found no relationship between CIN 2/3 and HIV-1 genital shedding.


Lymphovascular invasion in non-small-cell lung cancer: implications for staging and adjuvant therapy.
Lymphovascular space invasion (LVI) is an established negative prognostic factor and an indication for postoperative radiation therapy in many malignancies. The purpose of this study was to evaluate LVI in patients with early-stage non-small-cell lung cancer, undergoing surgical resection. All patients who underwent initial surgery for pT1-3N0-2 non-small-cell lung cancer at Duke University Medical Center from 1995 to 2008 were identified. A multivariate ordinal regression was used to assess the relationship between LVI and pathologic hilar and/or mediastinal lymph node (LN) involvement. A multivariate Cox regression analysis was used to evaluate the relationship of LVI and other clinical and pathologic factors on local failure (LF), freedom from distant metastasis (FFDM), and overall survival (OS). Kaplan-Meier methods were used to generate estimates of LF, FFDM, and OS in patients with and without LVI. One thousand five hundred and fifty-nine patients were identified. LVI was independently associated with the presence of regional LN involvement (p < 0.001) along with lobar (versus sublobar) resections (p < 0.001), and an open thoracotomy (versus video-assisted thoracoscopic surgery). LVI was not independently associated with LF on multivariate analysis (hazard ratio [HR] = 1.23, p = 0.25), but was associated with a lower FFDM (HR 1.52, p = 0.005) and OS (HR 1.26, p = 0.015). In addition, multivariate analysis showed that LVI was strongly associated with increased risk of developing distant metastases (HR = 1.75, p = 0.006) and death (HR = 1.53, p = 0.003) in adenocarcinomas but not in squamous carcinomas. LVI is associated with an increased risk of harboring regional LN involvement. LVI is also an adverse prognostic factor for the development of distant metastases and long-term survival.


Suspected yellow fever vaccine-associated viscerotropic adverse events (1973 and 1978), United States.
Two cases of yellow fever vaccine-associated viscerotropic adverse events (YEL-AVD) were identified by review of correspondence received at the Centers for Disease Control and Prevention (CDC; Ft. Collins, CO). The cases occurred in Indiana and Maryland in 1973 and 1978, respectively. One patient, a 75-year-old man with multi-organ failure died, and the other, a 31-year-old woman, was hospitalized for 14 days. Onset was 3-6 days after vaccination. The illness was characterized by fever, headache, myalgia, gastrointestinal symptoms, hepatic and renal dysfunction, and (in the fatal case), shock and coagulopathy, compatible with YEL-AVD. Liver pathology showed diffuse, spotty necrosis, acidophilic degeneration, Kupffer cell hyperplasia, and microvesicular fat. No virological confirmation was obtained, so that both cases remain classified as "suspect." The 1973 case is the earliest record of YEL-AVD; until now, the earliest known case of YEL-AVD had been in 1975 in Brazil, and most subsequent cases have been reported after 1995.


Commentary: Predicting aggression in youth.
Aggression in youth is common and encompasses a wide range of behaviors that vary along such dimensions as direction (toward self or others), degree of action (ideation, verbal threats, or actual assaults), degree of planning (reactive or impulsive, planned or predatory), system level (biological, psychological, or social), and seriousness of intent. Risk factors vary, depending on the range of behavior being predicted and the developmental level of the youth being assessed. The Brief Rating of Aggression by Children and Adolescents (BRACHA) shows promise for assessing the general risk of aggressiveness in a developmentally diverse child and adolescent inpatient population. Further research may show whether patterns of risk factors also have treatment and prognostic implications that will aid in working with this population.


End-of-life care in long-term care settings for older people: a literature review.
Most if not all of end-of-life care for people living in long-term care facilities is provided within the facility. This type of care is likely to increase with population ageing. This paper presents a literature review of the published literature on end-of-life care in long-term care facilities such as nursing homes, aged care facilities, residential care homes and continuing care settings, published between 2000 and 2004. A subset of literature that focuses on the development of practice and the identification of interventions to promote the provision of end-of-life care in care homes is examined in detail. Twenty-five papers are identified and these address modes of service delivery, the introduction of 'interventions' that facilitate care for individuals, and the development of tools. This work remains largely descriptive. Small-scale work dominates, reflecting the initial stages of knowledge development in this area of work. Suggestions for ways to expand the scope of the end-of-life care development work in long-term care settings are presented, as it is time to expand the horizons of these initiatives to become more rigorous and responsive to the needs of older people and their families in this care setting.


Changes in the Milk Metabolome of the Giant Panda (Ailuropoda melanoleuca) with Time after Birth--Three Phases in Early Lactation and Progressive Individual Differences.
Ursids (bears) in general, and giant pandas in particular, are highly altricial at birth. The components of bear milks and their changes with time may be uniquely adapted to nourish relatively immature neonates, protect them from pathogens, and support the maturation of neonatal digestive physiology. Serial milk samples collected from three giant pandas in early lactation were subjected to untargeted metabolite profiling and multivariate analysis. Changes in milk metabolites with time after birth were analysed by Principal Component Analysis, Hierarchical Cluster Analysis and further supported by Orthogonal Partial Least Square-Discriminant Analysis, revealing three phases of milk maturation: days 1-6 (Phase 1), days 7-20 (Phase 2), and beyond day 20 (Phase 3). While the compositions of Phase 1 milks were essentially indistinguishable among individuals, divergences emerged during the second week of lactation. OPLS regression analysis positioned against the growth rate of one cub tentatively inferred a correlation with changes in the abundance of a trisaccharide, isoglobotriose, previously observed to be a major oligosaccharide in ursid milks. Three artificial milk formulae used to feed giant panda cubs were also analysed, and were found to differ markedly in component content from natural panda milk. These findings have implications for the dependence of the ontogeny of all species of bears, and potentially other members of the Carnivora and beyond, on the complexity and sequential changes in maternal provision of micrometabolites in the immediate period after birth.


The risk of cardiovascular morbidity and cardiovascular mortality in systemic lupus erythematosus and lupus nephritis: a Danish nationwide population-based cohort study.
. To assess the role of LN as a risk factor for myocardial infarction (MI), stroke and cardiovascular mortality (CVM) in patients with SLE. . The study was conducted using individual-level data from multiple nationwide registers. We identified a cohort of patients diagnosed with SLE and further determined if they had a diagnosis of LN during 1995-2011. Each SLE patient was matched with five population controls. Hazard ratios (HRs) were calculated to measure the risk of MI, stroke and CVM in SLE patients relative to population controls and in SLE patients with relative to without LN. . We identified 1644 SLE patients with incident SLE; 233 of these patients had a diagnosis of incident LN during follow-up. The number of events in the SLE cohort was: 42 (MI), 74 (stroke) and 56 (CVM). For MI, the HR was 2.2 (95% CI: 1.4, 3.4) in SLE without LN and 18.3 (95% CI: 5.1, 65) in SLE with LN. The HR for LN was 8.5 (95% CI: 2.2, 33; P = 0.002). For stroke, HRs were 2.1 (95% CI: 1.5, 2.9) and 4.1 (95% CI: 1.9, 8.7) in SLE without and with LN, respectively, and we found no significant association with LN (P = 0.115). For CVM, the respective HRs were 1.6 (95% CI: 1.1, 2.4) and 7.8 (95% CI: 3.0, 20). The corresponding HR for LN was 4.9 (95% CI: 1.8, 13.7; P = 0.002). . The risk of MI and CVM, but not of stroke, is significantly higher in SLE patients with LN than SLE patients without LN.


Fluoride in drinking water and risk of hip fracture in the UK: a case-control study.
Although the benefits of water fluoridation for dental health are widely accepted, concerns remain about possible adverse effects, particularly effects on bone. Several investigators have suggested increased rates of hip fracture in places with high concentrations of fluoride in drinking water, but this finding has not been consistent, possibly because of unrecognised confounding effects. We did a case-control study of men and women aged 50 years and older from the English county of Cleveland, and compared patients with hip fracture with community controls. Current addresses were ascertained for all participants; for those who agreed to an interview and who passed a mental test, more detailed information was obtained about lifetime residential history and exposure to other known and suspected risk factors for hip fracture. Exposures to fluoride in water were estimated from the residential histories and from information provided by water suppliers. Analysis was by logistic regression. 914 cases and 1196 controls were identified, of whom 514 and 527, respectively, were interviewed. Among those interviewed, hip fracture was strongly associated with low body-mass index (p for trend <0.001) and physical inactivity (p for trend <0.001). Estimated average lifetime exposure to fluoride in drinking water ranged from 0.15 to 1.79 ppm. Current residence in Hartlepool was a good indicator for high lifetime exposure to fluoride. After adjustment for potential confounders, the odds ratio associated with an average lifetime exposure to fluoride > or =0.9 ppm was 1.0 [95% CI 0.7-1.5]. There is a low risk of hip fracture for people ingesting fluoride in drinking water at concentrations of about 1 ppm. This low risk should not be a reason for withholding fluoridation of water supplies.


Cardiovascular risk factors and cognitive performance in aging.
Atherosclerosis in cerebral blood vessels, especially those which compose the Circle of Willis, can lead to reduced supply of oxygen and nutrients to different cortical structures, affecting cognitive function. To analyze whether cardiovascular risk factors negatively influence cognitive performance in adults and elderly. One hundred twenty-nine participants of both sexes, aged over 50 years, without cognitive or functional impairment were included. Body mass index (BMI), hypertension (HTN), diabetes mellitus (DM), smoking history, plasma levels of total cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL) and very low density lipoproteins (VLDL) cholesterol, triglycerides, and glucose were the cardiovascular risk factors analyzed. Cognitive assessment was performed using tests of attention, working memory, category fluency and declarative memory. Controlling for age and education, multivariate linear regression models revealed that higher concentrations of triglycerides, as well as total, LDL and VLDL cholesterol, were associated with poorer performance on the digit span and category fluency tests. Higher HDL concentrations were associated with higher scores on category fluency tasks. Furthermore, higher BMI was associated with poorer delayed recall performance. The findings revealed that cardiovascular risk factors may negatively impact cognitive performance in aging.


Incomplete-Data Oriented Multiview Dimension Reduction via Sparse Low-Rank Representation.
For dimension reduction on multiview data, most of the previous studies implicitly take an assumption that all samples are completed in all views. Nevertheless, this assumption could often be violated in real applications due to the presence of noise, limited access to data, equipment malfunction, and so on. Most of the previous methods will cease to work when missing values in one or multiple views occur, thus an incomplete-data oriented dimension reduction becomes an important issue. To this end, we mathematically formulate the above-mentioned issue as sparse low-rank representation through multiview subspace (SRRS) learning to impute missing values, by jointly measuring intraview relations (via sparse low-rank representation) and interview relations (through common subspace representation). Moreover, by exploiting various subspace priors in the proposed SRRS formulation, we develop three novel dimension reduction methods for incomplete multiview data: 1) multiview subspace learning via graph embedding; 2) multiview subspace learning via structured sparsity; and 3) sparse multiview feature selection via rank minimization. For each of them, the objective function and the algorithm to solve the resulting optimization problem are elaborated, respectively. We perform extensive experiments to investigate their performance on three types of tasks including data recovery, clustering, and classification. Both two toy examples (i.e., Swiss roll and -curve) and four real-world data sets (i.e., face images, multisource news, multicamera activity, and multimodality neuroimaging data) are systematically tested. As demonstrated, our methods achieve the performance superior to that of the state-of-the-art comparable methods. Also, the results clearly show the advantage of integrating the sparsity and low-rankness over using each of them separately.


Cycad exposure and risk of dementia, MCI, and PDC in the Chamorro population of Guam.
To study cycad-derived products as possible risk factors for dementia, mild cognitive impairment (MCI), and parkinsonism-dementia complex (PDC) on Guam. Complete risk factor data from in-person interviews of 166 cases of Guam dementia, 50 cases of amnestic MCI, and 21 cases of PDC were compared with 1,581 controls in the base population regarding exposure to cycad-derived products from a traditional food (fadang), consumption of fruit bats, and use of cycad-derived topical medicine. Adjusted odds ratios (ORs) and 95% CIs for picking, processing, and eating fadang in young adulthood ranged from 1.42 (1.05 to 1.91) to 2.87 (1.48 to 5.56) and were consistently elevated and significant across all three diagnostic outcomes. Associations independent of exposure in young adulthood were for picking (OR 0.78, 95% CI 0.64 to 0.96) and processing (OR 0.77, 95% CI 0.63 to 0.94) fadang in childhood with Guam dementia. Men showed stronger and more consistent relations across exposure groups in young adulthood compared with women. No associations were found for consumption of fruit bats or exposure to cycad used as a topical medicine for any of the outcomes. Estimated adjusted population attributable risks suggest that exposure to eating fadang in young adulthood incurred the highest attributable risk percent. Environmental lifestyle and diet may contribute to the etiology of neurodegenerative diseases in the native population of Guam.


Baculovirus expression of the nucleoprotein gene of measles virus and utility of the recombinant protein in diagnostic enzyme immunoassays.
A recombinant baculovirus that expresses the nucleoprotein gene of measles virus (Edmonston vaccine strain) under the transcriptional control of the polyhedrin promoter was generated. The expressed protein (B-MVN) comigrated with the authentic viral nucleoprotein as observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it was phosphorylated. The B-MVN protein proved to be reactive with monoclonal antibodies in radioimmunoprecipitations, and it was immunogenic, eliciting in mice antisera that recognized the native nucleoprotein. In addition, the B-MVN protein was evaluated as a replacement source of antigen for whole virus in enzyme immunoassays (EIAs) for detection of measles virus-specific immunoglobulin M (IgM) and IgG antibodies. A capture IgM EIA with the B-MVN protein as antigen detected specific IgM antibodies in 18 (72%) acute- and all convalescent-phase specimens from 25 clinical measles cases and exceeded 99% specificity with 120 control specimens. An indirect IgG EIA with the B-MVN protein detected specific IgG antibodies in 129 of 131 (98%) serum specimens with antibodies to measles virus, and results obtained from testing 268 additional serum specimens were better correlated with measles virus-neutralizing antibodies than those obtained with a commercial EIA.


HIV drug resistance in sub-Saharan Africa: public health questions and the potential role of real-world data and mathematical modelling.
The prevalence of pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) is >10% in many low-income countries. As a consequence, several sub-Saharan African countries have implemented, or are considering the introduction of, non-NNRTI-based first-line antiretroviral therapy (ART) for treatment-naïve and treatment-experienced patients. This is occurring at a time when ART programmes are expanding, in response to the World Health Organization guidelines, which recommend ART initiation regardless of CD4 cell count. Both those developments raise important questions regarding their potential impact on HIV drug resistance and the impact of HIV drug resistance on clinical outcomes. Those issues are particularly relevant to sub-Saharan Africa, where standardised ART regimens are used and where viral load monitoring and resistance testing are often not done routinely. It is therefore essential to forecast the impact of the implementation of universal ART, and the introduction of drugs such as dolutegravir to first-line regimens, on HIV drug resistance in order to inform future policies and to help ensure sustainable positive long-term outcomes. We discuss important public health considerations regarding HIV drug resistance, and describe how mathematical modelling, combined with real-world data from the four African Regions of the International epidemiology Databases to Evaluate AIDS consortium, could provide an early warning system for HIV drug resistance in sub-Saharan Africa.


Peripartum hysterectomy in the UK: management and outcomes of the associated haemorrhage.
To identify women undergoing peripartum hysterectomy in the UK and to describe the causes, management and outcome of the associated haemorrhage. A population-based descriptive study using the UK Obstetric Surveillance System (UKOSS). All 229 hospitals with consultant-led maternity units in the UK. All women in the UK delivering between February 2005 and February 2006. Prospective case identification through the UKOSS monthly mailing. Rates with 95% CIs. Odds ratio estimates. Three hundred and eighteen women underwent peripartum hysterectomy. The most commonly reported causes of haemorrhage were uterine atony (53%) and morbidly adherent placenta (39%). Women were not universally managed with uterotonic therapies. Fifty women were unsuccessfully managed with B-Lynch or other brace suture prior to hysterectomy, 28 with activated factor VII and 9 with arterial embolisation. Twenty-one percent of women suffered damage to other structures, 20% required a further operation and 19% were reported to have additional severe morbidity. Bladder damage was more likely in women with placenta accreta (OR 3.41, 95% CI 1.55-7.48) than in women with uterine atony. There were no significant differences in outcomes between women undergoing total or subtotal hysterectomy. Two women died; case fatality 0.6% (95% CI 0-1.5%). For each woman who dies in the UK following peripartum hysterectomy, more than 150 survive. The associated haemorrhage is managed in a variety of ways and not universally according to existing guidelines. Further investigation of the outcomes following some of the more innovative therapies for control of haemorrhage is needed.


Solitary fibrous tumors arising in abdominal wall hernia sacs.
Solitary fibrous tumor (SFT) of the peritoneum is an unusual spindle-cell neoplasm. SFT was originally described in the pleura; however it is now diagnosed in multiple extrathoracic sites. Most believe that the tumor is of mesenchymal origin and should be classified as a variant of fibroma. SFT of the pleura and peritoneum have also been called fibrous mesothelioma, and the cell of origin is felt to be a pluripotential submesothelial mesenchymal cell. Primary tumors arising in hernia sacs are rare, and we report on two patients with hernia SFT. The first is a 67-year-old man who had a diffusely thickened distal left inguinal hernia sac. Within the sac was copious myxoid material mimicking pseudomyxoma peritonei. Herniorrhaphy and orchiectomy were performed. The second is a 44-year-old woman with a midepigastric mass attached to a ventral hernia. Wide local excision was performed. Both tumors demonstrated plump spindle cells, one with myxoid background and the other with keloidal collagen. Calretinin immunostaining was positive in both tumors, whereas CD34 was negative. This suggests tumor origin from a submesothial pluripotential cell that maintains potential for mesothelial differentiation. Surgical excision is the treatment of choice with the degree of resectability being a powerful predictor of outcome.


Efficient fringe image enhancement based on dual-tree complex wavelet transform.
In optical phase shift profilometry (PSP), parallel fringe patterns are projected onto an object and the deformed fringes are captured using a digital camera. It is of particular interest in real time three-dimensional (3D) modeling applications because it enables 3D reconstruction using just a few image captures. When using this approach in a real life environment, however, the noise in the captured images can greatly affect the quality of the reconstructed 3D model. In this paper, a new image enhancement algorithm based on the oriented two-dimenional dual-tree complex wavelet transform (DT-CWT) is proposed for denoising the captured fringe images. The proposed algorithm makes use of the special analytic property of DT-CWT to obtain a sparse representation of the fringe image. Based on the sparse representation, a new iterative regularization procedure is applied for enhancing the noisy fringe image. The new approach introduces an additional preprocessing step to improve the initial guess of the iterative algorithm. Compared with the traditional image enhancement techniques, the proposed algorithm achieves a further improvement of 7.2 dB on average in the signal-to-noise ratio (SNR). When applying the proposed algorithm to optical PSP, the new approach enables the reconstruction of 3D models with improved accuracy from 6 to 20 dB in the SNR over the traditional approaches if the fringe images are noisy.


Effect of anti-hypertensive drug dose frequency on the clinic-home blood pressure difference in patients with stage 1 treated hypertension.
Clinic blood pressure (CBP) is generally used for diagnosis and treatment monitoring in hypertension, but target organ damage correlates more closely with home blood pressure (HBP). Eliminating the clinic-home blood pressure difference (CHBPD) would make conventional CBP a more accurate alternative to HBP. This prospective, randomized, open trial compared the effect of a once-daily versus a twice-daily regimen of anti-hypertensive therapy on CHBPD. After a 2-week wash-out period, 85 confirmed stage 1 hypertensive patients were randomized to receive 2 mg trichlormethiazide daily in one (40 subjects) or two (45 subjects) daily doses for 3 weeks. CBP and HBP measurements were taken during the third week of treatment and the CHBPD calculated. After treatment, the systolic and diastolic CHBPD values were significantly greater in the once-daily regimen than in the twice-daily regimen. Conventional CBP should not be used as an alternative to HBP for evaluating prognosis and monitoring anti-hypertensive therapy when using a once-daily regimen.


Factors Associated With Loss of Usual Source of Care Among Older Adults.
Access to a usual source of care (USC) is associated with better preventive health and chronic disease treatment. Although most older adults have a USC, loss of USC, and factors associated with loss of USC, have not previously been examined. We followed 7,609 participants of the National Health and Aging Trends Study annually for up to 6 years (2011-2016). Discrete time-to-event techniques and pooled logistic regression were used to identify demographic, clinical, and social factors associated with loss of USC. Ninety-five percent of older adults reported having a USC in 2011, of whom 5% subsequently did not. Odds of losing a USC were higher among older adults with unmet transportation needs (adjusted odds ratio [aOR] 1.67), who moved to a new residence (aOR 2.08), and who reported depressive symptoms (aOR 1.40). Odds of losing a USC were lower for those who had ≥4 chronic conditions (vs 0-1; aOR 0.42) and with supplemental (aOR 0.52) or Medicaid (aOR 0.67) insurance coverage. We identified factors associated with older adults' loss of a USC. Potentially modifiable factors, such as access to transportation and supplemental insurance, deserve further investigation to potentially assist older adults with continuous access to care.


The impact of a breast cancer screening programme on quality-adjusted life-years.
Trials have shown that breast cancer screening is effective in reducing breast cancer mortality and gaining life-years. The question is whether taking into account the impact of a screening programme on quality of life would lead to a less positive view. Screening may have effects on quality of life in the short run for women participating and effects in the long run as a result of the expected shift in the number of women experiencing early and advanced phases of the disease, after the initiation of the programme. In this study 4 steps have been taken: (I) published studies on quality of life and breast cancer (screening) up to 1989 have been reviewed and summarized and, based on these data, the consequences of breast cancer and treatment have been described; (2) values have been assigned to the disease and treatment phases by experts in breast cancer and public health (N = 31, response 87%); (3) these values have been inserted in the MISCAN model predicting the prevalence of disease/treatment phases with and without a 2-yearly screening programme for women aged 50-70 and multiplied by the duration of these phases; (4) analyses have been done to establish the sensitivity of the results for the values inserted. The programme of 2-yearly mammographic screening for women aged 50-70 is predicted to be 8% "less effective" (range -19.7 to +3.2%) when computing quality-adjusted life-years. We conclude that this adjustment is too small to attribute a major role to quality of life in the decision to undertake a large-scale breast cancer screening programme.


Mice with the R176Q cardiac ryanodine receptor mutation exhibit catecholamine-induced ventricular tachycardia and cardiomyopathy.
Mutations in the cardiac ryanodine receptor 2 (RyR2) have been associated with catecholaminergic polymorphic ventricular tachycardia and a form of arrhythmogenic right ventricular dysplasia. To study the relationship between RyR2 function and these phenotypes, we developed knockin mice with the human disease-associated RyR2 mutation R176Q. Histologic analysis of hearts from RyR2(R176Q/+) mice revealed no evidence of fibrofatty infiltration or structural abnormalities characteristic of arrhythmogenic right ventricular dysplasia, but right ventricular end-diastolic volume was decreased in RyR2(R176Q/+) mice compared with controls, indicating subtle functional impairment due to the presence of a single mutant allele. Ventricular tachycardia (VT) was observed after caffeine and epinephrine injection in RyR2(R176Q/+), but not in WT, mice. Intracardiac electrophysiology studies with programmed stimulation also elicited VT in RyR2(R176Q/+) mice. Isoproterenol administration during programmed stimulation increased both the number and duration of VT episodes in RyR2(R176Q/+) mice, but not in controls. Isolated cardiomyocytes from RyR2(R176Q/+) mice exhibited a higher incidence of spontaneous Ca(2+) oscillations in the absence and presence of isoproterenol compared with controls. Our results suggest that the R176Q mutation in RyR2 predisposes the heart to catecholamine-induced oscillatory calcium-release events that trigger a calcium-dependent ventricular arrhythmia.


Uncovering the peptide-binding specificities of HLA-C: a general strategy to determine the specificity of any MHC class I molecule.
MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B molecules have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide library approach with a peptide-HLA-I dissociation assay, in this study we present a general strategy to determine the peptide-binding specificity of any MHC class I molecule. We applied this novel strategy to 17 of the most common HLA-C molecules, and for 16 of these we successfully generated matrices representing their peptide-binding motifs. The motifs prominently shared a conserved C-terminal primary anchor with hydrophobic amino acid residues, as well as one or more diverse primary and auxiliary anchors at P1, P2, P3, and/or P7. Matrices were used to generate a large panel of HLA-C-specific peptide-binding data and update our pan-specific NetMHCpan predictor, whose predictive performance was considerably improved with respect to peptide binding to HLA-C. The updated predictor was used to assess the specificities of HLA-C molecules, which were found to cover a more limited sequence space than HLA-A and -B molecules. Assessing the functional significance of these new tools, HLA-C*07:01 transgenic mice were immunized with stable HLA-C*07:01 binders; six of six tested stable peptide binders were immunogenic. Finally, we generated HLA-C tetramers and labeled human CD8(+) T cells and NK cells. These new resources should support future research on the biology of HLA-C molecules. The data are deposited at the Immune Epitope Database, and the updated NetMHCpan predictor is available at the Center for Biological Sequence Analysis and the Immune Epitope Database.


Dhaga Technique for Tissue Plane Preservation after Decompressive Craniectomy: Comparison of New Technique with Institutional Standard.
During cranioplasty after decompressive craniectomy, the temporalis muscle is firmly attached to the dural patch and intermixed with fibrotic tissue leading to considerable difficulty in dissecting the plane between the dura, galea and the temporalis muscle. This leads to increased surgical time, intraoperative blood loss, risk of complications and also affects rehabilitation. We have developed the "dhaga technique," which aids in preserving the plane between the muscle and dura in order to improve outcomes. Here we describe our technique and also compare the "dhaga technique" with the generally accepted standard procedure. A retrospective review was carried out of all patients undergoing cranioplasty following decompressive craniectomy either through the "dhaga technique" or the institutional standard (control group). Both techniques were compared using intra operative blood loss, duration of surgery and any complications as study variables. There were 133 patients were included in the study. The control group included 68 patients who underwent the procedure according to institutional standard, and 65 patients were included in the "dhaga technique group." Both groups were well matched for baseline characteristics. Patients in the "dhaga technique" group had statistically significant lower operating time (P value = 0.037) and intra operative blood loss (P value = 0.025). However, there was no significant difference in complications. The utilization of "dhaga technique" can potentially improve outcomes and reduce costs by decreasing operative time and blood loss. Moreover, the temporalis muscle preservation in the "dhaga technique" may also enhance aesthetic outcomes and chewing, which were not assessed in this study. There were no differences in complication between the two techniques.


Towards an understanding of speech and song perception.
The human singing voice plays an important role in music of all societies. It is an extremely flexible instrument and is capable of producing a tremendous range of sounds. As such, the human voice can be hard to classify and poses a major challenge for automatic audio discrimination and classification systems. Speech/song discrimination is an implicit goal of speech/music discrimination, where a division is sought between speech and song, such that the singing voice can be grouped together with other musical instruments in the same category. However, the division between speech and song is unclear and even human attempts at speech/song discrimination can be highly subjective and open to discussion. In this paper we present the results of a test that was designed to investigate differences in auditory perception for speech and song. Twenty-four subjects were instructed to attend to either the words or pitch, or both words and pitch of context-free spoken and sung phrases. After presentation of each phrase, subjects were asked to either type the words that they recalled, or select the correct pitch contour from a choice of four graphical representations, or do both, depending on the task specified before presentation of the phrase. The results of the experiment show a decrease in the amount of linguistic information retained by subjects for sung phrases and also a decrease in accuracy of response for the sung phrases when subjects attended to both words and pitch instead of words or pitch alone.


Spontaneous network activity <35 Hz accounts for variability in stimulus-induced gamma responses.
Gamma activity is thought to serve several cognitive processes, including attention and memory. Even for the simplest stimulus, the occurrence of gamma activity is highly variable, both within and between individuals. The sources of this variability, however, are largely unknown. In this paper, we address one possible cause: the cross-frequency influence of spontaneous, whole-brain network activity on visual stimulus processing. By applying Hidden Markov modelling to MEG data, we reveal that the trial-averaged gamma response to a moving grating depends on the individual network dynamics, inferred from slower brain activity (<35 Hz) in the absence of stimulation (resting-state and task baseline). In addition, we demonstrate that modulations of network activity in task baseline influence the gamma response on the level of trials. In summary, our results reveal a cross-frequency and cross-session association between gamma responses induced by visual stimulation and spontaneous network activity. These findings underline the dependency of visual stimulus processing on the individual, functional network architecture.


Number of MRI T1-hypointensity corrected by T2/FLAIR lesion volume indicates clinical severity in patients with multiple sclerosis.
Progressive brain atrophy, development of T1-hypointense areas, and T2-fluid-attenuated inversion recovery (FLAIR)-hyperintense lesion formation in multiple sclerosis (MS) are popular volumetric data that are often utilized as clinical outcomes. However, the exact clinical interpretation of these volumetric data has not yet been fully established. We enrolled 42 consecutive patients with MS who fulfilled the revised McDonald criteria of 2010. They were followed-up for more than 3 years from onset, and cross-sectional brain volumetry was performed. Patients with no brain lesions were excluded in advance from this study. For the brain volumetric data, we evaluated several parameters including age-adjusted gray-matter volume atrophy, age-adjusted white-matter volume atrophy, and T2-FLAIR lesion volume. The numbers of T1-hypointense and T2-FLAIR-hyperintense areas were also measured along the same timeline. The clinical data pertaining to disease duration, expanded disability status scale (EDSS), and MS severity score (MSSS) at the timing of volumetry were collected. Among the 42 patients with MS and brain lesions, the number of T1-hypointensity (rho = 0.51, p<0.001), gray-matter atrophy (rho = 0.40, p<0.01) and white-matter atrophy (rho = 0.49, p<0.001) correlated with the EDSS. T1-hypointensity count divided by FLAIR lesion volume correlated with the MSSS (rho = 0.60, p<0.001). Meanwhile, counts or volumes of FLAIR-hyperintense lesions were associated only with the times of past relapses, and did not correlate with present neurological disability level or ongoing disease activity. These findings were consistent regardless of the presence of spinal cord lesions. Numbers of T1-hypointensities and brain atrophy equally indicated the current neurological disability in MS. The number of T1-hypointensities divided by FLAIR lesion volume represented the clinical severity. The size or number of FLAIR lesions reflected earlier relapses but was not a good indicator of neurological disability or clinical severity.


Lung cancer in relation to environmental pollutants emitted from industrial sources.
A case-control study of residents who lived in the vicinity of a primary zinc smelter and a large steel manufacturing plant in eastern Pennsylvania was undertaken to investigate the role of environmental pollutants in the etiology of lung cancer. Lifetime residential, occupational, and smoking histories were obtained from the next of kin of 335 white male lung cancer cases and 332 white male controls. Soil samples were collected and analyzed for content in ppm of arsenic, copper, lead, manganese, zinc, and cadmium. Relative risks were determined according to distance of residence from the zinc smelter and the steel plant, and according to residence in areas with heavy and light levels of various pollutants. Two-fold risks for lung cancer were associated with residence near the zinc smelter and with residence in areas with heavy levels of arsenic and cadmium, although the number of individuals living in these higher risk areas was small. These increases were not explained by the effects of cigarette smoking or by employment in the zinc or steel industry. No excess risk was associated with living near the steel plant. The limited size of the study precludes causal interpretation, but the findings suggest the need for further investigation of metallic air pollution and lung cancer.


Development of lipoprotein-like lipid particles for drug targeting: neo-high density lipoproteins.
The possibility was explored of synthesizing, from commercially available lipids, high density lipoprotein (HDL)-like particles (neo-HDL) with the same physico-chemical and biological properties as native HDL. A preparation method involving egg yolk phosphatidylcholine, cholesterol, and apoproteins from HDL led to the formation of particles with a composition, size, electrophoretic mobility, and density similar to those of discoidal HDL. In vitro experiments with isolated parenchymal liver cells showed that unlabeled HDL and neo-HDL competed for the same high affinity binding sites as did radiolabeled neo-HDL, whereas an excess of unlabeled low density lipoprotein was ineffective. In vivo experiments with radio-labeled neo-HDL indicated that neo-HDL showed a slow decay upon injection into rats, whereas the liver uptake did not exceed > 10% of the injected dose. The small additional liver uptake of radioactivity from neo-HDL, compared with HDL, was due to enhanced uptake by endothelial and Kupffer cells. Lactosylation of neo-HDL led to a markedly increased decay rate and a rapid uptake by rat liver (80% in 10 min). Parenchymal cells accounted for > 90% of the total liver uptake of radiolabeled lactosylated neo-HDL. Because the liver uptake of lactosylated 125I-neo-HDL could be blocked by preinjection of N-acetylgalactosamine, we conclude that the asialoglycoprotein receptor, which is specifically localized on parenchymal liver cells, is responsible for the avid liver uptake. With a fibroblast cell line transfected with the human asialoglycoprotein receptor, it was found that lactosylated neo-HDL binds with high affinity (Kd, 40 nM), in a galactose-specific way. It can be concluded that, with commercially available lipid components, HDL-like particles (neo-HDL) with virtually the same characteristics as found for native apolipoprotein E-free HDL can be reconstituted. Lactosylated neo-HDL, which is rapidly taken up by galactose-specific receptors on parenchymal liver cells, might be used to transport antiviral drugs specifically to parenchymal liver cells.


How the center for Medicare and Medicaid innovation should test accountable care organizations.
The Patient Protection and Affordable Care Act establishes a national voluntary program for accountable care organizations (ACOs) by January 2012 under the auspices of the Centers for Medicare and Medicaid Services (CMS). The act also creates a Center for Medicare and Medicaid Innovation in the CMS. We propose that the CMS allow flexibility and tiers in ACOs based on their specific circumstances, such as the degree to which they are or are not fully integrated systems. Further, we propose that the CMS assume responsibility for ACO provisions and develop an ordered system for learning how to create and sustain ACOs. Key steps would include setting specific performance goals, developing skills and tools that facilitate change, establishing measurement and accountability mechanisms, and supporting leadership development.


Occupational exposure to sevoflurane following topical application to painful wounds.
Occupational exposure to halogenated anesthetics employed for general anesthesia has been extensively studied. Conversely, a new modality of treatment of painful wounds with topical sevoflurane lacks exposure studies. To evaluate the magnitude of acute occupational exposure to sevoflurane following topical application to painful wounds. Four patients with chronic painful wounds were treated with topical sevoflurane (20, 20, 20 and 10 mL) following an approved therapeutic protocol in our Pain Management Unit. Eight passive dosimeters were placed at different locations of a treatment room with a volume of 163 m3 and 3.3 air changes per hour: 3 for near peak (for 20-50 min) and 1 overall exposure (for 3.4 h) at the nurse's breathing zone, and 4 for area exposure (for 3-3.4 h). Worst-case scenario theoretical concentrations of sevoflurane were also calculated. The highest levels were obtained for two dosimeters worn by the nurse at the breathing zone (8.28 and 9.12 ppm-TWA [parts per million-Time-Weighted Average]), while the lowest level was obtained from the dosimeter placed on the most distant wall from patients (0.73 ppm-TWA). Theoretical concentrations were calculated from standard volatilization principles and were in agreement with the concentrations measured. Discussion-Conclusions: All air concentrations measured were lower than exposure limits set by occupational safety agencies from Finland, Sweden and Norway, which range from 10 ppm for a TWA of 8 hours to 20 ppm for short-term exposures (15 min). Application of topical sevoflurane on wounds seems to be environmentally safe for health-care professionals as it produces exposure levels lower than the established limits for anesthetic procedures.


Dural stimulation in rats causes brain-derived neurotrophic factor-dependent priming to subthreshold stimuli including a migraine trigger.
Migraine is one of the most common and most disabling disorders. Between attacks, migraine patients are otherwise normal but are sensitized to nonnoxious events known as triggers. The purpose of these studies was to investigate whether a headache-like event causes sensitization, or priming, to subsequent subthreshold events. Interleukin-6 (IL-6) was applied to the rat cranial dura mater which produced cutaneous facial and hind paw allodynia that lasted 24 hours. At 72 hours, IL-6-treated rats developed allodynia in response to dural stimulation with either a pH 6.8 or pH 7.0 solution and to a systemic nitric oxide (NO) donor, a well-known migraine trigger. Vehicle-treated rats did not respond to either pH stimulus or to the NO donor, demonstrating that IL-6 exposure primes rats to subthreshold stimuli. Inhibitors of brain-derived neurotrophic factor (BDNF) signaling given either systemically or intracisternally 24 hours after IL-6 eliminated responses to dural pH stimulation at 72 hours. Additionally, intracisternal administration of BDNF without previous dural stimulation produced allodynia and once resolved, animals were primed to dural pH 6.8/pH 7.0 and a systemic NO donor. Finally, hind paw IL-6 produced paw allodynia but not priming to paw injection of pH 7.0 at 72 hours demonstrating differences in priming depending on location. These data indicate that afferent input from the meninges produces BDNF-dependent priming of the dural nociceptive system. This primed state mimics the interictal period of migraine where attacks can be triggered by normally nonnoxious events and suggests that BDNF-dependent plasticity may contribute to migraine.


Pre-Capture Privacy for Small Vision Sensors.
The next wave of micro and nano devices will create a world with trillions of small networked cameras. This will lead to increased concerns about privacy and security. Most privacy preserving algorithms for computer vision are applied after image/video data has been captured. We propose to use privacy preserving optics that filter or block sensitive information directly from the incident light-field before sensor measurements are made, adding a new layer of privacy. In addition to balancing the privacy and utility of the captured data, we address trade-offs unique to miniature vision sensors, such as achieving high-quality field-of-view and resolution within the constraints of mass and volume. Our privacy preserving optics enable applications such as depth sensing, full-body motion tracking, people counting, blob detection and privacy preserving face recognition. While we demonstrate applications on macro-scale devices (smartphones, webcams, etc.) our theory has impact for smaller devices.


Relative Importance of Different Water Categories as Sources of N-Nitrosamine Precursors.
A comparison of loadings of N-nitrosamines and their precursors from different source water categories is needed to design effective source water blending strategies. Previous research using Formation Potential (FP) chloramination protocols (high dose and prolonged contact times) raised concerns about precursor loadings from various source water categories, but differences in the protocols employed rendered comparisons difficult. In this study, we applied Uniform Formation Condition (UFC) chloramination and ozonation protocols mimicking typical disinfection practice to compare loadings of ambient specific and total N-nitrosamines as well as chloramine-reactive and ozone-reactive precursors in 47 samples, including 6 pristine headwaters, 16 eutrophic waters, 4 agricultural runoff samples, 9 stormwater runoff samples, and 12 municipal wastewater effluents. N-Nitrosodimethylamine (NDMA) formation from UFC and FP chloramination protocols did not correlate, with NDMA FP often being significant in samples where no NDMA formed under UFC conditions. N-Nitrosamines and their precursors were negligible in pristine headwaters. Conventional, and to a lesser degree, nutrient removal wastewater effluents were the dominant source of NDMA and its chloramine- and ozone-reactive precursors. While wastewater effluents were dominant sources of TONO and their precursors, algal blooms, and to a lesser degree agricultural or stormwater runoff, could be important where they affect a major fraction of the water supply.


Antigen diversity in the parasitic bacterium Anaplasma phagocytophilum arises from selectively-represented, spatially clustered functional pseudogenes.
Anaplasma phagocytophilum is a tick-transmitted bacterial pathogen of humans and other animals, and is an obligate intracellular parasite. Throughout the course of infection, hosts acquire temporary resistance to granulocytic anaplasmosis as they develop immunity specific for the major antigen, major surface protein 2 (Msp2). However, the bacterium then utilizes a novel recombination mechanism shuffling functional pseudogenes sequentially into an expression cassette with conserved 5' and 3' ends, bypassing host immunity. Approximately 100 pseudogenes are present in the only fully sequenced human-origin HZ genome, representing the possibility for almost unlimited antigenic diversity. In the present study, we identified a select group of 20% of the A. phagocytophilum HZ msp2 pseudogenes that have matched preferentially to human, canine, and equine expression cassettes. Pseudogenes cluster predominantly in one spatial run limited to a single genomic island in less than 50% of the genome but phylogenetically related pseudogenes are neither necessarily located in close proximity on the genome nor share similar percent identity with expression cassettes. Pseudogenes near the expression cassette (and the origin) are more likely to be expressed than those farther away. Taken together, these findings suggest that there may be natural selection pressure to retain pseudogenes in one cluster near the putative origin of replication, even though global recombination shuffles pseudogenes around the genome, separating pseudogenes that share genetic origins as well as those with similar identities.


A possible relativistic jetted outburst from a massive black hole fed by a tidally disrupted star.
Gas accretion onto some massive black holes (MBHs) at the centers of galaxies actively powers luminous emission, but most MBHs are considered dormant. Occasionally, a star passing too near an MBH is torn apart by gravitational forces, leading to a bright tidal disruption flare (TDF). Although the high-energy transient Sw 1644+57 initially displayed none of the theoretically anticipated (nor previously observed) TDF characteristics, we show that observations suggest a sudden accretion event onto a central MBH of mass about 10(6) to 10(7) solar masses. There is evidence for a mildly relativistic outflow, jet collimation, and a spectrum characterized by synchrotron and inverse Compton processes; this leads to a natural analogy of Sw 1644+57 to a temporary smaller-scale blazar.


The evolution of RecD outside of the RecBCD complex.
The common understanding of the function of RecD, as derived predominantly from studies in Escherichia coli, is that RecD is one of three enzymes in the RecBCD double-stranded break repair DNA recombination complex. However, comparative genomics has revealed that many organisms possess a recD gene even though the other members of the complex, recB and recC, are not present. Further, bioinformatic analyses have shown that there is substantial sequence dissimilarity between recD genes associated with recB and recC (recD1), and those that are not associated with recBC (recD2). Deinococcus radiodurans, known for its extraordinary DNA repair capability, is one such organism that does not possess either recB or recC, and yet does possess a recD gene. The recD of D. radiodurans was deleted and this mutant was shown to have a capacity to repair double-stranded DNA breaks equivalent to wild-type. The phylogenetic history of recD was studied using a dataset of 120 recD genes from 91 fully sequenced species. The analysis focused upon the role of gene duplication and functional genomic context in the evolution of recD2, which appears to have undergone numerous independent events resulting in duplicate recD2 genes. The role of RecD as part of the RecBCD complex appears to have a divergence from an earlier ancestral RecD function still preserved in many species including D. radiodurans.


CIDP presenting as recurrent severe back pain without weakness or sensory loss.
A 71-year-old woman presented with severe back pain, limb weakness and cranial nerve dysfunction associated with high cerebrospinal fluid (CSF) protein; we diagnosed Guillain-Barré syndrome and her symptoms completely resolved after intravenous immunoglobulin. Over the next 4 years, she had three further episodes of excruciating back pain accompanied by raised CSF protein, but without weakness, sensory loss, or abnormalities in routine nerve conduction studies. Sensory evoked potentials suggested proximal demyelination and lumbosacral plexus imaging suggested inflammation. We argue that this is a relapsing proximal polyradiculoneuropathy on the spectrum of chronic inflammatory demyelinating polyradiculoneuropathy.


Predictors of urinary continence following tethered cord release in children with occult spinal dysraphism.
Children with occult spinal dysraphism represent a wide spectrum of patients. Previous studies assessing urologic outcomes have in part been deficient due to the inability to appropriately categorize these patients and gather long-term follow-up data. In this study, a uniform set of patients that had occult spinal dysraphism with magnetic resonance imaging findings of a fatty filum terminale (FF) and/or low-lying cord (LLC) was identified. Utilizing long-term follow-up data, predictors for achieving urinary continence following tethered cord release (TCR) were determined. A retrospective chart review of pediatric patients with a diagnosis of tethered cord who underwent TCR from 1995 to 2005 was performed. Analysis was limited to patients who had primary TCR by one of two neurosurgeons within our multidisciplinary spina bifida clinic, who had greater than 1-year follow-up, and who were old enough to have continence status assessed (age > 6 years unless definitively toilet trained earlier). Patients with other associated forms of spinal dysraphism (lipomyelomeningeocele, spinal lipomas, sacral agenesis), anorectal malformations, and genitourinary anomalies were excluded. Pre- and post-TCR urodynamics, radiographic studies, functional orthopedic status, and urologic outcomes were assessed. Urodynamic results were categorized by three blinded urologists into one of three urodynamic patterns: (1) normal, (2) indeterminate, and (3) high risk. A total of 147 patients with FF and/or LLC that underwent TCR were reviewed. 51 patients were excluded because of another associated spinal dysraphism (15/51 patients) or an anorectal/genitourinary anomaly (36/51 patients). Fifty-nine of the remaining 96 patients had adequate long-term follow-up data to be included in the study. 20 patients were asymptomatic at the time of TCR while 39 presented with orthopedic and/or urologic symptoms. The average age at surgery was 59.3 months (range 2-277 months) with an average follow-up of 7.0 years (range 1-16 years). At latest follow-up, 47 (80%) patients were continent while 12 (20%) were either incontinent or utilizing clean intermittent catheterization (CIC). Statistical analysis revealed that age of untethering, type of cutaneous lesion, level of conus, presence of hydronephrosis, and high-grade vesicoureteral reflux (VUR) were not independent predictors of continence. In patients with a cutaneous lesion who were asymptomatic, 19/20 obtained continence post-TCR (*p = 0.036). In patients who were old enough to assess continence pre-TCR, 14/25 patients were continent pre-TCR and 11/25 were incontinent. Of the 14 who were continent pre-TCR, all remained continent post-TCR (*p = 0.002). Of the 11 who were incontinent pre-TCR, five (45%) eventually became continent post-TCR. Assessment of urodynamic data revealed that neither pre- nor post-TCR urodynamics predicted continence status. Isolated cutaneous lesions and preoperative continence status are positive predictors for post-TCR continence. While pre- and post-TCR urodynamics do not predict continence status, their utility in preoperative work-up, monitoring for retethering, and long-term urologic follow-up requires further examination.


Complement protein C1q and adiponectin stimulate Mer tyrosine kinase-dependent engulfment of apoptotic cells through a shared pathway.
The failure to clear apoptotic cells is linked to defects in development and autoimmunity. Complement component C1q is required for efficient engulfment of apoptotic cells (efferocytosis), and C1q deficiency leads to the development of lupus. We recently identified a novel molecular mechanism for C1q-dependent efferocytosis in murine macrophages. C1q elicited the expression of Mer tyrosine kinase (Mer), a receptor that regulates efficient efferocytosis and prevention of autoimmunity. To characterize the C1q-dependent signal transduction mechanism, pathway analysis of the transcriptome from C1q-activated macrophages was performed, and it identified the adiponectin signaling pathway as significantly upregulated with C1q. Adiponectin is structurally homologous to C1q and regulates cellular metabolism via downstream activation of 5'adenosine monophosphate-activated protein kinase (AMPK). Macrophage stimulation with C1q resulted in the activation of AMPK, and silencing of AMPK expression using siRNA-inhibited C1q-dependent efferocytosis. Adiponectin signaling also stimulates activation of nuclear receptors, and inhibition of the nuclear receptor retinoid X receptor abrogated C1q-dependent Mer expression and efferocytosis. Furthermore, adiponectin elicited Mer expression and Mer-dependent efferocytosis in macrophages similar to cells stimulated with C1q. Collectively, our results suggest that C1q and adiponectin share a common signal transduction cascade to promote clearance of apoptotic cells, and identify a novel molecular pathway required for efficient efferocytosis.


Anisakid nematodes from stranded pygmy sperm whales, Kogia breviceps (Kogiidae), in three localities of the Yucatan Peninsula, Mexico.
The present paper reports the presence of 3 adult and juvenile anisakid nematode species: Anisakis simplex, A. brevispiculata, and Pseudoterranova ceticola, which were recovered from the digestive tract of stranded pygmy sperm whales (Kogia breviceps) from 3 localities along the coast of the Yucatan Peninsula. The presence of these anisakid adult nematodes suggests that larval stages may occur in cephalopods or fishes used for human consumption, which represents a potential danger to public health. The occurrence of the 3 anisakid species in coastal waters of the Yucatan Peninsula represents new geographical records for Mexico.


Efficient computation and visualization of coherent structures in fluid flow applications.
The recently introduced notion of Finite-Time Lyapunov Exponent to characterize Coherent Lagrangian Structures provides a powerful framework for the visualization and analysis of complex technical flows. Its definition is simple and intuitive, and it has a deep theoretical foundation. While the application of this approach seems straightforward in theory, the associated computational cost is essentially prohibitive. Due to the Lagrangian nature of this technique, a huge number of particle paths must be computed to fill the space-time flow domain. In this paper, we propose a novel scheme for the adaptive computation of FTLE fields in two and three dimensions that significantly reduces the number of required particle paths. Furthermore, for three-dimensional flows, we show on several examples that meaningful results can be obtained by restricting the analysis to a well-chosen plane intersecting the flow domain. Finally, we examine some of the visualization aspects of FTLE-based methods and introduce several new variations that help in the analysis of specific aspects of a flow.


Speaking through diabetes: Rethinking the significance of lay discourses on diabetes.
The disproportionate prevalence of Type II diabetes mellitus among the poor suggests that, in addition to lifestyle factors, social suffering may be embodied in diabetes. In this article, we examine the role of social distress in narratives collected from 26 Mexican Americans seeking diabetes care at a public hospital in Chicago. By linking social suffering with diabetes causality, we argue that our participants use diabetes much like an "idiom of distress," leveraging somatic symptoms to disclose psychological distress. We argue that diabetes figures both as an expression and a product of social suffering in these narratives. We propose that increasingly prevalent chronic diseases, like diabetes, which are closely associated with social disparities in health, may function as idioms for psychological and social suffering. Such findings inform the anthropological literature and emerging clinical and scientific discourse about the roles of stress and psychological distress in diabetes experiences among underserved groups.


Bidirectional associations of vision and hearing loss with anxiety: prospective findings from the Three-City Study.
the aim of this study was to examine the bidirectional association of vision loss (VL) and hearing loss (HL) with anxiety over a 12-year period. this was a prospective population-based study. community-dwelling French adults. the study included 3,928 adults aged 65 and above from the Three-City study. the relationships of VL, as assessed by near visual acuity and self-reported HL to a diagnosis of generalised anxiety disorder (GAD) were assessed over 12 years. A further objective was to explore whether sensory loss has a differential relationship with GAD than with anxiety symptoms, assessed by the Spielberger's State-Trait Anxiety Inventory. at baseline, HL [odds ratio (OR) = 1.41, 95% confidence interval (CI) 1.02-1.96, P = 0.04], but not mild or moderate to severe VL, was associated with self-reported anxiety symptoms (OR = 1.07 95% CI 0.63-1.83, P = 0.80; OR = 0.66 95% CI 0.12-2.22, P = 0.50, respectively). Neither vision nor HL was significantly associated with incident GAD. Baseline GAD was related to increased risk of incident HL (OR = 1.17, 95% CI 1.07-1.28, P < 0.001), but not mild or moderate to severe vision loss (OR = 1.01, 95% CI 0.96-1.06, P = 0.81; OR = 0.97, 95% CI 0.89-1.05, P = 0.45, respectively). increased anxiety symptoms were observed in older adults with HL, whereas we found no evidence for an association between VL and anxiety. Anxiety was prospectively associated with increased risk of reporting HL. Improved detection of anxiety in older adults with HL may improve quality of life.


Mechanical analysis of ovine and pediatric pulmonary artery for heart valve stent design.
Transcatheter heart valve replacement is an attractive and promising technique for congenital as well as acquired heart valve disease. In this procedure, the replacement valve is mounted in a stent that is expanded at the aimed valve position and fixated by clamping. However, for this technique to be appropriate for pediatric patients, the material properties of the host tissue need to be determined to design stents that can be optimized for this particular application. In this study we performed equibiaxial tensile tests on four adult ovine pulmonary artery walls and compared the outcomes with one pediatric pulmonary artery. Results show that the pediatric pulmonary artery was significantly thinner (1.06 ± 0.36 mm (mean ± SD)) than ovine tissue (2.85 ± 0.40 mm), considerably stiffer for strain values that exceed the physiological conditions (beyond 50% strain in the circumferential and 60% in the longitudinal direction), more anisotropic (with a significant difference in stiffness between the longitudinal and circumferential directions beyond 60% strain) and presented stronger non-linear stress-strain behavior at equivalent strains (beyond 26% strain) compared to ovine tissue. These discrepancies suggest that stents validated and optimized using the ovine pre-clinical model might not perform satisfactorily in pediatric patients. The material parameters derived from this study may be used to develop stent designs for both applications using computational models.


Normalisation method can affect gluteus medius electromyography results during weight bearing exercises in people with hip osteoarthritis (OA): a case control study.
Surface electromyography (sEMG) is used to assess muscle activation during therapeutic exercise, but data are significantly affected by inter-individual variability and requires normalisation of the sEMG signal to enable comparison between individuals. The purpose of this study was to compare two normalisation methods, a maximal method (maximum voluntary isometric contraction (MVIC)) and non-maximal peak dynamic method (PDM), on gluteus medius (GMed) activation using sEMG during three weight-bearing exercises in people with hip osteoarthritis (OA) and healthy controls. Thirteen people with hip OA and 20 controls performed three exercises (Squat, Step-Up, Step-Down). Average root-mean squared EMG amplitude based on MVIC and PDM normalisation was compared between groups for both involved and uninvolved hips using Mann-Whitney tests. Using MVIC normalisation, significantly higher normalised GMed EMG amplitudes were found in the OA group during all Step-up and down exercises on the involved side (p=0.02-0.001) and most of the Step exercises on the uninvolved side (p=0.03-0.04), but not the Squat (p>0.05), compared to controls. Using PDM normalisation, significant between-group differences occurred only for Ascending Squat (p=0.03) on the involved side. MVIC normalisation demonstrated higher inter-trial relative reliability (ICCs=0.78-0.99) than PDM (ICCs=0.37-0.84), but poorer absolute reliability using Standard Error of Measurement. Normalisation method can significantly affect interpretation of EMG amplitudes. Although MVIC-normalised amplitudes were more sensitive to differences between groups, there was greater variability using this method, which raises concerns regarding validity. Interpretation of EMG data is strongly influenced by the normalisation method used, and this should be considered when applying EMG results to clinical populations.


Psychophysiologic treatment for patients with medically unexplained symptoms: a randomized controlled trial.
Patients presenting with medically unexplained physical symptoms (MUPS) typically present with significant distress and marked impairment in functioning and pose a unique challenge to health care providers. The purpose of this study was to examine the efficacy of a psychophysiological treatment (PT) for MUPS. Thirty-eight participants meeting criteria for subthreshold somatization disorder (abridged somatization) were randomly assigned to one of two conditions: (1) standard medical care augmented by a psychiatric consultation intervention (wait-list) or (2) a 10-session, manualized, individually-administered PT added to the psychiatric consultation intervention. Assessments were conducted at baseline, at midpoint (after four sessions), and after completing the last session. The primary outcome measure was the severity scale of the Clinical Global Impression Scale anchored for Somatic Symptoms (CGI-SD). Secondary outcome measures were responder status as determined by clinical ratings, self-report measures of mental and physical functioning. At the end of the trial, the severity (and frequency) of physical symptoms improved significantly more (p<0.05) in the intervention group. The average improvement in the CGI-SD was 0.80 points greater in the intervention group than in the wait-list group. PT was also associated with greater improvements in self-reported functioning and depressive symptomatology. The effect sizes at the final assessment point indicate that this intervention had a robust effect on complex somatic symptom presentations. For patients with high levels of MUPS (abridged somatization), PT produces significant improvements in symptoms and functional status.