bluuebunny/crossref_metadata_2025 huggingface dataset:
Stochastic and reversible aggregation of mRNA with expanded CUG-triplet repeats
Authors: Querido Emmanuelle , Gallardo Franck , Beaudoin Mélissa , Ménard Catherine , Chartrand Pascal
Published: April 2011

Transcripts containing expanded CNG repeats, which are found in several neuromuscular diseases, are not exported from the nucleus and aggregate as ribonuclear inclusions by an unknown mechanism. Using the MS2–GFP system, which tethers fluorescent proteins to a specific mRNA, we followed the dynamics of single CUG-repeat transcripts and RNA aggregation in living cells. Single transcripts with 145 CUG repeats from the dystrophia myotonica-protein kinase (DMPK) gene had reduced diffusion kinetics compared with transcripts containing only five CUG repeats. Fluorescence recovery after photobleaching (FRAP) experiments showed that CUG-repeat RNAs display a stochastic aggregation behaviour, because individual RNA foci formed at different rates and displayed different recoveries. Spontaneous clustering of CUG-repeat RNAs was also observed, confirming the stochastic aggregation revealed by FRAP. The splicing factor Mbnl1 colocalized with individual CUG-repeat transcripts and its aggregation with RNA foci displayed the same stochastic behaviour as CUG-repeat mRNAs. Moreover, depletion of Mbnl1 by RNAi resulted in decreased aggregation of CUG-repeat transcripts after FRAP, supporting a direct role for Mbnl1 in CUG-rich RNA foci formation. Our data reveal that nuclear CUG-repeat RNA aggregates are labile, constantly forming and disaggregating structures, and that the Mbnl1 splicing factor is directly involved in the aggregation process.
TALE homeodomain proteins regulate site-specific terminal differentiation,LCEgenes and epidermal barrier
Authors: Jackson Ben , Brown Stuart J. , Avilion Ariel A. , O'Shaughnessy Ryan F. L. , Sully Katherine , Akinduro Olufolake , Murphy Mark , Cleary Michael L. , Byrne Carolyn
Published: April 2011

The epidermal barrier varies over the body surface to accommodate regional environmental stresses. Regional skin barrier variation is produced by site-dependent epidermal differentiation from common keratinocyte precursors and often manifests as site-specific skin disease or irritation. There is strong evidence for body-site-dependent dermal programming of epidermal differentiation in which the epidermis responds by altering expression of key barrier proteins, but the underlying mechanisms have not been defined. The LCE multigene cluster encodes barrier proteins that are differentially expressed over the body surface, and perturbation of LCE cluster expression is linked to the common regional skin disease psoriasis. LCE subclusters comprise genes expressed variably in either external barrier-forming epithelia (e.g. skin) or in internal epithelia with less stringent barriers (e.g. tongue). We demonstrate here that a complex of TALE homeobox transcription factors PBX1, PBX2 and Pknox (homologues of Drosophila Extradenticle and Homothorax) preferentially regulate external rather than internal LCE gene expression, competitively binding with SP1 and SP3. Perturbation of TALE protein expression in stratified squamous epithelia in mice produces external but not internal barrier abnormalities. We conclude that epidermal barrier genes, such as the LCE multigene cluster, are regulated by TALE homeodomain transcription factors to produce regional epidermal barriers.
A mitotic role for Mad1 beyond the spindle checkpoint
Authors: Emre Doruk , Terracol Régine , Poncet Anaïs , Rahmani Zohra , Karess Roger E.
Published: April 2011

Unattached kinetochores generate an anaphase inhibitor, through the spindle assembly checkpoint (SAC), that allows cells more time to establish proper kinetochore–microtubule (K–MT) linkages and thus avoid aneuploidy. Mad1 is the receptor for Mad2 at kinetochores, where it catalyzes the formation of Mad2–Cdc20 complexes, an essential part of the anaphase inhibitor, but whether it has any other mitotic function is unknown. We have generated a mad1-null mutation in Drosophila. This mutant is SAC defective and Mad2 is no longer localized to either nuclear envelope or kinetochores, but it displays normal basal mitotic timing. Unlike mad2 mutants, which have relatively normal mitoses, mad1 anaphases show high frequencies of lagging chromatids, at least some of which are caused by persistent merotelic linkages. A transgene expressing GFP–Mad1 rescues both the SAC and the anaphase defects. In an attempt to separate the SAC function from the mitotic function, we made a mad1 transgene with a mutated Mad2-binding domain. Surprisingly, this transgene failed to complement the anaphase phenotype. Thus, Mad1 has activity promoting proper K–MT attachments in addition to its checkpoint function. This activity does not require the presence of Mad2, but it does depend in some unknown way on key residues in the Mad2-binding domain of Mad1.
Isoform-specific phosphorylation of human linker histone H1.4 in mitosis by the kinase Aurora B
Authors: Hergeth Sonja P. , Dundr Miroslav , Tropberger Philipp , Zee Barry M. , Garcia Benjamin A. , Daujat Sylvain , Schneider Robert
Published: April 2011

The linker histone H1 plays an essential role in maintaining and establishing higher-order chromatin structure. As with core histones, histone H1 is also extensively covalently modified. We showed previously that phosphorylation of S27 in human histone H1.4 (H1.4S27-P), prevents binding of heterochromatin protein 1 (HP1) family members (officially known as chromobox protein homologs) to the neighboring dimethylated K26. Here, we present the first functional characterization of H1.4S27-P in vivo and in vitro. We show that H1.4S27 phosphorylation is cell-cycle-regulated and its levels peak on metaphase chromosomes. We identify further Aurora B as the kinase phosphorylating H1.4S27. We demonstrate that histone H1.4 is the only somatic linker histone variant targeted by Aurora B and that Aurora B exclusively phosphorylates S27. Adjacent K26 dimethylation can regulate Aurora B activity towards S27, uncovering a crosstalk between these modifications. Finally, our fluorescence recovery after photobleaching (FRAP) analysis on histone H1.4 mutants suggests a role of S27 phosphorylation in the regulation of histone H1.4 mobility and chromatin binding in mitosis.
Respiratory-gated 18F-FDG PET imaging in lung cancer: effects on sensitivity and specificity
Authors: Daouk Joël , Leloire Marie , Fin Loïc , Bailly Pascal , Morvan Julie , El Esper Isabelle , Saidi Lazhar , Moullart Véronique , François Géraldine , Jounieaux Vincent , Meyer Marc-Etienne
Published: April 2011

Background

Respiratory motion is known to deteriorate positron emission tomography (PET) images and may lead to potential diagnostic errors when a standardized uptake value (SUV) cut-off threshold is used to discriminate between benign and malignant lesions.

Purpose

To evaluate and compare ungated and respiratory-gated 18F-fluorodeoxyglucose PET/computed tomography (CT) methods for the characterization of pulmonary nodules.

Material and Methods

The list-mode acquisition during respiratory-gated PET was combined with a short breath-hold CT scan to form the CT-based images. We studied 48 lesions in 43 patients. PET images were analyzed in terms of the maximum SUV (SUVmax) and the lesion location.

Results

Using receiver-operating characteristic (ROC) curves, the optimal SUV cut-off thresholds for the ungated and CT-based methods were calculated to be 2.0 and 2.2, respectively. The corresponding sensitivity values were 83% and 92%, respectively, with a specificity of 67% for both methods. The two methods gave equivalent performance levels for the upper and middle lobes (sensitivity 93%, specificity 62%). They differed for the lower lobes, where the CT-based method outperformed the ungated method (sensitivity values of 90% and 70%, respectively, and a specificity of 73% with both methods) – especially for lesions smaller than 15 mm.

Conclusion

The CT-based method increased sensitivity and did not diminish specificity, compared with the ungated method. It was more efficient than the ungated method for imaging the lower lobes and smallest lesions, which are most affected by respiratory motion.
Outcome of HIV-infected patients transferred to a specialist inpatient unit
Authors: Whitehorn J , Edwards S G , Cartledge J D , Miller R F
Published: April 2011

The British HIV Association (BHIVA) recommends that specialist clinical networks are involved in care of HIV-positive patients admitted to district general hospitals (DGHs) and that transfer to a specialist HIV treatment centre is considered for each patient. We audited our experience of 29 patients transferred to our specialist inpatient unit over a two year period. Fifteen (52%) patients were known to be HIV-infected before admission to the referring hospital. Ten (71%) of 14 patients with newly diagnosed HIV had an opportunistic infection at transfer. At the referring hospital the time taken to diagnose HIV infection ranged from one to 26 days (median = 3.5). Only five patients (17%) were transferred by 72 hours of admission to the referring hospital. The duration of stay at our centre was 1–212 days (median = 15): seven patients (24%) required admission to the intensive care unit. Seven patients died; of these, three had newly diagnosed HIV infection. This audit demonstrates that sick HIV-infected patients transferred to a specialist HIV unit had a poor outcome and lengthy hospital admissions. Our audit supports roll-out of HIV testing to avoid adverse outcomes associated with late diagnosis and development of clinical networks involving specialist HIV treatment centres in order to support provision of HIV care in DGHs.
Long-term follow-up and survival of antiretroviral-naïve patients with cryptococcal meningitis in the pre-antiretroviral therapy era, Gauteng Province, South Africa
Authors: Park B J , Shetty S , Ahlquist A , Greenbaum A , Miller J L , Motsi A , McCarthy K , Govender N
Published: April 2011

Cryptococcal meningitis (CM) is a major cause of death among HIV-infected persons in sub-Saharan Africa. We conducted a study to describe the long-term outcomes during the pre-antiretroviral post-ART therapy period. Enrolled cases were those detected through population-based surveillance in Gauteng Province, South Africa, and diagnosed during March–November 2002 and July–September 2003 from eight large hospitals representing academic, provincial and rural settings. Of 1089 case-patients diagnosed with CM, 721 (70%) survived to discharge. Among the 256 with follow-up information, 154 (60%) were established to have died, 44% of whom died as outpatients. Overall, the 14- and 90-day survival post-diagnosis was 68% and 41%, respectively. On Cox proportional hazards multivariable analysis, severe disease was associated with shorter survival time; having received any antifungal treatment for the cryptococcal episode was associated with increased survival time at follow-up. Although most patients in this cohort survived the initial hospitalization, only 41% were still alive three months after diagnosis, with nearly half of deaths occurring outside a hospital. These data are an important baseline from which to measure effectiveness of public health management of CM in South Africa.
Clinical experience with nevirapine combined with tenofovir plus emtricitabine or lamivudine-containing regimens in HIV-infected subjects
Authors: Smith D E , Chan D J , Maruszak H , Jeganathan S
Published: April 2011

We retrospectively evaluated the durability and reasons for discontinuation of nevirapine (NVP) in combination with a tenofovir (TDF) and emtricitabine (FTC) or lamivudine (3TC)-containing antiretroviral therapy (ART) regimen in an Australian outpatient setting. Between January 2003 and June 2009, 64 patients (29 naïve and 35 treatment-experienced) received NVP/TDF-based regimens. The median exposure was 13.0 months (interquartile range [IQR] 6.0–20.0 months). The two- and three-year probability of continuing a NVP/TDF with FTC or 3TC regimen was 76% and 70%, respectively. Thirteen (20.3%) patients discontinued their regimen during the observation period. Reasons for discontinuation included virological failure in four (6.3%), rash in three (4.7%), lost to follow-up in three (4.7%), liver toxicity in two (3.1%) and HIV-1-related encephalopathy in one (1.6%). Long-term follow-up with a NVP/TDF-based regimen showed a low rate of discontinuation and enabled physicians to extend the use of ART over a long period, often with simplified (once-daily) regimens.
Acceptance of HIV testing in medical inpatients: a local acceptability study
Authors: Chan S Y , Hill-Tout R , Rodgers M , Cormack I
Published: April 2011

Late diagnosis remains the most important factor related to death due to HIV in the UK. To reduce late diagnosis, the British HIV Association (BHIVA), the British Association for Sexual Health and HIV (BASHH), and the British Infection Society jointly released national guidelines for HIV testing in the UK in 2008. They recommend local evaluation of HIV testing for all medical admissions aged 15–59 years in areas where the local prevalence is above 2/1000. The local prevalence of HIV in Croydon is 4.17/1000. We carried out a local acceptability study at Mayday Hospital in Croydon and found that 84/101 medical patients agreed to have an HIV test. A previous audit showed that only 9/1047 medical admissions had been tested for HIV. This study shows that HIV testing is acceptable and that more patients could be tested.
Universal prenatal HIV screening: are we there yet?
Authors: Kennedy M R , Meyn L A , Reeves M F , Wiesenfeld H C
Published: April 2011

The objectives of this study were to determine the prevalence of and factors associated with prenatal HIV screening and the availability of HIV test results in medical records in Pittsburgh, PA, USA. Three hundred postpartum women were surveyed about demographics and prenatal care provider(s) and practice setting and were asked to recall prenatal HIV screening and reasons for accepting or declining a HIV test. Medical records were reviewed for documentation of HIV results. Overall, 65% of women reported screening. White race, higher annual household income and fewer lifetime sexual partners were independently associated with decreased likelihood of prenatal HIV screening. Provider presentation of screening as standard practice and provider encouragement were associated with prenatal HIV screening. Only 38% of medical records contained HIV results at the time of labour. Universal and routine offering of prenatal HIV screening as standard practice, in conjunction with encouragement from health-care providers, may increase patient acceptability and the uptake of prenatal HIV screening.
Influence of hepatitis G virus (GB virus C) on the prognosis of HIV-infected women
Authors: Campos A F , Tengan F M , Silva S A A , Levi J E
Published: April 2011

This study was undertaken to evaluate the prevalence of GB virus C (GBV-C) viraemia and anti-E2 antibody, and to assess the effect of co-infection with GBV-C and HIV during a 10-year follow-up of a cohort of 248 HIV-infected women. Laboratory variables (mean and median CD4 counts, and HIV and GBV-C viral loads) and clinical parameters were investigated. At baseline, 115 women had past exposure to GBV-C: 57 (23%) were GBV-C RNA positive and 58 (23%) were anti-E2 positive. There was no statistical difference between the groups (GBV-C RNA + /anti-E2 − , GBV-C RNA − /anti-E2 + and GBV-C RNA − /anti-E2 − ) regarding baseline CD4 counts or HIV viral loads ( P = 0.360 and 0.713, respectively). Relative risk of death for the GBV-C RNA + /anti-E2 − group was 63% lower than that for the GBV-C RNA − /anti-E2 − group. Multivariate analysis demonstrated that only HIV loads ≥ 100,000 copies/mL and AIDS-defining illness during follow-up were associated with shorter survival after AIDS development. It is likely that antiretroviral therapy (ART) use in our cohort blurred a putative protective effect related to the presence of GBV-C RNA.
A case control study of anovaginal distance and bacterial vaginosis
Authors: Brotman R M , Melendez J H , Ghanem K G
Published: April 2011

We aimed to test the hypothesis that a short anovaginal distance may increase the risk of bacterial vaginosis (BV) due to faecal contamination and disruption of the vaginal microbiota. Women attending two sexually transmitted infection (STI) clinics in Baltimore, Maryland, USA, who complained of a vaginal discharge were asked to participate in a study to measure mucosal immune responses. In this pilot study of all enrolled women, a small plastic ruler was used to measure the anatomic distance from the posterior fourchette to the anus with the participant in the lithotomy position. Cases of BV, defined by Amsel's clinical criteria ( n = 62), were compared with controls ( n = 31) without BV. We used linear and logistic regression models to adjust for potential confounders. A total of 93 women were recruited (median age 28.6 years, 93% black, 4.4% gonorrhoea infection, 7.4% chlamydia infection, 8.6% trichomonas infection, 67% BV diagnosed). Mean anovaginal distance was 3.22 cm (SD: 0.74, range 1.8–5.2) for controls and 3.37 cm (SD: 0.76, range: 1.8–5.7) for cases ( P = 0.38). There was no difference between cases and controls when comparing median values, quartiles and after adjusting for potential confounders. Among high-risk women with multiple co-infections, there was no association between anovaginal distance and clinical diagnosis of BV.
Optimal Housing, Consumption, and Investment Decisions over the Life Cycle
Authors: Kraft Holger , Munk Claus
Published: April 2011

We derive explicit solutions to life-cycle utility maximization problems involving stock and bond investment, perishable consumption, and the rental and ownership of residential real estate. Prices of houses, stocks and bonds, and labor income are correlated. Because of a positive correlation between house prices and labor income, young individuals want little exposure to house price risk and tend to rent their home. Later in life the desired housing investment increases and will eventually reach and exceed the desired consumption, suggesting that the individual should buy his home—and either additional housing units (for renting out) or house price–linked financial assets. In the final years, preferences shift back to home rental. The derived strategies are still useful if housing positions are only reset infrequently. Our results suggest that markets for real estate investment trusts or other house price–linked contracts lead to nonnegligible welfare gains.

This paper was accepted by Wei Xiong, finance.
Performance Analysis of Queueing Networks via Robust Optimization
Authors: Bertsimas Dimitris , Gamarnik David , Rikun Alexander Anatoliy
Published: April 2011

Performance analysis of queueing networks is one of the most challenging areas of queueing theory. Barring very specialized models such as product-form type queueing networks, there exist very few results that provide provable nonasymptotic upper and lower bounds on key performance measures.

In this paper we propose a new performance analysis method, which is based on the robust optimization. The basic premise of our approach is as follows: rather than assuming that the stochastic primitives of a queueing model satisfy certain probability laws—such as i.i.d. interarrival and service times distributions—we assume that the underlying primitives are deterministic and satisfy the implications of such probability laws. These implications take the form of simple linear constraints, namely, those motivated by the law of the iterated logarithm (LIL). Using this approach we are able to obtain performance bounds on some key performance measures. Furthermore, these performance bounds imply similar bounds in the underlying stochastic queueing models.

We demonstrate our approach on two types of queueing networks: (a) tandem single-class queueing network and (b) multiclass single-server queueing network. In both cases, using the proposed robust optimization approach, we are able to obtain explicit upper bounds on some steady-state performance measures. For example, for the case of TSC system we obtain a bound of the form C(1 − ρ)−1 ln ln((1 − ρ)−1) on the expected steady-state sojourn time, where C is an explicit constant and ρ is the bottleneck traffic intensity. This qualitatively agrees with the correct heavy traffic scaling of this performance measure up to the ln ln((1 − ρ)−1) correction factor.
Dual-Monoclonal, Sandwich Immunoassay Specific for Glucose-Dependent Insulinotropic Peptide1-42, the Active Form of the Incretin Hormone
Authors: Troutt Jason S , Siegel Robert W , Chen Jinbiao , Sloan John H , Deeg Mark A , Cao Guoqing , Konrad Robert J
Published: April 2011

BACKGROUND

Glucose-dependent insulinotropic peptide (GIP) is an incretin peptide secreted by intestinal K cells that stimulates insulin secretion in a glucose-dependent manner. It is secreted as an active, intact 42–amino acid peptide GIP1-42, which is rapidly degraded by dipeptidyl peptidase 4 to GIP3-42, which is inactive. There is currently no described monoclonal antibody–based sandwich immunoassay to quantify concentrations of GIP1-42, the active form of the peptide.

METHODS

To create a sandwich ELISA for GIP1-42, we generated a monoclonal antibody specific for the intact N-terminus of the peptide, which was further optimized to increase its affinity. We used this antibody as a conjugate antibody in a sandwich ELISA and paired it with an anti–total GIP capture monoclonal antibody to create a dual monoclonal sandwich ELISA for GIP1-42.

RESULTS

The sandwich ELISA was highly specific for GIP1-42 and did not recognize GIP3-42. The ELISA demonstrated a broad dynamic range and a lower limit of quantification of 5 ng/L. Using the ELISA, we were able to show that GIP1-42 concentrations in healthy volunteers increased dramatically in the postprandial state compared to the fasting state. GIP1-42 values were correlated with total GIP values overall; however, there was substantial interindividual variation.

CONCLUSIONS

The use of an N-terminal–specific monoclonal antibody in a sandwich ELISA format provides a robust and convenient method for measuring concentrations of GIP1-42, the active form of the incretin hormone. This ELISA should help to improve our understanding of the role of GIP1-42 in regulating glucose-dependent insulin secretion.
Modeling Vertical Subcooled Boiling Flows at Low Pressures
Authors: Yeoh G. H. , Cheung S. C. P. , Tu J. Y. , Ho M. K. M
Published: April 2011

An improved wall heat flux partitioning model at the heated surface was developed by Yeoh et al. This model, coupled with a three-dimensional two-fluid model and Multiple Size Group model, has led to satisfactory agreement being achieved between the model predictions and experimental measurements. Nevertheless, one shortcoming is the reliance on empirical correlations for the active nucleation site density in the wall heat flux partitioning model. This discrepancy brings about uncertainties, especially in appropriately evaluating the vapor generation rate, which greatly influences the model prediction on the axial and radial void fraction profiles within the bulk fluid flow. By considering the fractal model with the aforementioned subcooled boiling flow model in the absence of empirical correlations for the active nucleation site density, a comprehensive mechanistic model to predict vertically oriented subcooled boiling flows is developed. The proposed model is assessed against the experimental data of axial measurements of Zeitoun and Shoukri and the radial measurements of Yun et al. and Lee et al. for vertical subcooled boiling flows within annular channels. Improved model predictions are obtained when the model is compared against typically applied empirical correlations for active nucleation site density. Discussions on the agreement of other two-phase flow parameters are also presented.
Development of a Garlic Clove Peeler for Small Scale Industry
Authors: Mudgal Vishvambhar Dayal , Champawat Padam Singh
Published: April 2011

Garlic (Allium sativum L.) has been used as a food, a condiment, and for medicinal purposes for over many centuries. The typical physical characteristics of garlic cloves make the peeling to be very tedious and time-consuming operation. Considering the increasing demand for garlic products in domestic and export market, a low cost garlic clove peeler was developed and its performance was evaluated. The developed garlic clove peeler consisted of a 130 mm diameter, 400 mm long peeling chamber mounted on a mild steel (MS) angle frame. The top portion of the pressure chamber was connected with a 40 mm diameter reducer to separate the thin husk from the peeled material. A 10 mm galvanized iron (GI) pipe was inserted and positioned at a height of 60 mm from the top surface of the garlic bed to flow the air from the compressor. The peeling efficiency of 97.6 percent was observed with peeling time of 70 s for a batch of 500 g.
Outcomes Associated with Influenza Vaccination in the First Year after Kidney Transplantation
Authors: Hurst Frank P. , Lee Jessica J. , Jindal Rahul M. , Agodoa Lawrence Y. , Abbott Kevin C.
Published: April 2011

Background and objectives

Influenza vaccination is recommended in all renal transplant recipients. However, immunosuppression in the early period post-transplant may attenuate the immunologic response to the vaccine. Additionally, it has been theorized that vaccination can induce an immune response that could trigger rejection episodes.

Design, setting, participants, & measurements

In a retrospective cohort of 51,730 adult Medicare primary patients who were first transplanted from January 2000 to July 2006 and followed through October 2006, we assessed Medicare claims for influenza vaccination and influenza infections, respectively. Outcomes included allograft loss and death.

Results

There were 9678 (18.7%) patients with claims for influenza vaccination in the first year post-transplant. Factors associated with vaccination included older age, diabetes, later year of transplant, and tacrolimus or mycophenolate at discharge. Vaccinations were less frequent among men, African Americans, highly sensitized patients, or those receiving induction immunosuppression or expanded criteria donor kidneys. Vaccination in the first year after transplant was associated with lower risk of subsequent allograft loss and death. Claims for influenza infection were reported in 310 (0.6%) patients and were not significantly associated with graft loss, although there was a trend toward death.

Conclusions

In the first year after renal transplantation, influenza vaccination was associated with a lower risk of subsequent allograft loss and death. Although this study cannot comment on formation of protective antibodies after vaccination, these data do not support withholding vaccination on the basis of concerns of adversely affecting allograft function.
Modeled Urea Distribution Volume and Mortality in the HEMO Study
Authors: Daugirdas John T. , Greene Tom , Depner Thomas A. , Levin Nathan W. , Chertow Glenn M.
Published: April 2011

Background and objectives

In the Hemodialysis (HEMO) Study, observed small decreases in achieved equilibrated Kt/Vurea were noncausally associated with markedly increased mortality. Here we examine the association of mortality with modeled volume (Vm), the denominator of equilibrated Kt/Vurea.

Design, setting, participants, & measurements

Parameters derived from modeled urea kinetics (including Vm) and blood pressure (BP) were obtained monthly in 1846 patients. Case mix–adjusted time-dependent Cox regressions were used to relate the relative mortality hazard at each time point to Vm and to the change in Vm over the preceding 6 months. Mixed effects models were used to relate Vm to changes in intradialytic systolic BP and to other factors at each follow-up visit.

Results

Mortality was associated with Vm and change in Vm over the preceding 6 months. The association between change in Vm and mortality was independent of vascular access complications. In contrast, mortality was inversely associated with V calculated from anthropometric measurements (Vant). In case mix–adjusted analysis using Vm as a time-dependent covariate, the association of mortality with Vm strengthened after statistical adjustment for Vant. After adjustment for Vant, higher Vm was associated with slightly smaller reductions in intradialytic systolic BP and with risk factors for mortality including recent hospitalization and reductions in serum albumin concentration and body weight.

Conclusions

An increase in Vm is a marker for illness and mortality risk in hemodialysis patients.
Chronic Kidney Disease in Octogenarians
Authors: Shastri Shani , Tighiouart Hocine , Katz Ronit , Rifkin Dena E. , Fried Linda F. , Shlipak Michael G. , Newman Anne B. , Sarnak Mark J.
Published: April 2011

Background and objectives

There are limited data on the prevalence of chronic kidney disease (CKD) and its clinical importance in the very old. We examined the prevalence of CKD in octogenarians and its association with cardiovascular disease (CVD).

Design, setting, participants, & measurements

In a cross-sectional analysis of 1028 participants from the Cardiovascular Health Study All Stars, we evaluated association of prevalent CKD with CVD using multivariable logistic regression. CKD was defined as eGFR of <60 ml/min per 1.73 m2. GFR was estimated using CKD-Epi creatinine and cystatin C equations that incorporate coefficients for age, gender, and race (eGFREPI, eGFRCYS3var) and the one-variable cystatin C equation (eGFRCYS1var). Prevalent CVD was defined as a composite of coronary heart disease, heart failure, and stroke.

Results

Mean age was 86 years, 64% were women, 86% were Caucasians, 14% had diabetes, and 39% had prevalent CVD. Mean eGFREPI, eGFRCYS3var, and eGFRCYS1var were 59, 62, and 70 ml/min per 1.73 m2, and 51%, 46%, and 33% had CKD, respectively. Associations of CKD with CVD varied by equation in adjusted analyses: CKDEPI (OR, 1.53; 95% CI, 1.15 to 2.03), CKDCYS3var (OR, 1.67; 95% CI, 1.25, 2.23), and CKDCYS1var (OR, 2.09; 95% CI, 1.55, 2.83).

Conclusions

Reduced eGFR is highly prevalent in octogenarians, and the eGFRCYS1var equation yielded the lowest prevalence of CKD but the strongest association with prevalent CVD. Because there are no validated estimating equations in the elderly, estimation of kidney function on the basis of on any one equation should be interpreted with caution.
Cancer-Specific Mortality in Chronic Kidney Disease
Authors: Weng Pei-Hsuan , Hung Kuan-Yu , Huang Hsien-Liang , Chen Jen-Hau , Sung Pei-Kun , Huang Kuo-Chin
Published: April 2011

Background and objectives

Chronic kidney disease (CKD) is known to be associated with increased all-cause and cardiovascular mortality, but no large studies examined the cancer-specific mortality in non–dialysis-dependent CKD patients. Such outcome data are needed for proper allocation of resources and would help to develop better preventive services.

Design, setting, participants, & measurements

Between 1998 and 1999, 123,717 adults were recruited from four health screening centers in Taiwan. The estimated glomerular filtration rate was calculated using the four-variable Modification of Diet in Renal Disease Study equation for the Chinese. Mortality was ascertained by computer linkage to the national death registry after a median follow-up of 7.06 years. Cox proportional hazards regression models were used to estimate the impact of CKD on cancer-specific mortality.

Results

A higher risk for overall cancer mortality was found in CKD patients compared with non-CKD patients (adjusted hazard ratio, 1.2). CKD was associated with increased mortality from liver cancer, kidney cancer, and urinary tract cancer, with an adjusted hazard ratio of 1.74, 3.3, and 7.3, respectively. A graded relationship between the severity of renal impairment and cancer mortality was also found.

Conclusions

Patients with CKD had a higher mortality risk of liver cancer, kidney cancer, and urinary tract cancer. This is the first large study that showed an inverse association between renal function and liver cancer mortality. The increased mortality could be caused by higher cancer incidence or worse response to cancer treatment. Future research is warranted to clarify the mechanism.
A Call to Action
Authors: Friedman Scott E. , Palac Robert T. , Zlotnick David M. , Chobanian Michael C. , Costa Salvatore P.
Published: April 2011

Background and objectives

Candidates for renal transplantation are at increased risk for complications related to cardiovascular disease; however, the optimal strategy to reduce this risk is not clear. The aim of this study was to evaluate the variability among existing guidelines for preoperative cardiac evaluation of renal transplant candidates.

Design, setting, participants, & measurements

A consecutive series of renal transplant candidates (n = 204) were identified, and four prominent preoperative cardiac evaluation guidelines, pertaining to this population, were retrospectively applied to determine the rate at which each guideline recommended cardiac stress testing.

Results

The rate of pretransplant cardiac stress testing would have ranged from 20 to 100% depending on which guideline was applied. The American Heart Association/American College of Cardiology (ACC/AHA) guideline resulted in the lowest rate of testing (20%). In our population, 178 study subjects underwent stress testing: 17 were found to have ischemia and 10 underwent revascularization. The ACC/AHA approach would have decreased the number of noninvasive tests from 178 to 39; it would have identified only 4 of the 10 patients who underwent revascularization. The three other guidelines (renal transplant–specific guidelines) recommended widespread pretransplant cardiac testing and thus identified nearly all patients who had ischemia on stress testing.

Conclusions

The ACC/AHA perioperative guideline may be inadequate for identifying renal transplant candidates with coronary disease; however, renal transplant–specific guidelines may provoke significant overtesting. An intermediate approach based on risk factors specific to the ESRD population may optimize detection of coronary disease and limit testing.
Elevated Non-high-density Lipoprotein Cholesterol (Non-HDL-C) Predicts Atherosclerotic Cardiovascular Events in Hemodialysis Patients
Authors: Shoji Tetsuo , Masakane Ikuto , Watanabe Yuzo , Iseki Kunitoshi , Tsubakihara Yoshiharu
Published: April 2011

Background and objectives

Dialysis patients show “reverse causality” between serum cholesterol and mortality. No previous studies clearly separated the risk of incident cardiovascular disease (CVD) and the risk of death or fatality after such events. We tested a hypothesis that dyslipidemia increases the risk of incident atherosclerotic CVD and that protein energy wasting (PEW) increases the risk of fatality after CVD events in hemodialysis patients.

Design, setting, participants, & measurements

This was an observational cohort study in 45,390 hemodialysis patients without previous history of myocardial infarction (MI), cerebral infarction (CI), or cerebral bleeding (CB) at the end of 2003, extracted from a nationwide dialysis registry in Japan. Outcome measures were new onsets of MI, CI, CB, and death in 1 year.

Results

The incidence rates of MI, CI, and CB were 1.43, 2.53, and 1.01 per 100 person-years, and death rates after these events were 0.23, 0.21, and 0.29 per 100 person-years, respectively. By multivariate logistic regression analysis, incident MI was positively associated with non-HDL cholesterol (non–HDL-C) and inversely with HDL cholesterol (HDL-C). Incident CI was positively associated with non–HDL-C, whereas CB was not significantly associated with these lipid parameters. Among the patients who had new MI, CI, and/or CB, death risk was not associated with HDL-C or non–HDL-C, but with higher age, lower body mass index, and higher C-reactive protein levels.

Conclusions

In this hemodialysis cohort, dyslipidemia was associated with increased risk of incident atherosclerotic CVD, and protein energy wasting/inflammation with increased risk of death after CVD events.
Differential Effect of Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Diabetes Management
Authors: Okada Sadanori , Morimoto Takeshi , Ogawa Hisao , Kanauchi Masao , Nakayama Masafumi , Uemura Shiro , Doi Naofumi , Jinnouchi Hideaki , Waki Masako , Soejima Hirofumi , Sakuma Mio , Saito Yoshihiko ,   for the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators
Published: April 2011

OBJECTIVE

Recent reports showed that low-dose aspirin was ineffective in the primary prevention of cardiovascular events in diabetic patients overall. We hypothesized that low-dose aspirin would be beneficial in patients receiving insulin therapy, as a high-risk group.

RESEARCH DESIGN AND METHODS

This study is a subanalysis of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial—a randomized, controlled, open-label trial. We randomly assigned 2,539 patients with type 2 diabetes and no previous cardiovascular disease to the low-dose aspirin group (81 or 100 mg daily) or to the no-aspirin group. The median follow-up period was 4.4 years. We investigated the effect of low-dose aspirin on preventing atherosclerotic events in groups receiving different diabetes management.

RESULTS

At baseline, 326 patients were treated with insulin, 1,750 with oral hypoglycemic agents (OHAs), and 463 with diet alone. The insulin group had the longest history of diabetes, the worst glycemic control, and the highest prevalence of diabetic microangiopathies. The diet-alone group had the opposite characteristics. The incidence of atherosclerotic events was 26.6, 14.6, and 10.4 cases per 1,000 person-years in the insulin, OHA, and diet-alone groups, respectively. In the insulin and OHA groups, low-dose aspirin did not affect atherosclerotic events (insulin: hazard ratio [HR] 1.19 [95% CI 0.60−2.40]; OHA: HR 0.84 [0.57−1.24]). In the diet-alone group, low-dose aspirin significantly reduced atherosclerotic events, despite the lowest event rates (HR 0.21 [0.05−0.64]).

CONCLUSIONS

Low-dose aspirin reduced atherosclerotic events predominantly in the diet-alone group and not in the insulin or OHA groups.
The Added Mass Coefficient computation of sphere, ellipsoid and marine propellers using Boundary Element Method
Authors: Ghassemi Hassan , Yari Ehsan
Published: April 2011

The Added Mass Coefficient computation of sphere, ellipsoid and marine propellers using Boundary Element Method

Added mass is an important and effective dynamic coefficient in accelerating, non uniform motion as a result of fluid accelerating around a body. It plays an important role, especially in vessel roll motion, control parameters as well as in analyzing the local and global vibration of a vessel and its parts like propellers and rudders. In this article, calculating the Added Mass Coefficient has been examined for a sphere, ellipsoid, marine propeller and hydrofoil; using numerical Boundary Element Method. Since an Ellipsoid and a sphere have simple geometric shapes and the Analytical values of their added mass coefficients are available, so that the results of added mass matrix are obtained and evaluated, using the boundary element method. Then the added mass matrix is computed in a given geometrical and flow specifications for a specific propeller and its results are studied versus experimental results, which it's current numerical data In comparison with other numerical methods has a good conformity with experimental results. The most important advantage of the method in determining the added mass matrix coefficients for the surface and underwater vessels and the marine propellers is extracting all the added mass coefficients with very good Accuracy, while in other numerical methods it is impossible to extract all the coefficients with the Desired Accuracy.
Reconstruction of the pelvis and lumbar-pelvic junction using 2 vascularized autologous bone grafts after en bloc resection for an iliosacral chondrosarcoma
Authors: Mendel Ehud , Mayerson Joel L. , Nathoo Narendra , Edgar Rick L. , Schmidt Carl , Miller Michael J.
Published: April 2011

Primary pelvic sarcomas remain challenging and complex surgical problems with significant potential for postoperative impairment of ambulation, as well as bowel, bladder, and sexual function. En bloc resection with negative tumor margins represents the best chance of control or cure as current adjuvant therapies remain ineffective. Tumor involvement of the sacrum with extension to the greater sciatic notch and ipsilateral ilium requires an external hemipelvectomy and sagittal sacrectomy with sacrifice of the lower extremity to achieve en bloc resection, followed by lumbar-pelvic reconstruction. A patient with an iliosacral chondrosarcoma is presented to illustrate a novel lumbar-pelvic reconstruction technique, in which vascularized soft tissue and 2 vascularized bone grafts were harvested from the amputated lower extremity and transferred to the pelvis as composite flaps to restore pelvic ring integrity, augment lumbar-pelvic fusion, and close the soft-tissue defect. The biomechanical dynamics of this unique construct are discussed.
Amyand Hernia with Appendicitis
Authors: Yagnik Vipul D.
Published: April 2011

The term Amyand hernia refers to presence of appendix within inguinal hernia. The incidence of having a normal appendix within inguinal hernia is about 1%, whereas the finding of appendicitis in the inguinal hernia is only 0.1%.
Association of Aortic and Main Left Coronary Aneurysms with Severe Aortic Insufficiency in Takayasu’s Arteritis
Authors: Schafranski Marcelo Derbli , Ferraz de Freitas Marcelo , Valladão de Carvalho Marcelo
Published: April 2011

Takayasu’s arteritis is a granulomatous vasculitis of unknown etiology that affects mainly the aorta and its branches. As a result of intimal fibroproliferation, segmental stenosis, occlusion, dilatation, and aneurysmal formation of the involved vessels may develop. It is an uncommon disease and usually affects young Asian female patients during the second and third decades of life. Coronary arteries are exceptionally affected and coronary aneurysm formation is a very rare finding. We describe a case of a previously healthy 26-year-old Caucasian female whose Takayasu’s arteritis presented as a previously undescribed association of aortic and main left coronary aneurysms with severe aortic insufficiency.
Angled Eccentric Osteosynthesis, a New Technique for Simple Mandibular Fractures
Authors: Lee Jeong Keun
Published: April 2011

Working and balancing sides are subject to torsional and the tensile stresses, respectively. Tension banding principle denotes the principle of plating along the tension line for stable internal fixation on the balancing side of the mandibular fracture, which is the theoretical basis for the miniplate osteosynthesis. On the contrary, Arbeitsgemeinschaft fϋr Osteo - synthesefragen/Association for the Study of Internal Fixation (AO/ASIF) introduced the idea of stable fixation which confirms the stability of the fracture segment across the fracture line of the working side. Merging the principles of the miniplate osteosynthesis and compression osteosynthesis, the author suggests a new technique of angled eccentric osteosynthesis in case of simple mandibular fractures. The drilling holes are eccentrically positioned away from the fracture gap and intentionally angled to each other. The advancement of the miniscrews through these eccentrically angled drill holes will exert an axial load toward the fracture gap providing an interfragmental compressive force.
Marine sediment pore‐water profiles of phosphate d18O using a refined micro‐extraction
Authors: Goldhammer Tobias , Max Thomas , Brunner Benjamin , Einsiedl Florian , Zabel Matthias
Published: April 2011

Phosphorus cycling in the ocean is influenced by biological and geochemical processes that are reflected in the oxygen isotope signature of dissolved inorganic phosphate (Pi). Extending the Pi oxygen isotope record from the water column into the seabed is difficult due to low Pi concentrations and small amounts of marine porewaters available for analysis. We obtained porewater profiles of Pi oxygen isotopes using a refined protocol based on the original micro‐extraction designed by Colman (2002). This refined and customized method allows the conversion of ultra‐low quantities (0.5 – 1 µmol) of porewater Pi to silver phosphate (Ag3PO4) for routine analysis by mass spectrometry. A combination of magnesium hydroxide co‐precipitation with ion exchange resin treatment steps is used to remove dissolved organic matter, anions, and cations from the sample before precipitating Ag3PO4. Samples as low as 200 µg were analyzed in a continuous flow isotope ratio mass spectrometer setup. Tests with external and laboratory internal standards validated the preservation of the original phosphate oxygen isotope signature (δ18OP) during micro extraction. Porewater data on δ18OP has been obtained from two sediment cores of the Moroccan margin. The δ18OP values are in a range of +19.49 to +27.30‰. We apply a simple isotope mass balance model to disentangle processes contributing to benthic P cycling and find evidence for Pi regeneration outbalancing microbial demand in the upper sediment layers. This highlights the great potential of using δ18OP to study microbial processes in the subseafloor and at the sediment water interface.
Extraction of monomethylmercury from seawater for low‐femtomolar determination
Authors: Bowman Katlin L. , Hammerschmidt Chad R.
Published: April 2011

Humans are exposed to toxic monomethylmercury (MMHg) principally by the consumption of marine fish. However, and due in part to analytical limitations, little is known about the distribution, sources, and biogeochemical cycling of MMHg in the ocean, where aqueous concentrations are in the femtomolar range and often less than current limits of detection. Here, we present a simple method for extraction and analysis of MMHg in seawater that has a detection limit of about 2 fM for a 2‐L sample, which is a 10‐fold improvement over current approaches. The technique, which is readily adaptable to a shipboard laboratory, involves purging and quantification of dimethylmercury (DMHg) from an unaltered 2‐L water sample followed by acidification to 1% with H2SO4 for > 6 h, pH neutralization, derivatization of MMHg in the seawater matrix with an ethylating agent, and purge‐and‐trap analysis with gas‐chromatographic cold‐vapor atomic fluorescence spectrometry. The method was developed and validated with analyses of seawater from the North Atlantic and Pacific Oceans, in addition to two fresh waters. This technique can be used to quantify, differentiate, and develop an improved understanding of the biogeochemistries of MMHg and DMHg in the ocean.