bluuebunny/crossref_metadata_2025 huggingface dataset:
Empagliflozin, a novel selective sodium glucose cotransporter‐2 (SGLT‐2) inhibitor: characterisation and comparison with other SGLT‐2 inhibitors
Authors: Grempler R. , Thomas L. , Eckhardt M. , Himmelsbach F. , Sauer A. , Sharp D. E. , Bakker R. A. , Mark M. , Klein T. , Eickelmann P.
Published: October 2011

Aims: Empagliflozin is a selective sodium glucose cotransporter‐2 (SGLT‐2) inhibitor in clinical development for the treatment of type 2 diabetes mellitus. This study assessed pharmacological properties of empagliflozin in vitro and pharmacokinetic properties in vivo and compared its potency and selectivity with other SGLT‐2 inhibitors.

Methods: [14C]‐alpha‐methyl glucopyranoside (AMG) uptake experiments were performed with stable cell lines over‐expressing human (h) SGLT‐1, 2 and 4. Two new cell lines over‐expressing hSGLT‐5 and hSGLT‐6 were established and [14C]‐mannose and [14C]‐myo‐inositol uptake assays developed. Binding kinetics were analysed using a radioligand binding assay with [3H]‐labelled empagliflozin and HEK293‐hSGLT‐2 cell membranes. Acute in vivo assessment of pharmacokinetics was performed with normoglycaemic beagle dogs and Zucker diabetic fatty (ZDF) rats.

Results: Empagliflozin has an IC50 of 3.1 nM for hSGLT‐2. Its binding to SGLT‐2 is competitive with glucose (half‐life approximately 1 h). Compared with other SGLT‐2 inhibitors, empagliflozin has a high degree of selectivity over SGLT‐1, 4, 5 and 6. Species differences in SGLT‐1 selectivity were identified. Empagliflozin pharmacokinetics in ZDF rats were characterised by moderate total plasma clearance (CL) and bioavailability (BA), while in beagle dogs CL was low and BA was high.

Conclusions: Empagliflozin is a potent and competitive SGLT‐2 inhibitor with an excellent selectivity profile and the highest selectivity window of the tested SGLT‐2 inhibitors over hSGLT‐1. Empagliflozin represents an innovative therapeutic approach to treat diabetes.
The relationship between obesity and hypoferraemia in adults: a systematic review
Authors: Cheng H. L. , Bryant C. , Cook R. , O'Connor H. , Rooney K. , Steinbeck K.
Published: October 2011

A growing number of studies suggest a potential link between obesity and altered iron metabolism. The purpose of this systematic review was to examine existing literature on iron status in obese populations. A comprehensive literature search was conducted. Included studies recruited participants ≥ 18 years with a body mass index ≥ 30 kg m−2 and provided descriptive statistics for haemoglobin or ferritin at a minimum. There were 25 studies meeting all eligibility criteria, of these 10 examined iron status in free‐living obese individuals and 15 reported baseline iron biomarkers from bariatric surgery candidates. Non‐obese comparison groups were used by 10 (40%) articles. In these, seven obese groups reported higher mean haemoglobin concentration; six reported significantly higher ferritin concentration; and four significantly lower transferrin saturation. Due to insufficient data, it was not possible to make conclusions regarding mean differences for soluble transferrin receptor (sTfR), hepcidin or C‐reactive protein. Existing evidence suggests a tendency for higher haemoglobin and ferritin concentration and lower transferrin saturation in obesity. Alternation of iron biomarkers in obese populations may be a result of obesity‐related inflammation and/or related comorbidities. Further research incorporating measurement of inflammatory cytokines, sTfR and hepcidin is required to confirm the impact of obesity on iron status.
Simultaneous estimation of hazard rates of several exponential populations
Authors: Mahapatra A. K. , Kumar Somesh , Vellaisamy P.
Published: October 2011

Suppose independent random samples are drawn from k (2) populations with a common location parameter and unequal scale parameters. We consider the problem of estimating simultaneously the hazard rates of these populations. The analogues of the maximum likelihood (ML), uniformly minimum variance unbiased (UMVU) and the best scale equivariant (BSE) estimators for the one population case are improved using Rao‐Blackwellization. The improved version of the BSE estimator is shown to be the best among these estimators. Finally, a class of estimators that dominates this improved estimator is obtained using the differential inequality approach.
Flexible Semiparametric Analysis of Longitudinal Genetic Studies by Reduced Rank Smoothing
Authors: Wang Yuanjia , Huang Chiahui , Fang Yixin , Yang Qiong , Li Runze
Published: October 2011

In longitudinal genetic studies, investigators collect repeated measurements on a trait that changes with time along with genetic markers. For family-based longitudinal studies, since repeated measurements are nested within subjects and subjects are nested within families, both the subject level and the measurement level correlations must be taken into account in the statistical analysis to achieve more accurate estimation. In such studies, the primary interests include testing for a quantitative trait locus effect, and estimating the age-specific quantitative trait locus effect and residual polygenic heritability function. We propose flexible semiparametric models and their statistical estimation and hypothesis testing procedures for longitudinal genetic data. We employ penalized splines to estimate non-parametric functions in the model. We find that misspecifying the baseline function or the genetic effect function in a parametric analysis may lead to a substantially inflated or highly conservative type I error rate on testing and large mean-squared error on estimation. We apply the proposed approaches to examine age-specific effects of genetic variants reported in a recent genomewide association study of blood pressure collected in the Framingham Heart Study.
Divine Hiddenness: Would More Miracles Solve the Problem?
Authors: O'Connell Jake H.
Published: October 2011

This article addresses the question of whether God's existence would be obvious to everyone if God performed more miracles. I conclude that it would not be so. I look at cases where people have been confronted with what they believe to be miracles and have either not come to believe in God, or have come to intellectual belief in God but declined to follow him. God's existence could be made undeniable not by spectacular signs, but only by God impressing his existence upon us in a direct, non‐propositional way.
Evaluation of the efficacy and safety of a CS20® protective barrier gel containing OGT compared with topical aciclovir and placebo on functional and objective symptoms of labial herpes recurrences: a randomized clinical trial
Authors: Khemis A. , Duteil L. , Coudert A.C. , Tillet Y. , Dereure O. , Ortonne J.P.
Published: October 2011

Background  Topical or systemic antiviral drugs reduce the duration of herpes simplex virus 1 (HSV‐1) recurrences but may not alleviate functional symptoms.

Objectives  To assess the efficacy and safety of CS20 (Acura 24®) protective barrier gel versus topical aciclovir and placebo in resolving functional symptoms in HSV‐1 labial recurrences.

Methods  A prospective, randomized, single‐centre, assessor‐blinded study of CS20 versus topical aciclovir or placebo. The primary endpoint was the total score of four herpes‐related functional symptoms (pain, burning, itching, and tingling sensations), evaluated by visual analogue scale (VAS). Secondary endpoints encompassed objective skin changes (oedema, crusting and erythema), evaluated by specific clinical scores.

Results  In a study of 106 patients, compared with placebo, a significant improvement in total functional symptom score was observed after 1 day of treatment in the CS20 group, but only after 7 days of treatment in the topical aciclovir group. Burning sensations were significantly reduced by CS20 compared with aciclovir (Days 1–2) or placebo (Days 1–7). Compared to placebo, CS20 significantly reduced pain intensity on Days 1–6. CS20 induced significant and early improvements in the clinical scores for oedema and crusting compared with placebo. Time to cure was similar for CS20 and aciclovir. The treatments were well tolerated and adverse events were comparable in the three treatment groups.

Limitations  The single‐centre and single‐blind design of the study and the preselection of patients.

Conclusion  CS20 showed superior effectiveness against functional symptoms (pain and burning) associated with HSV‐1 labial recurrences and was similar to aciclovir for time to cure.
Insulin‐like growth factor‐I gene polymorphism in acne vulgaris
Authors: Tasli L. , Turgut S. , Kacar N. , Ayada C. , Coban M. , Akcilar R. , Ergin S.
Published: October 2011

Background  Acne vulgaris is a multifactorial disease of the skin. Several studies have shown that elevated levels of serum insulin‐like growth factor‐I (IGF‐I) correlate with overproduction of sebum and acne. Recently functional relationship between IGF‐I (CA) polymorphism and circulating IGF‐I levels in adults has been reported.

Aims  The aim of our study was to investigate for the first time whether IGF‐I (CA) polymorphism might be involved in the pathogenesis of acne or not.

Methods  We included 115 acne patients and 117 healthy subjects to the study. The clinical grade of acne was assessed based on the Global Acne Grading System. Participants were questioned about diabetes mellitus, PCOS and other systemic disease. We searched for the IGF‐I (CA) 19 polymorphism in this study. The IGF‐I (CA) 19 polymorphism was performed by polymerase chain reaction.

Results  We categorized the IGF‐I (CA) 19 polymorphism area into three groups as lower than 192 bp, 192–194 bp and higher than 194 bp. We found that the frequency of genotype IGF‐1 (CA) 19 gene was significantly different between control and acne patients (P = 0.0002). A significant association between IGF‐I (CA) genotypes and severity of acne was found (P = 0.015). No significant difference was found between male and female patients (P > 0.05).

Conclusions  Our results suggest that IGF‐I (CA) 19 polymorphism may contribute to a predisposition to acne in Turkish patients.
Is it better in the moonlight? Nocturnal activity of insular cottonmouth snakes increases with lunar light levels
Authors: Lillywhite H. B. , Brischoux F.
Published: October 2011

Both theoretical and empirical investigations suggest that predation risk and availability of resources interact as trade‐offs to produce patterns of predation‐sensitive foraging. Such interactions have been explored intensely in terrestrial predator–prey systems where both nocturnal prey and predators adjust their activity and foraging behaviour to levels of moonlight. In the case of prey, higher levels of moonlight increase predation risks, and thus prey display lower levels of activity and/or shifts in their use of microhabitat during full moon nights. Predators also display parallel modifications of their activity rhythms during full moon nights – but why? Are predators also sensitive to increased predation, or do predators adjust their behaviour to that of their prey in order to optimize foraging success? Herein, we examined nocturnal predatory behaviour in a natural system where insular cottonmouth snakes, Agkistrodon piscivorus conanti, forage for fish carrion that is indifferent to levels of moonlight, thereby removing complexities linked to the behavioural patterns of prey. Our results demonstrated that insular cottonmouths increase their activity during full moon nights. Predation pressure on snakes foraging in the open does not seem to drive their nocturnal behaviour insofar as small‐sized individuals – presumably more susceptible to predation – are equally abundant as adult snakes irrespective of levels of moonlight. These results suggest that variation in predator's activity in natural predator–prey systems during risky (full moon) nights might be attributable principally to the availability and detectability of prey rather than a foraging‐safety trade‐off specific to the predator.
The NHS cervical screening programme audit of invasive cervical cancers: who benefits?
Authors: Moss EL , Sherman SM , Pearmain P , Redman CWE
Published: October 2011

Please cite this paper as: Moss E, Sherman S, Pearmain P, Redman C. The NHS cervical screening programme audit of invasive cervical cancers: who benefits? BJOG 2012;119:1–4.
Risk of recurrence and subsequent delivery after obstetric anal sphincter injuries
Authors: Baghestan E , Irgens LM , Børdahl PE , Rasmussen S
Published: October 2011

Please cite this paper as: Baghestan E, Irgens L, Børdahl P, Rasmussen S. Risk of recurrence and subsequent delivery after obstetric anal sphincter injuries. BJOG 2012;119:62–69.

Objective  To investigate the recurrence risk, the likelihood of having further deliveries and mode of delivery after third to fourth degree obstetric anal sphincter injuries (OASIS).

Design  Population‐based cohort study.

Setting  The Medical Birth Registry of Norway.

Population  A cohort of 828 864 mothers with singleton, vertex‐presenting infants, weighing 500 g or more, during the period 1967–2004.

Methods  Comparison of women with and without a history of OASIS with respect to the occurrence of OASIS, subsequent delivery rate and planned caesarean rate.

Main outcome measures  OASIS in second and third deliveries, subsequent delivery rate and mode of delivery.

Results  Adjusted odds ratios of the recurrence of OASIS in women with a history of OASIS in the first, and in both the first and second deliveries, were 4.2 (95% CI 3.9–4.5; 5.6%) and 10.6 (95% CI 6.2–18.1; 9.5%), respectively, relative to women without a history of OASIS. Instrumental deliveries, in particular forceps deliveries, birthweights of 3500 g or more and large maternity units were associated with a recurrence of OASIS. Instrumental delivery did not further increase the excess recurrence risk associated with high birthweight. A man who fathered a child whose delivery was complicated by OASIS was more likely to father another child whose delivery was complicated by OASIS in another woman who gave birth in the same maternity unit (adjusted OR 2.1; 95% CI 1.2–3.7; 5.6%). However, if the deliveries took place in different maternity units, the recurrence risk was not significantly increased (OR 1.3; 95% CI 0.8–2.1; 4.4%). The subsequent delivery rate was not different in women with and without previous OASIS, whereas women with a previous OASIS were more often scheduled to caesarean delivery.

Conclusion  Recurrence risks in second and third deliveries were high. A history of OASIS had little or no impact on the rates of subsequent deliveries. Women with previous OASIS were delivered more frequently by planned caesarean delivery.
Impact of mode of delivery on levator morphology: a prospective observational study with three‐dimensional ultrasound early in the postpartum period
Authors: Albrich SB , Laterza RM , Skala C , Salvatore S , Koelbl H , Naumann G
Published: October 2011

Please cite this paper as: Albrich S, Laterza R, Skala C, Salvatore S, Koelbl H, Naumann G. Impact of mode of delivery on levator morphology: a prospective observational study with three‐dimensional ultrasound early in the postpartum period. BJOG 2012;119:51–61.

Objective  To evaluate morphology and integrity of the levator ani muscle (LAM) with three‐dimensional ultrasound early in the postpartum period.

Design  Prospective cross‐sectional observational study.

Setting  University hospital in Germany.

Population  Women after vaginal delivery and caesarean section with no previous vaginal delivery.

Methods  Three‐dimensional perineal ultrasound was performed between 48 and 72 hours postpartum. The axial plane at the level of minimal hiatal dimension and tomographic ultrasound imaging were used to determine LAM biometry and defect.

Main outcome measures  Primary outcome was to compare hiatal dimensions and levator defect following vaginal delivery or caesarean section. For secondary outcomes, we evaluated the role of caesarean section in protecting levator integrity, and the possible involvement of the first stage of labour in LAM changes.

Results  In all, 157 women participated: 81 (51.6%) following vaginal delivery (70 spontaneous and 11 operative deliveries) and 76 (48.4%) following caesarean section (55 elective and 21 emergency caesarean sections). All biometric indices of the levator were higher after vaginal delivery (P < 0.001), except for LAM thickness. LAM defects were found to be significantly associated with vaginal delivery, with relative risk 7.5 (P < 0.001). Following vaginal delivery, 32 (39.5%) levator defects were found: 27 (38.5%) after spontaneous delivery and five (45.4%) after operative delivery. Four (5.2%) women had a levator defect following emergency caesarean section.

Conclusion  Vaginal delivery modifies and damages the LAM: the risk of levator defect after vaginal delivery is more than seven times higher than after caesarean section. Despite this, emergency caesarean section seems to have no complete preventive effect on LAM trauma.
Phosphorylation of microtubule‐associated protein tau by AMPK‐related kinases
Authors: Yoshida Hirotaka , Goedert Michel
Published: October 2011

J. Neurochem. (2012) 120, 165–176.

Microtubule‐associated protein tau is abnormally hyperphosphorylated in the intracellular filamentous inclusions seen in neurodegenerative disorders with dementia, such as Alzheimer’s disease and other tauopathies. Microtubule‐associated protein/microtubule‐affinity regulating kinases (MARKs) have previously been identified as kinases which phosphorylate KxGS motifs in the tandem repeats of tau. They are members of the 5′‐AMP‐activated protein kinase (AMPK)‐related kinases in the Ca2+/calmodulin‐dependent protein kinase group. In this study, we examined the ability of AMPK‐related kinases, brain‐specific kinases 1 and 2, maternal embryonic leucine‐zipper kinase, MARK1, and salt‐inducible kinase (SIK), to phosphorylate tau. We found that they phosphorylated S262 and S356 in KxGS motifs in the repeats of tau, thus resulting in immunoreactivity with antibody 12E8. MARK1 and SIK most effectively phosphorylated tau, and their down‐regulation resulted in a reduction of 12E8‐labelling. BX 795, an inhibitor of MARK1 and SIK, reduced 12E8‐immunolabelling of tau in rat cortical neurons. These findings reveal a significant contribution of AMPK‐related kinases to the phosphorylation of tau at S262/S356.
Blood flow–restricted walking does not result in an accumulation of metabolites
Authors: Loenneke Jeremy P. , Thrower Austin D. , Balapur Abhishek , Barnes Jeremy T. , Pujol Thomas J.
Published: October 2011

The American College of Sports Medicine recommends lifting a weight of at least 70% of one’s concentric one repetition maximum to achieve muscular hypertrophy as it is believed that anything below this intensity does not produce significant muscle growth. Recent studies have found muscle hypertrophy to occur with low‐intensity ‘aerobic–like’ exercise with the application of blood flow restriction (BFR) to the limbs. Previous research with low load resistance training has shown that elastic knee wraps provide a practical means to induce elevations in whole blood lactate (WBL), which has been hypothesized to result in many of the adaptations observed with this type of exercise. However, this has yet to be investigated with low‐intensity walking. Thus, the purpose of this paper was to determine the degree to which WBL increases with practical BFR walking. Exercise consisted of five 2‐min bouts of walking at 75 m per min on a motor‐driven treadmill with a 1‐min rest period following each exercise bout. Participants completed the walking with (BFR) and without [control (CON)] restriction to the upper thigh in a randomized order. Practical BFR with elastic knee wraps did statistically increase WBL compared with CON; however, this was not considered a real change because the minimal difference between conditions was not exceeded. In conclusion, metabolic stress is not increased following practical BFR walking exercise. This study may provide an explanation for the lower hormone response observed with BFR walking and provide further evidence that mechanisms other than metabolic accumulation exist with BFR.
The use of transcutaneous oximetry to predict complications of chronic wound healing: A systematic review and meta‐analysis
Authors: Arsenault Kyle A. , McDonald Joey , Devereaux P. J. , Thorlund Kristian , Tittley Jacques G. , Whitlock Richard P.
Published: October 2011

Transcutaneous oximetry (PtcO2) has been proposed as a method to predict nonhealing of chronic wounds and the occurrence of healing complications. However, the validity of this method as an independent predictor and an optimal threshold value for this tool are poorly defined. We undertook a systematic review and meta‐analysis to address these questions, searching five major medical databases, relevant review articles, and reference lists. We included all studies that used multivariable analysis to evaluate PtcO2 for its ability to predict chronic wound healing complications. Article selection and data abstraction were conducted independently and in duplicate. Four studies, enrolling 901 patients with 910 lower extremity chronic wounds, met our inclusion criteria. These studies showed that a peri‐wound PtcO2 level below a cutoff of 20 mmHg or 30 mmHg was an independent predictor of chronic wound healing complications (odds ratio 3.21, 95% confidence interval 1.07–9.69, I2 = 77%). A threshold value of 20 mmHg was used most frequently in the included studies and showed the strongest association. This review was limited by the small number of studies, a possible reporting bias, and heterogeneity. These results suggest that PtcO2 measurements have independent prognostic value in the assessment of chronic wounds, but further research is required to confirm these findings and define an optimal threshold value.
Constraining cooling histories: rutile and titanite chronology and diffusion modelling in NW Bhutan
Authors: WARREN C. J. , GRUJIC D. , COTTLE J. M. , ROGERS N. W.
Published: October 2011

U–Pb analyses of rutile and titanite commonly yield ages that constrain the timing of cooling rather than the timing of their crystallization. Rutile which grew at or close to peak temperature conditions in a mafic granulite, intermediate granulite and mafic amphibolite within juxtaposed litho/tectonostratigraphic units in the Greater Himalayan Sequence (GHS) of NW Bhutan yield LA–MC–ICP–MS U–Pb lower intercept cooling ages of 10.1 ± 0.4, 10.8 ± 0.1 and 10.0 ± 0.3 Ma, respectively. Numerical finite‐difference diffusion models constrained by previously published temperature–time and Pb diffusion data suggest that these ages are best explained by rapid cooling from peak temperature conditions of ∼800 °C at 14 Ma in the granulite‐bearing unit and ∼650 °C at 12 Ma in the amphibolite‐bearing unit. The good fit between the model and analysed ages confirms the relatively high retention of Pb in rutile suggested by the experimental data. Titanite that grew during an exhumation‐related amphibolite facies overprint on an eclogite facies mineral assemblage from the neighbouring Jomolhari Massif yields a U–Pb lower intercept cooling age of 14.6 ± 1.2 Ma. Diffusion modelling suggests that this age is too old to be consistent with the temperature–time paths inferred for the rutile‐bearing samples. Instead, the titanite age suggests cooling from ∼650 °C at an earlier time of 17–15 Ma, implying that the high‐grade rocks in the Jomolhari Massif experienced a different cooling history from the rest of the GHS in NW Bhutan. Together these data show that high‐grade rocks from three apparently different structural levels of the GHS in NW Bhutan experienced rapid cooling at >40 °C Ma−1 at varying times. The highest grade granulite facies rocks were exhumed from deeper structural levels that are not exposed, not preserved, or not yet recognized west of eastern Nepal. A progressive along‐strike change in tectonic regime, metamorphic history and/or exhumation mechanism across the orogen is implied by these thermochronologic data.
Effects of Phenology at Burn Time on Post‐Fire Recovery in an Invasive C4 Grass
Authors: Ruckman Erin M. , Schwinning Susanne , Lyons Kelly G.
Published: October 2011

The spread of non‐indigenous, C4 grasses threatens global conservation of savannas and subtropical grasslands. Identifying control methods to selectively target these invasives has proven difficult. Here, we tested the hypothesis that the effectiveness of prescribed burns for control is determined, in part, by the phenology of the target species at burn time. We conducted two experiments in a subhumid, C4 grassland in central Texas. The focal invasive was the C4, perennial bunchgrass Bothriochloa ischaemum (L.) Keng (KR bluestem). Burns were conducted in early and late fall when plants were in different phenological states. In addition, we attempted to manipulate phenological state through temporary rainout shelters to expedite maturation. The two experiments differed in the timing of the rainout shelter application (experiment 1: May to July, experiment 2: August and September), but otherwise had the same complete factorial design (burn time × shelter). Across experiments, when at least 50% of all tillers were pre‐reproductive at burn time, either due to shelter treatment or time of year, spring tiller densities were significantly lower than when plants were burned in a more advanced reproductive state. Trends in fall biomass generally followed trends in spring tiller densities, with one exception where plants in no‐shelter plots burned in October had lower biomass than expected based on tiller densities. Treatment responses for the native C4 grass B. laguroides were consistent with those of B. ischaemum. These findings suggest that strategic burns can be used to reduce the subsequent recovery of invasive C4 grasses while not disadvantaging native grasses.
In Situ Coral Nurseries Serve as Genetic Repositories for Coral Reef Restoration after an Extreme Cold‐Water Event
Authors: Schopmeyer Stephanie A. , Lirman Diego , Bartels Erich , Byrne James , Gilliam David S. , Hunt John , Johnson Meaghan E. , Larson Elizabeth A. , Maxwell Kerry , Nedimyer Ken , Walter Cory
Published: October 2011

During an unusual cold‐water event in January 2010, reefs along the Florida Reef Tract suffered extensive coral mortality, especially in shallow reef habitats in close proximity to shore and with connections to coastal bays. The threatened staghorn coral, Acropora cervicornis, is the focus of propagation and restoration activities in Florida and one of the species that exhibited high susceptibility to low temperatures. Complete mortality of wild staghorn colonies was documented at 42.9% of donor sites surveyed after the cold event. Remarkably, 72.7% of sites with complete A. cervicornis mortality had fragments surviving within in situ coral nurseries. Thus, coral nurseries served as repositories for genetic material that would have otherwise been completely lost from donor sites. The location of the coral nurseries at deeper habitats and distanced from shallow nearshore habitats that experienced extreme temperature conditions buffered the impacts of the cold‐water event and preserved essential local genotypes for future Acropora restoration activities.
THE GREEN ALGAL GENUSCLONIOPHORAREPRESENTS A NOVEL LINEAGE IN THE ULVALES: A PROPOSAL FOR CLONIOPHORACEAE FAM. NOV.1
Authors: Carlile Amy L. , O'Kelly Charles J. , Sherwood Alison R.
Published: October 2011

The green algal genusCloniophorahas been classified in the Chaetophorales (Chlorophyceae) based on morphological characters. This study uses DNA sequence data from the nucleus (SSU) and the chloroplast (tufA) from collections in the Hawaiian Islands and a culture originating from Portugal to test this classification. Taxonomic identities of contemporary collections were confirmed by sequencing small fragments of DNA (rbcL and SSU) from type specimens, including the generitype,Cloniophora willeiL. H. Tiffany. These molecular data show thatCloniophoradoes not have close affinities to the Chaetophorales and belongs instead to the Ulvales (Ulvophyceae). The morphological features of eight or more reproductive products per cell and a pyrenoid with a traversing thylakoid membrane support the molecular data and confirm the placement of this group in the Ulvales. As this genus does not belong to any recognized family in the Ulvales, the family Cloniophoraceae, containing the single genusCloniophora, is proposed.
THE INFLUENCE OF SUBMERGED MACROPHYTES ON SEDIMENTARY DIATOM ASSEMBLAGES1
Authors: Vermaire Jesse C. , Prairie Yves T. , Gregory‐Eaves Irene
Published: October 2011

Submerged macrophytes are a central component of lake ecosystems; however, little is known regarding their long‐term response to environmental change. We have examined the potential of diatoms as indicators of past macrophyte biomass. We first sampled periphyton to determine whether habitat was a predictor of diatom assemblage. We then sampled 41 lakes in Quebec, Canada, to evaluate whether whole‐lake submerged macrophyte biomass (BiomEpiV) influenced surface sediment diatom assemblages. A multivariate regression tree (MRT) was used to construct a semiquantitative model to reconstruct past macrophyte biomass. We determined that periphytic diatom assemblages on macrophytes were significantly different from those on wood and rocks (ANOSIM R = 0.63, P < 0.01). A redundancy analysis (RDA) of the 41‐lake data set identified BiomEpiV as a significant (P < 0.05) variable in structuring sedimentary diatom assemblages. The MRT analysis classified the lakes into three groups. These groups were (A) high‐macrophyte, nutrient‐limited lakes (BiomEpiV ≥525 μg · L−1; total phosphorus [TP] <35 μg · L−1; 23 lakes); (B) low‐macrophyte, nutrient‐limited lakes (BiomEpiV <525 μg · L−1; TP <35 μg · L−1; 12 lakes); and (C) eutrophic lakes (TP ≥35 μg · L−1; six lakes). A semiquantitative model correctly predicted the MRT group of the lake 71% of the time (P < 0.001). These results suggest that submerged macrophytes have a significant influence on diatom community structure and that sedimentary diatom assemblages can be used to infer past macrophyte abundance.
Tracking National and Regional Spatial‐Temporal Mortality Risk Associated with NO2 Concentrations in Canada: A Bayesian Hierarchical Two‐Level Model
Authors: Shin Hwashin Hyun , Stieb Dave , Burnett Rick , Takahara Glen , Jessiman Barry
Published: October 2011

The association between daily variations in urban air quality and mortality has been well documented using time series statistical methods. This approach assumes a constant association over time. We develop a space‐time dynamic model that relaxes this assumption, thus more directly examining the hypothesis that improvements in air quality translate into improvements in public health. We postulate a Bayesian hierarchical two‐level model to estimate annual mortality risks at regional and national levels and to track both risk and heterogeneity of risk within and between regions over time. We illustrate our methods using daily nitrogen dioxide concentrations (NO2) and nonaccidental mortality data collected for 1984–2004 in 24 Canadian cities. Estimates of risk and heterogeneity are compared by cause of mortality (cardio‐pulmonary [CP] versus non‐CP) and season, respectively. Over the entire period, the NO2 risk for CP mortality was slightly lower but with a narrower credible interval than that for non‐CP mortality, mainly due to an unusually low risk for a single year (1998). Warm season NO2 risk was higher than cold season risk for both CP and non‐CP mortality. For 21 years overall there were no significant differences detected among the four regional NO2 risks. We found overall that there was no strong evidence for time trends in NO2 risk at national or regional levels. However, an increasing linear time trend in the annual between‐region heterogeneities was detected, which suggests the differences in risk among the four regions are getting larger, and further studies are necessary to understand the increasing heterogeneity.
Electrophysiological Mapping of Embryonic Mouse Hearts: Mechanisms for Developmental Pacemaker Switch and Internodal Conduction Pathway
Authors: YI TONGYIN , WONG JOHNSON , FELLER ERIC , SINK SAMANTHA , TAGHLI‐LAMALLEM OUARDA , WEN JIANYAN , KIM CHANGSUNG , FINK MARTIN , GILES WAYNE , SOUSSOU WALID , CHEN HUEI‐SHENG V.
Published: October 2011

Electrical Mapping of Embryonic Mouse Hearts. Introduction: Understanding sinoatrial node (SAN) development could help in developing therapies for SAN dysfunction. However, electrophysiological investigation of SAN development remains difficult because mutant mice with SAN dysfunctions are frequently embryonically lethal. Most research on SAN development is therefore limited to immunocytochemical observations without comparable functional studies.

Methods and Results: We applied a multielectrode array (MEA) recording system to study SAN development in mouse hearts acutely isolated at embryonic ages (E) 8.5–12.5 days. Physiological heart rates were routinely restored, enabling accurate functional assessment of SAN development. We found that dominant pacemaking activity originated from the left inflow tract (LIFT) region at E8.5, but switched to the right SAN by E12.5. Combining MEA recordings and pharmacological agents, we show that intracellular calcium (Ca2+)‐mediated automaticity develops early and is the major mechanism of pulse generation in the LIFT of E8.5 hearts. Later in development at E12.5, sarcolemmal ion channels develop in the SAN at a time when pacemaker channels are down‐regulated in the LIFT, leading to a switch in the dominant pacemaker location. Additionally, low micromolar concentrations of tetrodotoxin (TTX), a sodium channel blocker, minimally affect pacemaker rhythm at E8.5–E12.5, but suppress atrial activation and reveal a TTX‐resistant SAN‐atrioventricular node (internodal) pathway that mediates internodal conduction in E12.5 hearts.

Conclusions

:
Using a physiological mapping method, we demonstrate that differential mechanistic development of automaticity between the left and right inflow tract regions confers the pacemaker location switch. Moreover, a TTX‐resistant pathway mediates preferential internodal conduction in E12.5 mouse hearts. (J Cardiovasc Electrophysiol, Vol. 23 p. 309‐318, March 2012.)
KCNE5 Polymorphism rs697829 is Associated with QT Interval and Survival in Acute Coronary Syndromes Patients
Authors: PALMER BARRY R. , FRAMPTON C. M. , SKELTON LORRAINE , YANDLE TIM G. , DOUGHTY ROB N. , WHALLEY GILLIAN A. , ELLIS CHRIS J. , TROUGHTON RICHARD W. , RICHARDS A. M. , CAMERON VICKY A.
Published: October 2011

KCNE5 Gene Variant, QTc and Survival in ACS. Introduction: The KCNE family is a group of small transmembrane channel proteins involved in potassium ion (K+) conductance. The X‐linked KCNE5 gene encodes a regulator of the K+ current mediated by the potassium channel KCNQ1. Polymorphisms in KCNE5 have been associated with altered cardiac electrophysiological properties in human studies. We investigated associations of the common rs697829 polymorphism from KCNE5 with baseline characteristics, baseline electrocardiographic (ECG) measurements, and patient survival in a cohort of post‐acute coronary syndromes (ACS) patients (the Coronary Disease Cohort Study cohort).

Methods and Results:
DNA samples (n = 1,740) were genotyped for rs697829 using a TaqMan assay. Baseline ECG data revealed corrected QT (QTc) interval was associated with rs697829 in male, but not female, patients, being extended in the G genotype group (A 416 ± 1.71; G 431 ± 4.25 ms, P = 0.002). Covariate‐adjusted survival was poorest in G genotype patients in Cox proportional hazard modeling of mortality data of males (Poverall= 0.020). Male patients with G genotype had a hazard ratio of 1.44 (1.11–2.33) for death when compared to the A genotype male patients (P = 0.048) after adjustment for age, baseline log‐transformed N‐terminal pro‐B‐type natriuretic peptide (NTproBNP), β‐blocker and insulin treatment, QTc interval, history of myocardial infarction, and physical activity score.

Conclusion:
This study suggests an association between rs697829, a common single nucleotide polymorphism (SNP) from KCNE5, and ECG measurements and survival in postacute ACS patients. Prolonged subclinical QT interval may be a marker of adverse outcome in this group of patients. (J Cardiovasc Electrophysiol, Vol. 23 p. 319‐324, March 2012.)
Natural History of Side Branches Jailed by Drug‐Eluting Stents
Authors: YAMAWAKI MASAHIRO , MURAMATSU TOSHIYA , ARAKI MOTOHARU , HIRANO KEISUKE , NAKANO MASATSUGU , ISHIMORI HIROSHI , ITO YOSHIAKI , MURASATO YOSHINOBU , UENO TAKAFUMI , TSUKAHARA REIKO
Published: October 2011

Background:
 Stent deployment across side branch (SB) ostium is common in daily practice. The present study investigated the natural history of SBs jailed by drug‐eluting stents (DES).

Methods:
 The thrombolysis in myocardial infarction (TIMI) flow grades of 271 consecutive SBs jailed by DES in 196 patients was assessed immediately after the procedure and at 9 months of follow‐up. Patients receiving any SB intervention were excluded.

Results:
 Of 271 jailed SBs, occlusion occurred in 6.27% and deterioration of flow occurred in 6.27% immediately after stenting. In patients with these SB changes, periprocedural myocardial infarction was more likely than in those without (10.0% vs. 1.8%, P = 0.017), while there was no increase of cardiac death or life‐threatening complications such as stent thrombosis and Q‐wave myocardial infarction (Q MI) during follow‐up. At 9 months, angiography showed that one‐third of the initially obstructed SBs were still occluded. In contrast, flow was maintained in almost all (98.6%) SBs with early TIMI flow grade 3 and there was no delayed occlusion of these branches. Multiple regression analysis showed that lesion complexity (Medina bifurcation class, calcification, and preprocedural TIMI grade 2 flow in the SB) and technical factors (jailing by overlapping stents) were related to SB occlusion or flow deterioration.

Conclusions:
 Jailed SBs showing good flow after stenting had a favorable angiographic and clinical outcome after 9 months of follow‐up. However, preprocedural lesion complexity and technical factors should be considered to avoid SB occlusion/flow deterioration associated with periprocedural myocardial infarction. (J Interven Cardiol 2012;25:37–46)
Percutaneous Drainage of Postoperative Pericardial Effusion in Cardiac Surgery
Authors: JAUSSAUD NICOLAS , BOIGNARD AUDE , DURAND MICHEL , BACH VINCENT , PORCU PAOLO , HACINI RACHID , BLIN DOMINIQUE , CHAVANON OLIVIER
Published: October 2011

Background and aim of the study:
 Postoperative pericardial effusion is frequent and can be complicated by cardiac tamponade. Although the different drainage techniques are well described in the setting of medical effusion, there is not a standard postoperative effusion treatment. The aim of this work was to assess the feasibility and effectiveness of the percutaneous pericardial drainage.

Methods:
 This a retrospective study involving 197 patients from 1990 to 2008. Drainage was performed by subxiphoid puncture (91.9%) or left parasternal puncture (8.1%) between 3 and 690 days following a cardiac procedure via median sternotomy. Effusion thickness was at least 10 mm in the subcostal echocardiography view.

Results:
 No deaths directly related to the procedure were observed. Complete and enduring drainage was achieved in 158 patients (80.2%). The procedure failed for 22 patients (11.2%) because no fluid was drained in 14 cases (7.1%) and a right ventricular puncture in 8 cases (4.1%). Recurrence of the effusion, which occurred for 17 patients (8.6%), was more frequent if an effusion of more than 5 mm persisted after the first drainage (P = 0.024) and if the drainage was performed outside the operating room because of emergency (P = 0.046). Risk factors for mortality were recurrence of the effusion (P = 0.04) and drainage performed outside the operating room (P = 0.007).

Conclusions: Percutaneous pericardial drainage is effective to treat postoperative pericardial effusion. When the effusion is thicker than 10 mm and accessible, it can be the initial strategy and surgical drainage can serve as an alternate strategy in case of failure and complications of this procedure. (J Interven Cardiol 2012;25:95–101)
Pooling Designs for Outcomes under a Gaussian Random Effects Model
Authors: Malinovsky Yaakov , Albert Paul S. , Schisterman Enrique F.
Published: October 2011

Summary Due to the rising cost of laboratory assays, it has become increasingly common in epidemiological studies to pool biospecimens. This is particularly true in longitudinal studies, where the cost of performing multiple assays over time can be prohibitive. In this article, we consider the problem of estimating the parameters of a Gaussian random effects model when the repeated outcome is subject to pooling. We consider different pooling designs for the efficient maximum likelihood estimation of variance components, with particular attention to estimating the intraclass correlation coefficient. We evaluate the efficiencies of different pooling design strategies using analytic and simulation study results. We examine the robustness of the designs to skewed distributions and consider unbalanced designs. The design methodology is illustrated with a longitudinal study of premenopausal women focusing on assessing the reproducibility of F2‐isoprostane, a biomarker of oxidative stress, over the menstrual cycle.
A Space–Time Conditional Intensity Model for Invasive Meningococcal Disease Occurrence
Authors: Meyer Sebastian , Elias Johannes , Höhle Michael
Published: October 2011

Summary A novel point process model continuous in space–time is proposed for quantifying the transmission dynamics of the two most common meningococcal antigenic sequence types observed in Germany 2002–2008. Modeling is based on the conditional intensity function (CIF), which is described by a superposition of additive and multiplicative components. As an epidemiological interesting finding, spread behavior was shown to depend on type in addition to age: basic reproduction numbers were 0.25 (95% CI 0.19–0.34) and 0.11 (95% CI 0.07–0.17) for types B:P1.7–2,4:F1–5 and C:P1.5,2:F3–3, respectively. Altogether, the proposed methodology represents a comprehensive and universal regression framework for the modeling, simulation, and inference of self‐exciting spatiotemporal point processes based on the CIF. Usability of the modeling in biometric practice is promoted by an implementation in the R package surveillance.
Tunneled‐cuffed catheter implanted into the accessory hemiazygos vein because of occlusion of the left innominate vein
Authors: Letachowicz Krzysztof , Kołodziej Marian , Międzybrodzki Krzysztof , Letachowicz Waldemar , Weyde Wacław , Sąsiadek Marek , Klinger Marian
Published: October 2011

Hemodialyzed patients are at risk of multiple catheterizations. Nephrologists performing such procedures need to be familiar with congenital and acquired vascular abnormalities. We describe a successful insertion and use of a cuffed‐tunneled catheter in a patient with unusual anatomy of the central venous system. Computed tomography angiography revealed thrombosis of the right subclavian vein and bilateral occlusion of innominate veins. The left internal jugular and subclavian veins joined to form a large vessel that drained through the accessory hemiazygos and azygos veins into the superior vena cava. The catheter was implanted through the left internal jugular vein into the accessory hemiazygos vein. The presented case demonstrates that the catheter can be implanted into distended collateral, especially when no other location is possible.
Acanthamoeba Belonging to T3, T4, and T11: Genotypes Isolated from Air‐Conditioning Units in Santiago, Chile
Authors: Astorga Berbeli , Lorenzo‐Morales Jacob , Martín‐Navarro Carmen M , Alarcón Verónica , Moreno Johanna , González Ana C. , Navarrete Elizabeth , Piñero José E. , Valladares Basilio
Published: October 2011

Free‐living amoebae (FLA) of the genus Acanthamoeba are widely distributed in the environment, in the air, soil, and water, and have also been isolated from air‐conditioning units. The objective of this work was to investigate the presence of this genus of FLA in the air‐conditioning equipment at the Institute of Public Health of Chile in Santiago, Chile. Water and air samples were collected from air‐conditioning systems and were checked for the presence of Acanthamoeba spp. Positive samples were further classified at the genotype level after sequencing the highly variable diagnostic fragment 3 (DF3) region of the 18S rRNA gene. This is the first report of the T3, T4, and T11 genotypes of Acanthamoeba in air‐conditioning units from Chile. Overall, the widespread distribution of potentially pathogenic Acanthamoeba strains in the studied source demands more awareness within the public and health professionals in Chile as this pathogen is emerging as a risk for human health worldwide.
Potential impact of surgical periodontal therapy on oral health‐related quality of life in patients with periodontitis: a pilot study
Authors: Saito Atsushi , Ota Kei , Hosaka Yasuo , Akamatsu Mayako , Hayakawa Hiroki , Fukaya Chie , Ida Atsushi , Fujinami Koushu , Sugito Hiroki , Nakagawa Taneaki
Published: October 2011

Aim

To gain insight into the impact of periodontal surgery on oral health‐related quality of life (QoL) of patients with periodontitis.

Material and Methods

Study participants were recruited from moderate to severe periodontitis patients. After initial periodontal therapy, participants received periodontal surgery. Oral Health‐related Quality of Life Model for Dental Hygiene (OHRQL) was used to assess participant's QoL at each time point of periodontal evaluation (baseline, at least 3 weeks after initial therapy and 3–4 months after surgery).

Results

A total of 21 patients completed OHRQL assessment after surgery. Compared with baseline, a progressive improvement in periodontal parameters was observed during the periodontal therapy. The total mean OHRQL score at baseline (25.5 ± 11.4) was significantly reduced (improved) after initial therapy and after surgery (16.7 ± 9.5 and 15.0 ± 9.7, respectively; p < 0.01). However, no significant difference was found between the OHRQL score after initial therapy and that after surgery.

Conclusions

No significant differences in patients’ oral health‐related QoL were observed between post‐initial therapy and post‐surgery intervals, although a tendency of surgery to determine an improvement in QoL was observed when compared with post‐initial treatment.