H19-DMR allele-specific methylation analysis reveals epigenetic heterogeneity of CTCF binding site 6 but not of site 5 in head-and-neck carcinomas: A pilot case-control analysis

Aberrant methylation of seven potential binding sites of the CTCF factor in the differentially methylated region upstream of the H19 gene (H19-DMR) has been suggested as critical for the regulation of IGF2 and H19 imprinted genes. In this study, we analyzed the allele-specific methylation pattern of CTCF binding sites 5 and 6 using methylationsensitive restriction enzyme PCR followed by RFLP analysis in matched tumoral and lymphocyte DNA from head-and-neck squamous cell carcinoma (HNSCC) patients, as well as in lymphocyte DNA from control individuals who were cancer-free. The monoallelic methylation pattern was maintained in CTCF binding site 5 in 22 heterozygous out of 91 samples analyzed. Nevertheless, a biallelic methylation pattern was detected in CTCF binding site 6 in a subgroup of HNSCC patients as a somatic acquired feature of tumor cells. An atypical biallelic methylation was also observed in both tumor and lymphocyte DNA from two patients, and at a high frequency in the control group (29 out of 64 informative controls). Additionally, we found that the C/T transition detected by HhaI RFLP suppressed one dinucleotide CpG in critical CTCF binding site 6, of a mutation showing polymorphic frequencies. Although a heterogeneous methylation pattern was observed after DNA sequencing modified by sodium bisulfite, the biallelic methylation pattern was confirmed in 9 out of 10 HNSCCs. These findings are likely to be relevant in the epigenetic regulation of the DMR, especially in pathological conditions in which the imprinting of IGF2 and H19 genes is disrupted.

Loss of Y-chromosome does not correlate with age at onset of head and neck carcinoma: a case-control study

Loss of Y-chromosome has been correlated with older age in males. Furthermore, current evidence indicates that Y-chromosome loss also occurs in several human tumors, including head and neck carcinomas. However, the association between Y nullisomy and the occurrence of neoplasias in elderly men has not been well established. In the present study, the association between Y-chromosome loss and head and neck carcinomas was evaluated by comparison to cells from peripheral blood lymphocytes and normal mucosa of cancer-free individuals matched for age using dual-color fluorescence in situ hybridization. Twenty-one patients ranging in age from 28 to 68 years were divided into five-year groups for comparison with 16 cancer-free individuals matched for age. The medical records of all patients were examined to obtain clinical and histopathological data. None of the patients had undergone radiotherapy or chemotherapy before surgery. In all groups, the frequency of Y-chromosome loss was higher among patients than among normal reference subjects (P < 0.0001) and was not age-dependent. These data suggest that Y-chromosome loss is a tumor-specific alteration not associated with advanced age in head and neck carcinomas.

Linear parameter varying control design for rotating systems supported by journal bearings

Linear parameter varying (LPV) control is a model-based control technique that takes into account time-varying parameters of the plant. In the case of rotating systems supported by lubricated bearings, the dynamic characteristics of the bearings change in time as a function of the rotating speed. Hence, LPV control can tackle the problem of run-up and run-down operational conditions when dynamic characteristics of the rotating system change significantly in time due to the bearings and high vibration levels occur. In this work, the LPV control design for a flexible shaft supported by plain journal bearings is presented. The model used in the LPV control design is updated from unbalance response experimental results and dynamic coefficients for the entire range of rotating speeds are obtained by numerical optimization. Experimental implementation of the designed LPV control resulted in strong reduction of vibration amplitudes when crossing the critical speed, without affecting system behavior in sub- or supercritical speeds. (C) 2012 Elsevier Ltd. All rights reserved.

Differentiation of African Components of Ancestry to Stratify Groups in a Case-Control Study of a Brazilian Urban Population

Background: Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. Methods: We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. Results: One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA <0.25 and >0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA <0.25. These individuals presented a high probability of Native American and East Asian ancestral components; however, no individuals originally giving these self-described ancestries were observed in this study. Conclusions: The strategy proposed for the assessment of ancestry and adjustment of case and control groups for an association study is an important step for the proper construction of the study, particularly when subjects are taken from a complex urban population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.

Factors associated with maternal intrapartum transfers from a freestanding birth centre in Sao Paulo, Brazil: A case control study

Objectives: to identify factors associated with maternal intrapartum transfer from a freestanding birth centre to hospital. Design: case-control study with retrospective data collection. Participants and settings: cases included all 111 women transferred from a freestanding birth centre in Sao Paulo to the referral hospital, from March 2002 to December 2009. The controls were 456 women who gave birth in the birth centre during the same period who were not transferred, randomly selected with four controls for each case. Methods: data were obtained from maternal records. Factors associated with maternal intrapartum transfers were initially analysed using a chi(2) test of association. Variables with p < 0.20 were then included in multivariate analyses. A multiple logistic regression model was built using stepwise forward selection; variables which reached statistical significance at p < 0.05 were considered to be independently associated with maternal transfer. Findings: during the study data collection period, 111(4%) of 2,736 women admitted to the centre were transferred intrapartum. Variables identified as independently associated factors for intrapartum transfer included nulliparity (OR 5.1, 95% CI 2.7-9.8), maternal age >= 35 years (OR 5.4, 95% CI 2.1-13.4), not having a partner (OR 2.8, 95% CI 1.5-5.3), cervical dilation <= 3 cm on admission to the birth centre (OR 1.9, 95% CI 1.1-3.2) and between 5 and 12 antenatal appointments at the birth centre (OR 3.8, 95% CI 1.9-7.5). In contrast, a low correlation between fundal height and pregnancy gestation (OR 0.3, 95% CI 0.2-0.6) appeared to be protective against transfer. Conclusions and implications for practice: identifying factors associated with maternal intrapartum transfer could support decision making by women considering options for place of birth, and support the content of appropriate information about criteria for admission to a birth centre. Findings add to the evidence base to support identification of women in early labour who may experience later complications and could support timely implementation of appropriate interventions associated with reducing transfer rates. (C) 2012 Elsevier Ltd. All rights reserved.

Nerve fiber layer in glaucomatous hemifield loss: a case-control study with time- and spectral-domain optical coherence tomography

Purpose: To evaluate the retinal nerve fiber layer measurements with time-domain (TD) and spectral-domain (SD) optical coherence tomography (OCT), and to test the diagnostic ability of both technologies in glaucomatous patients with asymmetric visual hemifield loss. Methods: 36 patients with primary open-angle glaucoma with visual field loss in one hemifield (affected) and absent loss in the other (non-affected), and 36 age-matched healthy controls had the study eye imaged with Stratus-OCT (Carl Zeiss Meditec Inc., Dublin, California, USA) and 3 D OCT-1000 (Topcon, Tokyo, Japan). Peripapillary retinal nerve fiber layer measurements and normative classification were recorded. Total deviation values were averaged in each hemifield (hemifield mean deviation) for each subject. Visual field and retinal nerve fiber layer "asymmetry indexes" were calculated as the ratio between affected versus non-affected hemifields and corresponding hemiretinas. Results: Retinal nerve fiber layer measurements in non-affected hemifields (mean [SD] 87.0 [17.1] mu m and 84.3 [20.2] mu m, for TD and SD-OCT, respectively) were thinner than in controls (119.0 [12.2] mu m and 117.0 [17.7] mu m, P<0.001). The optical coherence tomography normative database classified 42% and 67% of hemiretinas corresponding to non-affected hemifields as abnormal in TD and SD-OCT, respectively (P=0.01). Retinal nerve fiber layer measurements were consistently thicker with TD compared to SD-OCT. Retinal nerve fiber layer thickness asymmetry index was similar in TD (0.76 [0.17]) and SD-OCT (0.79 [0.12]) and significantly greater than the visual field asymmetry index (0.36 [0.20], P<0.001). Conclusions: Normal hemifields of glaucoma patients had thinner retinal nerve fiber layer than healthy eyes, as measured by TD and SD-OCT. Retinal nerve fiber layer measurements were thicker with TD than SD-OCT. SD-OCT detected abnormal retinal nerve fiber layer thickness more often than TD-OCT.

Effectiveness of the polysaccharide pneumococcal vaccine among HIV-infected persons in Brazil: a case control study

Abstract Background Polysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population. The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil. Methods A case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview. Results After adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI: <0 to 62%). Conclusion We were unable to demonstrate a statistically significant protective effect of 23 valent polysaccharide against invasive pneumococcal infection vaccine among HIV-infected adults in Brazil. While the vaccine is relatively inexpensive and safe, its effectiveness among HIV-infected adults in Brazil is uncertain.

Risk factors associated with death in Brazilian children with severe dengue: a case-control study

Objective: The purpose of this case-control study was to evaluate risk factors associated with death in children with severe dengue. Methods: The clinical condition of hospitalized patients with severe dengue who died (cases, n = 18) was compared with that of hospitalized patients with severe dengue who survived (controls, n = 77). The inclusion criteria for this study were age under 13 years; hospital admission in São Luis, northeastern Brazil; and laboratory-confirmed diagnosis of dengue. Results: Severe bleeding (hemoptysis), a defining criterion for dengue severity, was the factor most strongly associated with death in our study. We also found that epistaxis and persistent vomiting, both included as warning signs in the World Health Organization (WHO) classification of dengue, were strongly associated with death. No significant association was observed between any of the laboratory findings and death. Conclusions: The finding that epistaxis and persistent vomiting were also associated with death in children with severe dengue was unexpected and deserves to be explored in future studies. Because intensive care units are often limited in resource-poor settings, any information that can help to distinguish patients with severe dengue with a higher risk to progress to death may be crucial.

Psychiatric comorbidity, Restless Legs Syndrome and Nocturnal Eating Disorder: a case-control study

Objective: to evaluate the psychopathological profile in primary Restless Legs Syndrome (p-RLS) patients with and without nocturnal eating disorder (NED), analysing obsessive-compulsive traits, mood and anxiety disorder, and the two domains of personality proposed by Cloninger, temperament and character. Methods: we tested ten p-RLS patients without NED, ten p-RLS patients with NED and ten healthy control subjects, age and sex-matched, using Hamilton Depression and Anxiety Rating Scales, State-Trait Anxiety Inventory, Maudsley Obsessive Compulsive Inventory (MOCI) and Temperament and Character Inventory - revised (TCI). Results: p-RLS patients, particularly those with NED, had increased anxiety factor scores. MOCI-total, doubting and checking compulsion, and TCI-harm avoidance scores were significantly higher in p-RLS patients with NED. p-RLS patients without NED had significantly higher MOCI-doubting scores and a trend toward higher checking compulsion and harm avoidance scores with an apparent grading from controls to p-RLS patients without NED to p-RLS with NED. Conclusions: higher harm avoidance might predispose to display obsessive-compulsive symptoms, RLS and then, with increasing severity, compulsive nocturnal eating. RLS and NED could represent a pathological continuum in which a dysfunction in the limbic system, possibly driven by a dopaminergic dysfunction, could be the underlying pathophysiological mechanism.

Patient-related risk factors leading to aseptic stem loosening in total hip arthroplasty: a case-control study of 5,035 patients

BACKGROUND: We hypothesized that certain patient characteristics have different effects on the risk of early stem loosening in total hip arthroplasty (THA). We therefore conducted a case-control study using register-database records with the aim of identifying patient-specific risk factors associated with radiographic signs of aseptic loosening of the femoral component in THA. METHOD: Data were derived from a multinational European registry and were collected over a period of 25 years. 725 cases with radiographic signs of stem loosening were identified and matched to 4,310 controls without any signs of loosening. Matching criteria were type of implant, size of head, date of operation, center of primary intervention, and follow-up time. The risk factors analyzed were age at operation, sex, diagnosis and previous ipsilateral operations, height, weight, body mass index and mobility based on the Charnley classification. RESULTS: Women showed significantly lower risk of radiographic loosening than men (odds ratio (OR) 0.64). Age was also a strong factor: risk decreased by 1.8% for each additional year of age at the time of surgery. Height and weight were not associated with risk of loosening. A higher body mass index, however, increased the risk of stem loosening to a significant extent (OR 1.03) per additional unit of BMI. Charnley Class B, indicating restricted mobility, was associated with lower risk of loosening (OR 0.78). INTERPRETATION: An increased activity level, as seen in younger patients and those with unrestricted mobility, is an important factor in the etiology of stem loosening. If combined with high BMI, the risk of stem loosening within 10 years is even higher. A younger person should not be denied the benefits of a total hip arthroplasty but must accept that the risk of future failure is increased.

Influence of the menstrual cycle on the oral microbial flora in women: a case-control study including men as control subjects

Changes in the levels of female sex hormones during the menstrual cycle may cause cyclic differences in subgingival bacterial colonization patterns. The purpose of the present study was to test the hypothesis that hormonal changes in the menstrual cycle cause changes in the oral microbiota. METHODS: Bacterial plaque samples were collected in 20 systemically and periodontally healthy women using no hormonal contraceptives (test group) over a period of 6 weeks. Twenty age-matched systemically and periodontally healthy men were assigned to the control group. Samples were processed by checkerboard DNA-DNA hybridization assay, and 74 species were analyzed. RESULTS: No cyclic pattern of bacterial colonization was identified for any of the 74 species studied in women not using hormonal contraceptives. Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) (Y4) was common at the beginning of menstruation (mean: 32%) and increased during the following 2 weeks (36%) in women (P <0.05). No cyclic differences in bacterial presence were found among the men (P values varied between 0.14 and 0.98). Men presented with significantly higher bacterial counts for 40 of 74 species (P <0.001), including Staphylococcus aureus and Pseudomonas aeruginosa but not Porphyromonas gingivalis (P = 0.15) or Tannerella forsythia (previously T. forsythensis) (P = 0.42). CONCLUSIONS: During a menstruation period, cyclic variation in the subgingival microbiota of periodontally healthy women of child-bearing age who were not using oral hormonal contraceptives could not be confirmed. Male control subjects presented with higher levels of many species but also without a cyclic pattern.

Control design and genetic algorithm optimization for electrostatic MEMS

This dissertation discusses structural-electrostatic modeling techniques, genetic algorithm based optimization and control design for electrostatic micro devices. First, an alternative modeling technique, the interpolated force model, for electrostatic micro devices is discussed. The method provides improved computational efficiency relative to a benchmark model, as well as improved accuracy for irregular electrode configurations relative to a common approximate model, the parallel plate approximation model. For the configuration most similar to two parallel plates, expected to be the best case scenario for the approximate model, both the parallel plate approximation model and the interpolated force model maintained less than 2.2% error in static deflection compared to the benchmark model. For the configuration expected to be the worst case scenario for the parallel plate approximation model, the interpolated force model maintained less than 2.9% error in static deflection while the parallel plate approximation model is incapable of handling the configuration. Second, genetic algorithm based optimization is shown to improve the design of an electrostatic micro sensor. The design space is enlarged from published design spaces to include the configuration of both sensing and actuation electrodes, material distribution, actuation voltage and other geometric dimensions. For a small population, the design was improved by approximately a factor of 6 over 15 generations to a fitness value of 3.2 fF. For a larger population seeded with the best configurations of the previous optimization, the design was improved by another 7% in 5 generations to a fitness value of 3.0 fF. Third, a learning control algorithm is presented that reduces the closing time of a radiofrequency microelectromechanical systems switch by minimizing bounce while maintaining robustness to fabrication variability. Electrostatic actuation of the plate causes pull-in with high impact velocities, which are difficult to control due to parameter variations from part to part. A single degree-of-freedom model was utilized to design a learning control algorithm that shapes the actuation voltage based on the open/closed state of the switch. Experiments on 3 test switches show that after 5-10 iterations, the learning algorithm lands the switch with an impact velocity not exceeding 0.2 m/s, eliminating bounce.

A case-control study of sporadic Creutzfeldt-Jakob disease in Switzerland: analysis of potential risk factors with regard to an increased CJD incidence in the years 2001-2004

BACKGROUND: In 2001, the observed annual mortality from Creutzfeldt-Jakob disease (CJD) in Switzerland increased from less than 1.5 to 2.6 per million inhabitants. An underlying cause could not be identified. METHODS: To analyse potential risk factors for sCJD in Switzerland, close relatives of 69 sCJD-patients and 224 frequency age-matched controls were interviewed in a case-control study using a standardised questionnaire. 135 potential risk factors including socio-demographics, medical history, occupation and diet were analysed by logistic regression adjusting for age, sex and education. RESULTS: sCJD patients were more likely to have travelled abroad, worked at an animal laboratory, undergone invasive dental treatment, orthopaedic surgery, ophthalmologic surgery after 1980, regular GP visits, taken medication regularly, and consumed kidney. No differences between patients and controls were found for residency, family history, and exposure to environmental and other dietary factors. CONCLUSION: Although some factors were significantly more frequent among sCJD-cases, this study did not reveal specific explanations for the increased incidence of deaths due to sporadic CJD observed in Switzerland since 2001. Results have to be interpreted with caution due to multiple testing and possible recall bias in association with a long incubation period. The most plausible reason for the increase in Swiss sCJD cases after 2000 is an improved case ascertainment. Therefore, underreporting of cases might well have occurred before the year 2001, and the "real" yearly incidence of sCJD might not be lower than, but rather above 2 per million inhabitants.

Vascular risk factors and morphometric data in cervical artery dissection: a case-control study

BACKGROUND: Limited knowledge exists on vascular risk factors, body height and weight in patients with spontaneous cervical artery dissection (sCAD). PATIENTS AND METHODS: In this case-control study, major vascular risk factors, body weight, body height and body mass index (BMI) of 239 patients obtained from a prospective hospital-based sCAD registry were compared with 516 age- and sex-matched healthy controls undergoing systematic health examinations in the Clinical and Preventive Investigations Center, Paris. Gender-specific analyses were performed. RESULTS: The mean body height was higher in sCAD patients than in controls (171.3 cm (SD 8.6) vs 167.7 cm (8.9); p<0.0001) and sCAD patients had a significantly lower mean body weight (67.5 (12.2) kg vs 69.3 (14.6) kg; p<0.001) and mean BMI (22.9 (3.3) kg/m2 vs 24.5 (4.2) kg/m2; p<0.0001) than controls. The overall frequency of hypertension, diabetes, current smoking, past smoking and hypercholesterolaemia did not differ significantly between sCAD patients and controls. The mean total plasma cholesterol level was identical in both groups (5.5 mmol/l, SD 1.1). Gender specific subgroup analyses showed similar results for men and women. CONCLUSION: Patients with sCAD had a higher body height and a lower body weight and BMI than controls, while major vascular risk factors were similar in sCAD patients and controls.

Gingival labial recessions in orthodontically treated and untreated individuals: a case - control study

OBJECTIVES To evaluate the long-term development of labial gingival recessions during orthodontic treatment and retention phase. MATERIAL AND METHODS In this retrospective case-control study, the presence of gingival recession was scored (Yes or No) on plaster models of 100 orthodontic patients (cases) and 120 controls at the age of 12 (T12 ), 15 (T15 ), 18 (T18 ), and 21 (T21 ) years. In the treated group, T12 reflected the start of orthodontic treatment and T15 - the end of active treatment and the start of retention phase with bonded retainers. Independent t-tests, Fisher's exact tests and a fitted two-part "hurdle" model were used to identify the effect of orthodontic treatment/retention on recessions. RESULTS The proportion of subjects with recessions was consistently higher in cases than controls. Overall, the odds ratio for orthodontic patients as compared with controls to have recessions is 4.48 (p < 0.001; 95% CI: 2.61-7.70). CONCLUSIONS Within the limits of the present research design, orthodontic treatment and/or the retention phase may be risk factors for the development of labial gingival recessions. In orthodontically treated subjects, mandibular incisors seem to be the most vulnerable to the development of gingival recessions.