bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of diabetes mellitus and metformin use with oncological outcomes of patients with non‐muscle‐invasive bladder cancer
Authors: Rieken Malte , Xylinas Evanguelos , Kluth Luis , Crivelli Joseph J. , Chrystal James , Faison Talia , Lotan Yair , Karakiewicz Pierre I. , Fajkovic Harun , Babjuk Marek , Kautzky‐Willer Alexandra , Bachmann Alexander , Scherr Douglas S. , Shariat Shahrokh F.
Published: September 2013

Objective

To assess the association between diabetes mellitus (DM) and metformin use with prognosis and outcomes of non‐muscle‐invasive bladder cancer (NMIBC)

Patients and Methods

We retrospectively evaluated 1117 patients with NMIBC treated at four institutions between 1996 and 2007.

Cox regression models were used to analyse the association of DM and metformin use with disease recurrence, disease progression, cancer‐specific mortality and any‐cause mortality.

Results

Of the 1117 patients, 125 (11.1%) had DM and 43 (3.8%) used metformin.

Within a median (interquartile range) follow‐up of 64 (22–106) months, 469 (42.0%) patients experienced disease recurrence, 103 (9.2%) experienced disease progression, 50 (4.5%) died from bladder cancer and 249 (22.3%) died from other causes.

In multivariable Cox regression analyses, patients with DM who did not take metformin had a greater risk of disease recurrence (hazard ratio [HR]: 1.45, 95% confidence interval [CI] 1.09–1.94, P = 0.01) and progression (HR: 2.38, 95% CI 1.40‐4.06, P = 0.001) but not any‐cause mortality than patients without DM.

DM with metformin use was independently associated with a lower risk of disease recurrence (HR: 0.50, 95% CI 0.27–0.94, P = 0.03).

Conclusion

Patients with DM and NMIBC who do not take metformin seem to be at an increased risk of disease recurrence and progression; metformin use seems to exert a protective effect with regard to disease recurrence.

The mechanisms behind the impact of DM on patients with NMIBC and the potential protective effect of metformin need further elucidation.
Should centralized histopathological review in penile cancer be the global standard?
Authors: Tang Vincent , Clarke Laurence , Gall Zara , Shanks Jonathan H. , Nonaka Daisuke , Parr Nigel J. , Elliott P. Anthony , Clarke Noel W. , Ramani Vijay , Lau Maurice W. , Sangar Vijay K.
Published: September 2013

Objective

To assess the role of centralized pathological review in penile cancer management.

Materials and Methods

Newly diagnosed squamous cell carcinomas (SCC) of the penis, including squamous cell carcinoma in situ (CIS), from biopsy specimens were referred from 15 centres to the regional supra‐network multidisciplinary team (Sn‐MDT) between 1 January 2008 and 30 March 2011.

Biopsy histology reports and slides from the respective referring hospitals were reviewed by the Sn‐MDT pathologists.

The biopsy specimens’ histological type, grade and stage reported by the Sn‐MDT pathologist were compared with those given in the referring hospital pathology report, as well as with definitive surgery histology.

Any changes in histological diagnosis were sub‐divided into critical changes (i.e. those that could alter management) and non‐critical changes (i.e. those that would not affect management).

Results

A total of 155 cases of squamous cell carcinoma or CIS of the penis were referred from 15 different centres in North‐West England.

After review by the Sn‐MDT, the histological diagnosis was changed in 31% of cases and this difference was statistically significant. A total of 60.4% of the changes were deemed to be critical changes that resulted in a significant change in management.

When comparing the biopsy histology reported by the Sn‐MDT with the final histology from the definitive surgical specimens, a good correlation was generally found.

Conclusions

In the present study a significant proportion of penile cancer histology reports were revised after review by the Sn‐MDT. Many of these changes altered patient management.

The present study shows that accurate pathological diagnosis plays a crucial role in determining the correct treatment and maximizing the potential for good clinical outcomes in penile cancer.

In the case of histopathology, centralization has increased exposure to penile cancer and thereby increased diagnostic accuracy, and should therefore be considered the ‘gold standard’.
Pathogenic variants in non‐protein‐coding sequences
Authors: Makrythanasis P , Antonarakis SE
Published: September 2013

There are approximately 3000 human protein‐coding genes that have been linked with (near) monogenic disorders. This knowledge reflects the past and present focus on protein‐coding genes as the main reservoir of pathogenic variation in the human genome. However, the ‘Medical Genome’ includes all the functional genomic elements for which genotypic variability is a source of pathogenic phenotypes. This short review focuses on examples of pathogenic variants in non‐protein‐coding gene regions. It is likely that the evolving methods of DNA sequencing and functional characterization of the genome will enhance our understanding of the contribution by all functional genomic elements in both Mendelian and complex phenotypes.
Is Marginal Bone Loss around Oral Implants the Result of a Provoked Foreign Body Reaction?
Authors: Albrektsson Tomas , Dahlin Christer , Jemt Torsten , Sennerby Lars , Turri Alberto , Wennerberg Ann
Published: September 2013

Background

When a foreign body is placed in bone or soft tissue, an inflammatory reaction inevitably develops. Hence, osseointegration is but a foreign body response to the implant, which according to classic pathology is a chronic inflammatory response and characterized by bone embedding/separation of the implant from the body.

Purpose

The aim of this paper is to suggest an alternative way of looking at the reason for marginal bone loss as a complication to treatment rather than a disease process.

Materials and Methods

The present paper is authored as a narrative review contribution.

Results

The implant‐enveloping bone has sparse blood circulation and is lacking proper innervation in clear contrast to natural teeth that are anchored in bone by a periodontal ligament rich in blood vessels and nerves. Fortunately, a balanced, steady state situation of the inevitable foreign body response will be established for the great majority of implants, seen as maintained osseointegration with no or only very little marginal bone loss. Marginal bone resorption around the implant is the result of different tissue reactions coupled to the foreign body response and is not primarily related to biofilm‐mediated infectious processes as in the pathogenesis of periodontitis around teeth. This means that initial marginal bone resorption around implants represents a reaction to treatment and is not at all a disease process. There is clear evidence that the initial foreign body response to the implant can be sustained and aggravated by various factors related to implant hardware, patient characteristics, surgical and/or prosthodontic mishaps, which may lead to significant marginal bone loss and possibly to implant failure. Admittedly, once severe marginal bone loss has developed, a secondary biofilm‐mediated infection may follow as a complication to the already established bone loss.

Conclusions

The present authors regard researchers seeing marginal bone loss as a periodontitis‐like disease to be on the wrong track; the onset of marginal bone loss around oral implants depends in reality on a dis‐balanced foreign body response.
Multinucleate cell angiohistiocytoma with hypertrophic nerves
Authors: Doshi‐Chougule Bhavana N. , Gust Alexandra , Mentzel Thomas , Böer‐Auer Almut
Published: September 2013

Multinucleate cell angiohistiocytoma (MCAH) represents a rare benign skin lesion characterized by multiple papules that are usually found on the distal extremities or face of middle‐aged women. We report on a 60‐year‐old male with a history of monoclonal gammopathy and severe rheumatoid arthritis who had several asymptomatic red‐to‐livid papules grouped on the right side of his trunk. The lesions had been present for a few years and were gradually enlarging. Biopsies from three lesions showed a spectrum of changes consisting of a proliferation of small venules together with thickened collagen bundles and increased numbers of interstitial cells including bizarre, multinucleated giant cells. Immunohistochemically, the multinucleated cells were positive for vimentin and lysozyme while the interstitial cells expressed CD68, factor XIIIa and lysozyme. Interestingly, strikingly enlarged dermal nerves were seen in all the three biopsies and two of the biopsies showed an accompanying infiltrate of lymphocytes and plasma cells.
Endgame: engaging the tobacco industry in its own elimination
Authors: Ioannidis John P. A. , Henriksen Lisa , Prochaska Judith J.
Published: September 2013

A billion deaths from tobacco are expected by 2100. Many policy interventions such as increased taxation, restrictions on advertisement, smoking bans, as well as behavioral interventions, such as pharmacological and psychological treatments for smoking cessation, decrease tobacco use, but they reach their limits. Endgame scenarios focusing on tobacco supply rather than demand are increasingly discussed, but meet with resistance by the industry and even by many tobacco control experts. A main stumbling block that requires more attention is what to do with the tobacco industry in endgame scenarios. This industry has employed notoriously talented experts in law, business, organization, marketing, advertising, strategy, policy, and statistics and has tremendous lobbying power. Performance‐based regulatory approaches can pose a legal obligation on manufacturers to decrease – and eventually – eliminate tobacco products according to specified schedules. Penalties and rewards can make such plans both beneficial for public health and attractive to the companies that do the job well. We discuss caveats and reality checks of engaging the tobacco industry to eliminate its current market and change focus. Brainstorming is warranted to entice the industry to abandon tobacco for other profit goals. To get the dialogue started, we propose the wild possibility of hiring former tobacco companies to reduce the costs of healthcare, thereby addressing concurrently two major challenges to public health.
‘Old Wine in Even Newer Bottles’: the uneasy relationship between web 2.0 technologies and European school collaboration
Authors: Gouseti Anastasia
Published: September 2013

The idea of using digital technologies and in particular web 2.0 tools to enhance school collaboration has recently been received with great enthusiasm and a range of new collaborative initiatives has emerged. Through a comparative qualitative case study of four schools in the UK and Greece, this article analyses how online tools are supporting and facilitating school collaboration within the ‘eTwinning’ programme — an EU initiative that seeks to promote web‐based learning and collaboration between schools across Europe. In particular, it examines teachers' and students' compromised experiences of the tech‐based eTwinning projects and highlights the factors that seemed to be undermining collaboration. It analyses whether the implementation of digital technologies for school collaboration has the potential to transform classroom practices or whether existing habits and ‘ways of doing’ are brought into new contexts — leading to another case of ‘the old wine in new bottles’ syndrome often attributed to the use of digital technology in education.
Status epilepticus as a system disturbance: Is status epilepticus due to synchronization or desynchronization?
Authors: Cash Sydney S.
Published: September 2013

The traditional view of seizure activity is one in which there is extreme hypersynchronization. Although what is meant by hypersynchronization is rarely explicitly and fully defined, it can be understood to imply large numbers of neurons firing together essentially simultaneously. In this discussion we explore the possibility that seizures—both self‐terminating and sustained in status—are not purely synchronous in time or in space. We investigate the alternative possibility that much seizure activity represents spatiotemporal desynchronization. Furthermore, we discuss the possibility that, in contrast to canonical views of epileptic activity, a high degree of synchronization is a prerequisite for termination of the seizure rather than a marker of early and ongoing seizure activity. These ideas will be discussed with reference to results from our collaborative group based on microelectrode recordings in patients with epilepsy as well as to the many studies done by others in both patients and animal models. Finally, we will explore implications for these hypotheses in the treatment of patients with epilepsy and in status epilepticus.
Absentee Mothering – Not So Absent? Responses of European Rabbit (Oryctolagus cuniculus) Mothers to Pup Distress Calls
Authors: Rödel Heiko G. , Landmann Christina , Starkloff Anett , Kunc Hansjörg P. , Hudson Robyn
Published: September 2013

Longer‐range acoustic parent‐offspring communication is widespread, but might be absent in species in which young are hidden in burrows during the mother's absence. The European rabbit (Oryctolagus cuniculus) is such a species, with unusually limited maternal care largely restricted to a short daily nursing bout. Based, however, on evidence of frequent infanticide in this species, we hypothesize that rabbits possess a mechanism promoting a maternal response to pup distress calls. We conducted playback experiments with distress calls of pre‐weaning pups played next to the breeding burrows of mothers in a field enclosure (i.e. next to the burrows where mothers give birth and raise their young). Calls were played shortly after pups were born (T1) when infanticide risk is maximal, and shortly before the pups start dispersing from the breeding burrow (T2). A high proportion of mothers (60.6%) responded to pup calls by rapidly returning to their breeding burrow and 40% of them investigated the area around the entrance. Return responses to the playback of pup calls did not differ between mothers during T1 and T2. Thus, our results confirm that rabbit mothers respond rapidly to pup distress calls and that this responsiveness may adaptively serve to repel potentially infanticidal females.
The Impact of Social Capital on the Education of Migrant Children
Authors: Salinas José P.
Published: September 2013

This study used a life‐history qualitative research design to explore social capital within migrant families to understand the impact of social capital on the education of migrant children. The study specifically examined the family culture and the educational experiences of six adult Latinos and/or Latinas who as children followed the migrant stream with their parents to obtain temporary agricultural work. The findings illustrate how social capital was beneficial for student performance in and out of the classroom through intersecting themes and patterns which included consejos, familismo, and compadrazgo. Culturally based recommendations for school leaders and community organizations are presented.
Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization
Authors: Adkins D. E. , McClay J. L. , Vunck S. A. , Batman A. M. , Vann R. E. , Clark S. L. , Souza R. P. , Crowley J. J. , Sullivan P. F. , van den Oord E. J. C. G. , Beardsley P. M.
Published: September 2013

Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In this study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine (MA)‐induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography–mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome‐wide significance threshold (false discovery rate, FDR <0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4‐guanidinobutanoate and pantothenate in stereotypy sensitization, and myo‐inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent MA levels and, with the exception of the myo‐inositol association, suggest a mechanism whereby strain‐based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA‐induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization.
Retrospective Outcome Analyses for Headaches in a Pain Rehabilitation Interdisciplinary Program
Authors: Zheng Yuxi , Tepper Stewart J. , Covington Edward C. , Mathews Manu , Scheman Judith
Published: September 2013

Background

Incapacitating chronic migraine and other severe headaches can have significant impact on peoples' lives, including family and occupational functioning. Although a number of reports have investigated the prevalence and medical treatment of chronic headache, few have reported on the efficacy of treating these disorders within a comprehensive, intensive chronic pain rehabilitation program (CPRP), instead of a headache‐specific program. CPRPs provide treatment of headache by focusing not only on physical pain, but also its association with impaired mood and function.

Methods

We examined the efficacy of CPRP in patients with chronic headache via a retrospective analysis of 123 patients (76.4% female), ages 21 to 85, who completed the CPRP at the Cleveland Clinic between January 2007 and December 2011, and were diagnosed using International Classification of Headache Disorders, 2nd edition and International Classification of Headache Disorders, 2nd edition revision, with migraine or headache as a major complaint. Outcome measures included: pain intensity scores present at the moment of questioning where 10 is the maximal (0‐10/10), Depression Anxiety Stress Scale (DASS) scores, (measuring mood), and Pain Disability Index scores (measuring function). Repeated measures t‐tests were used.

Results

Average pain score on admission was 6.4, and 3.4 upon discharge. Average function on admission was moderately impaired, and normalized on discharge. The average depression score was in the moderate range, and had normalized on discharge. The average anxiety score on admission was in the severe range and was in the mild range on discharge.

Conclusions

Results indicate that individuals had statistically and clinically meaningful improvement in pain, mood, and function. Data suggest that an interdisciplinary CPRP approach for patients diagnosed with headache can be effective in helping to decrease pain, as well as normalize mood and function. Thus, CPRPs serve as an alternative treatment to multidisciplinary headache programs, interventional pain techniques, and primary care standard headache care.
Maternal Butalbital Use and Selected Defects in the National Birth Defects Prevention Study
Authors: Browne Marilyn L. , Van Zutphen Alissa R. , Botto Lorenzo D. , Louik Carol , Richardson Sandra , Druschel Charlotte M.
Published: September 2013

Background

Butalbital is a barbiturate contained in combination products with caffeine and an analgesic prescribed for the treatment of migraine and tension‐type headaches. Controversy exists as to whether butalbital should continue to be prescribed in the United States because of the potential for abuse, overuse headache, and withdrawal syndromes. Butalbital crosses the placenta but there is limited information about potential teratogenicity.

Objective

To evaluate associations between butalbital and a wide range of specific birth defects.

Methods

The National Birth Defects Prevention Study is an ongoing, case–control study of nonsyndromic, major birth defects conducted in 10 states. The detailed case classification and large number of cases in the National Birth Defects Prevention Study allowed us to examine the association between maternal self‐reported butalbital use and specific birth defects. We conducted an analysis of 8373 unaffected controls and 21,090 case infants with estimated dates of delivery between 1997 and 2007; included were birth defects with 250 or more cases. An exploratory analysis examined groups with 100 to 249 cases.

Results

Seventy‐three case mothers and 15 control mothers reported periconceptional butalbital use. Of 30 specific defect groups evaluated, adjusted odds ratios for maternal periconceptional butalbital use were statistically significant for 3 congenital heart defects: tetralogy of Fallot (adjusted odds ratio = 3.04; 95% confidence interval = 1.07−8.62), pulmonary valve stenosis (adjusted odds ratio = 5.73; 95% confidence interval = 2.25−14.62), and secundum‐type atrial septal defect (adjusted odds ratio = 3.06; 95% confidence interval = 1.07−8.79). In the exploratory analysis, an elevated odds ratio was detected for 1 congenital heart defect, single ventricle.

Conclusions

We observed relationships between maternal periconceptional butalbital use and certain congenital heart defects. These associations have not been reported before, and some may be spurious. Butalbital use was rare and despite the large size of the National Birth Defects Prevention Study, the number of exposed case and control infants was small. However, if confirmed in additional studies, our findings will be useful in weighing the risks and benefits of butalbital for the treatment of migraine and tension‐type headaches.
Renal impairment during the treatment of telaprevir with peginterferon and ribavirin in patients with chronic hepatitis C
Authors: Fukuda Kazuto , Imai Yasuharu , Hiramatsu Naoki , Irishio Keiko , Igura Takumi , Sawai Yoshiyuki , Kogita Sachiyo , Makino Yuki , Mizumoto Rui , Matsumoto Yasushi , Nakahara Masanori , Zushi Sinichiro , Kajiwara Nobuyuki , Oze Tsugiko , Kawata Sumio , Hayashi Norio , Takehara Tetsuo
Published: September 2013

Aim

Renal damage has been reported as an important complication during combination treatment of peginterferon (PEG IFN), ribavirin (RBV) and telaprevir (TVR) for chronic hepatitis C. However, very little is known about this complication. We investigated the role TVR plays in renal damage during this triple therapy.

Methods

Twenty‐five chronic hepatitis C patients with genotype 1 and high viral load received TVR in combination with PEG IFN and RBV for 12 weeks followed by treatment with PEG IFN and RBV. Renal function of these patients was prospectively evaluated for 16 weeks.

Results

Creatinine clearance decreased significantly during PEG IFN/RBV/TVR treatment. Consequently, serum creatinine and cystatin C significantly rose during PEG IFN/RBV/TVR treatment. Serum creatinine returned to pretreatment levels after the termination of TVR. The increase of serum creatinine and cystatin C from baseline significantly correlated with serum TVR level at day 7, which was determined by starting dose of TVR per bodyweight . When the patients were classified according to the starting dose of TVR per bodyweight, renal impairment was observed only in the high‐dose (TVR ≥33 mg/kg per day) group, not in the low‐dose (TVR <33 mg/kg per day) group.

Conclusion

These results suggest that TVR dose per bodyweight is important for the occurrence of renal impairment in PEG IFN/RBV/TVR treatment.
Fabrication and characterization of polymer composites for endodontic use
Authors: Alhashimi R. , Mannocci F. , Foxton R. , Deb S.
Published: September 2013

Aim

To develop a low‐density polyethylene–hydroxyapatite (HA‐PE) composite with properties tailored to function as a potential root canal filling material.

Methodology

Hydroxyapatite and polyethylene mixed with strontium oxide as a radiopacifier were extruded from a single screw extruder fitted with an appropriate die to form fibres. The composition of the composite was optimized with clinical handling and placement in the canal being the prime consideration. The fibres were characterized using infrared spectroscopy (FTIR), and their thermal properties determined using differential scanning calorimetry (DSC). The tensile strength and elastic modulus of the composite fibres and gutta‐percha were compared, dry and after 1 month storage in simulated body fluid (SBF), using a universal testing machine. The radiopacity of the fibres was determined using digital radiography. The interaction of the composites with eugenol was evaluated and compared with gutta‐percha. Data of the tensile test were submitted to two‐way anova and Bonferroni tests (P < 0.05).

Results

The endothermic peaks obtained from the DSC studies showed that the melting point of the HA/PE composites ranged between 110.5 and 111.2 °C, whereas gutta‐percha exhibited a melting point at 52 °C. The tensile strength and elastic modulus of the silanated HA/PE composites were significantly higher than those of gutta‐percha (P < 0.0001) under dry conditions and 1 month storage in SBF. The gutta‐percha in eugenol showed a significant increase in the polymer molar mass, whereas the silanated HA/PE composites were unchanged. Radiological evaluations demonstrated that silanated HA/PE fibres were sufficiently radiopaque.

Conclusion

Promising materials for endodontic applications have been developed, offering relevant benefits over the traditional materials in terms of mechanical and chemical properties.
Amphiphilic suramin dissolves Matrigel, causing an ‘inhibition’ artefact within in vitro angiogenesis assays
Authors: Prigozhina Natalie L. , Heisel Andrew J. , Seldeen Jordan R. , Cosford Nicholas D. P. , Price Jeffrey H.
Published: September 2013

The field of study concerning promotion and/or inhibition of angiogenesis has gathered much attention in the scientific community. A great deal of work has been invested towards defining reproducible assays to gauge for promotion or inhibition of angiogenesis in response to drug treatments or growth conditions. Two common components of these assays were noted by our group to have an unexpected and previously unreported interaction. Suramin is a commercially available compound, commonly used as a positive control for in vitro angiogenic inhibition assays. Matrigel is a popular extracellular substrate that supports angiogenic network formation when endothelial cells are cultured on its surface. However, our group demonstrated that suramin alone (without the presence of cells) will actively dissolve Matrigel, causing the extracellular matrix to transition from the gel‐like physical state to a more liquid state. This causes cells on the Matrigel to congregate and sink to the bottom of the well. Therefore, previous observations of inhibition of endothelial cell angiogenesis through the incubation with suramin (including previous observations made by our group) are, largely, an artefact caused by suramin and matrix interaction rather than suramin and cells interaction, as previously reported. Our results suggest that the presence of sulphate groups and amphiphilic properties of suramin are likely responsible for the disruption of the matrix layer. We believe that this information is of prime importance to anyone using similar in vitro models, or employing suramin in any therapy or drug development assays.
God as First Truth, the Will's Good and Faith's Cause: The Theology of Faith and Newman's University Sermons
Authors: McIntosh Mark
Published: September 2013

In the theology of faith, the nature of faith as a human cognitional state is sometimes treated as a foundational topic, to be analysed prior to theological claims about the God who in fact elicits this faith. The article suggests why this is an inadequate account of the act of belief, likely to lead to distortions in the content of belief, and then uses the example of Newman's argument with Lockean notions of faith to propose a renewal of the theology of faith in attention to divine agency.
Seizures during high‐dose antidepressant therapy: a case series with clinical and video‐electroencephalography characteristics
Authors: Ducharlet K. , Seneviratne U. , Sedal L. , Salzberg M. , Cook M. , D'Souza W.
Published: September 2013

This case series identified drug causes of seizures in patients with depressive disorders. Three patients with seizures were admitted for video‐electroencephalography (EEG) monitoring in the context of high‐dose antidepressants and sodium valproate. Very high‐dose antidepressants caused complex partial seizures with secondary generalisation that gave characteristic EEG discharges. This is the first reported series to capture the ictal EEG features associated with antidepressants.
Continuing development of acid pump inhibitors: site of action of pantoprazole.
Authors: Shin JM , Besancon M , Prinz C , Simon A , Sachs G
Published: September 2013

Both receptor antagonists and acid pump inhibitors are clinically useful suppressants of acid secretion. The latter class of drugs, the substituted benzimidazoles, inhibit acid secretion more effectively and, therefore, provide superior symptom relief and healing in all acid‐ related diseases. The H2‐receptor antagonists competitively block the action of histamine on the H2‐receptors of parietal cells. This histamine is released from enterochromaffin‐like cells (ECL cells) due to gastrin, acetylcholine or epinephrine stimulation. In addition, parietal cells have M3‐receptors which can function independently of H2‐ receptors. Hence, there is no single common pathway for parietal cell stimulation. Stimulation of acid secretion by parietal cells requires activation of the acid pump, the gastric H+,K(+)‐ATPase. The target site for the benzimidazoles is the activated gastric H+,K(+)‐ATPase, and, in particular, the cysteines of the pump that are exposed to the acid space of the secretory canaliculus of the parietal cells. Pantoprazole in its protonated form selectively reacts with cysteines present in both the fifth and sixth membrane segments of the ATPase, explaining its mechanism of inhibiting proton transport by this enzyme.
Validation of the Swedish version of the Nursing Delirium Screening Scale used in patients 70 years and older undergoing cardiac surgery
Authors: Lingehall Helena Claesson , Smulter Nina , Engström Karl Gunnar , Gustafson Yngve , Olofsson Birgitta
Published: September 2013

Aims and objectives.  Validation of the Swedish version of the Nursing Delirium Screening Scale as a screening tool for nurses to use to detect postoperative delirium in patients 70 years and older undergoing cardiac surgery.

Background.  Delirium is common among old patients after cardiac surgery. Underdiagnosis and poor documentation of postoperative delirium is problematic, and nurses often misread the signs.

Design.  A prospective observational study.

Methods.  Patients (n = 142) scheduled for cardiac surgery were assessed three times daily by the nursing staff using the Nursing Delirium Screening Scale. Nursing Delirium Screening Scale was compared with the Mini Mental State Examination and the Organic Brains Syndrome Scale, evaluated day one and day four postoperatively. Delirium was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders – DSM‐IV‐TR criteria.

Results.  A larger proportion of patients were diagnosed with delirium according to the Mini Mental State Examination and Organic Brains Syndrome Scale compared with the Nursing Delirium Screening Scale, both on day one and day four. The Nursing Delirium Screening Scale protocol identified the majority of hyperactive and mixed delirium patients, whereas several with hypoactive delirium were unrecognised.

Conclusions.  The Swedish version of the Nursing Delirium Screening Scale was easily incorporated into clinical care and showed high sensitivity in detecting hyperactive symptoms of delirium. However, in the routine use by nurses, the Nursing Delirium Screening Scale had low sensitivity in detecting hypoactive delirium, the most prevalent form of delirium after cardiac surgery. Nursing Delirium Screening Scale probably has to be combined with cognitive testing to detect hypoactive delirium.

Relevance to clinical practice.  Nurses play a key role in detecting delirium. The Nursing Delirium Screening Scale was easy incorporated instrument for clinical practice and identified the majority of hyperactive and mixed delirium, but several of the patients with hypoactive delirium were unrecognised. Training of assessment and cognitive testing seems to be necessary to detect hypoactive delirium.
A Sparse Factor Analytic Probit Model for Congressional Voting Patterns
Authors: Richard Hahn P. , Carvalho Carlos M. , Scott James G.
Published: September 2013

The paper adapts sparse factor models for exploring covariation in multivariate binary data, with an application to measuring latent factors in US Congressional roll-call voting patterns. This straightforward modification provides two advantages over traditional factor analysis of binary data. First, a sparsity prior can be used to assess the evidence that a given factor loading may be exactly 0, realizing a principled unification of exploratory and confirmatory factory analysis. Second, incorporating sparsity into existing factor analytic probit models effects a favourable bias–variance trade-off in estimating the covariance matrix of the multivariate Gaussian latent variables. Posterior summaries from this model applied to the roll-call data provide novel metrics of partisanship of a given Senate.
Classifying Life Course Trajectories: A Comparison of Latent Class and Sequence Analysis
Authors: Barban Nicola , Billari Francesco C.
Published: September 2013

We compare two techniques that are widely used in the analysis of life course trajectories: latent class analysis and sequence analysis. In particular, we focus on the use of these techniques as devices to obtain classes of individual life course trajectories. We first compare the consistency of the classification that is obtained via the two techniques by using a data set on the life course trajectories of young adults. Then, we adopt a simulation approach to measure the ability of these two methods to classify groups of life course trajectories correctly when specific forms of ‘random’ variability are introduced within prespecified classes in an artificial data set. To do so, we introduce simulation operators that have a life course and/or observational meaning. Our results contribute on the one hand to outline the usefulness and robustness of findings based on the classification of life course trajectories through latent class analysis and sequence analysis and on the other hand to illuminate the potential pitfalls in applications of these techniques.
An Application of Semiparametric Bayesian Isotonic Regression to the Study of Radiation Effects in Spaceborne Microelectronics
Authors: Farah Marian , Kottas Athanasios , Morris Robin D.
Published: September 2013

This work is concerned with the vulnerability of spaceborne microelectronics to single-event upset, which is a change of state caused by high-energy charged particles in the solar wind or the cosmic ray environment striking a sensitive node. To measure the susceptibility of a semiconductor device to single-event upsets, testing is conducted by exposing it to high-energy heavy ions or protons produced in a particle accelerator. The number of upsets is characterized by the interaction cross-section, which is an increasing function of linear energy transfer. The prediction of the on-orbit upset rate is made by combining the device geometry and cross-section versus linear energy transfer curve with a model for the orbit-specific radiation environment. We develop a semiparametric isotonic regression method for the upset count responses, based on a Dirichlet process prior for the cross-section curve. The methodology proposed allows the data to drive the shape of the cross-section versus linear energy transfer relationship, resulting in more robust predictive inference for the on-orbit upset rate than conventional models based on Weibull or log-normal parametric forms for the cross-section curve. We illustrate the modelling approach with data from two particle accelerator experiments.
Multivariate Functional Clustering for the Morphological Analysis of Electrocardiograph Curves
Authors: Ieva Francesca , Paganoni Anna M. , Pigoli Davide , Vitelli Valeria
Published: September 2013

Cardiovascular ischaemic diseases are one of the main causes of death all over the world. In this class of pathologies, a quick diagnosis is essential for a good prognosis in reperfusive treatment. In particular, an automatic classification procedure based on statistical analysis of teletransmitted electrocardiograph (‘ECG’) traces would be very helpful for an early diagnosis. This work presents an analysis of ECG traces, either physiological or pathological, of patients whose 12-lead prehospital ECG has been sent to the 118 Dispatch Center in Milan by life-support personnel. The statistical analysis starts with a preprocessing step, where functional data are reconstructed from noisy observations and biological variability is removed by a non-linear registration procedure. Then, a multivariate functional k-means clustering procedure is carried out on reconstructed and registered ECGs and their first derivatives. Hence, a new semi-automatic diagnostic procedure, based solely on the ECG morphology, is proposed to classify ECG traces; finally, the performance of this classification method is evaluated.
Ordinal Latent Variable Models and Their Application in the Study of Newly Licensed Teenage Drivers
Authors: Jackson John C. , Albert Paul S. , Zhang Zhiwei , Simons-Morton Bruce
Published: September 2013

In a unique longitudinal study of teen driving, risky driving behaviour and the occurrence of crashes or near crashes are measured prospectively over the first 18 months of licensure. Of scientific interest is relating the two processes and developing a predictor of crashes from previous risky driving behaviour. In this work, we propose two latent class models for relating risky driving behaviour to the occurrence of a crash or near-crash event. The first approach models the binary longitudinal crash or near-crash outcome by using a binary latent variable which depends on risky driving covariates and previous outcomes. A random-effects model introduces heterogeneity among subjects in modelling the mean value of the latent state. The second approach extends the first model to the ordinal case where the latent state is composed of K ordinal classes. Additionally, we discuss an alternative hidden Markov model formulation. Estimation is performed by using the expectation–maximization algorithm and Monte Carlo expectation–maximization. We illustrate the importance of using these latent class modelling approaches through the analysis of the teen driving behaviour.
Multidimensional Well‐Being at the Top: Evidence for Germany*
Authors: Peichl Andreas , Pestel Nico
Published: September 2013

This paper employs a multidimensional approach for the measurement of well‐being at the top of the distribution using German SOEP micro data. Besides income as the traditional indicator for material well‐being, we include health as a proxy for non‐material quality of life and self‐reported satisfaction with life as dimensions. We find that one‐third of the German population are well off in at least one dimension but only 1 per cent in all three dimensions simultaneously. While the distribution of income has become more concentrated at the top, measures of multidimensional well‐being at the top have decreased slightly over time. Moreover, health and life satisfaction are important drivers of multidimensional richness, which has important policy implications.
Costs of Domestic Violence: A Life Satisfaction Approach*
Authors: Santos Cristina
Published: September 2013

This paper discusses and estimates the costs of domestic violence using a life satisfaction approach. It draws on a British cross‐sectional data set that includes individual self‐reported life satisfaction, household income and experienced domestic violence. The paper estimates the costs of domestic violence as the compensating variation of domestic violence resulting from estimating a life satisfaction regression equation. Some attempts to deal with the problem of self‐selection into abusive relationships and to account for the endogeneity of household income are discussed and implemented. The results suggest that domestic violence is costed very highly by its victims, with estimates ranging from £27,000 to over £70,000. Hence this paper contributes to the literature on valuing non‐marketable goods and discusses the usefulness of a life satisfaction approach when estimating the costs of domestic violence. It claims that, despite its shortcomings, a life satisfaction approach allows for a valuation of domestic violence and answers questions often not answered by other valuation methods.
Electrical Activity of the Crayfish Myocardium
Authors: HERNANDEZ VICENTE , MENDEZ CARLOS
Published: September 2013

Passive and Active Electrical Responses. Introduction: The purpose of this investigation was to study the electrical activity of the crayfish myocardium.

Methods and Results: In isolated crayfish hearts, intracellularly injected hyperpolarizing pulses propagate electrotonically to distances up to 1 mm, and the myocardium behaves as an irregular functional syncytium.

Conclusion: The existence of low‐resistance intercellular connections provides a basis for the analysis and interpretation of many of the results obtained in this article, and makes it possible to propose the following tentative conclusions: (1) in the crayfish myocardium, not all muscle cells are innervated, yet many sites in the crayfish myocardium receive the same polyneural innervation; (2) in many records, the burst of junction potentials that follow each action potential are electrotonic in nature; (3) the cardiac muscle fibers of the crayfish heart are electrically excitable, and the generated action potentials do propagate actively at least for short distances; (4) the gaps between the innervated sites are filled with noninnervated but connected muscle cells that are passively and actively engaged; and (5) an exaggerated richness of innervation is not needed since the crayfish heart can provide effective and quasisynchronous mechanical systoles because of its efficiently combined characteristics.
Atrioventricular Nodal Conduction Rather than Automaticity Determines the Ventricular Rate During Atrial Fibrillation and Atrial Flutter
Authors: VERECKEI ANDRAS , VERA ZAK , PRIDE HARALD P. , ZIPES DOUGLAS P.
Published: September 2013

AV Nodal Conduction During Atrial Fibrillation and Flutter. Introduction: Recent clinical studies have advanced the hypothesis that the atrioventricular (AV) node does not conduct cardiac impulses, but functions as a pacemaker whose discharge rate and rhythm are modulated electrotonically by atrial impulses. Major support for the hypothesis comes from the observation that the short ventricular cycles during atrial fibrillation can be totally eliminated by ventricular pacing at relatively long ventricular cycle lengths.

Methods and Results: The hypothesis was tested in ten anesthetized open chest mongrel dogs with sustained atrial fibrillation or atrial flutter (AF). Large differences (> 120 msec) between the ventricular pacing cycle length that achieved > 95% ventricular capture and the shortest spontaneous RR cycle during AF were considered to be consistent with the modulated AV nodal pacemaker hypothesis, while values ≤ 120 msec were not. The results showed that the ventricular pacing cycle length capturing > 95% of ventricular complexes during AF depended on the spontaneous ventricular rate during AF. Short spontaneous RR cycles during AF required short ventricular pacing cycle lengths to achieve > 95% capture, and the difference between the ventricular pacing cycle length and the shortest spontaneous RR cycle length was narrow, i.e., ≤ 120 msec. Slower ventricular rates could be captured at longer ventricular pacing cycle lengths, and the difference between the ventricular pacing cycle length capturing > 95% of the ventricular complexes and the shortest spontaneous RR interval during AF was large, i.e., > 120 msec. A continuum existed, and values ≤ 120 msec could be transformed to values > 120 msec by increasing vagal intensity to slow the ventricular response. We also found in five dogs that we could not achieve overdrive suppression of automaticity of the putative AV nodal pacemaker focus by ventricular pacing at various cycle lengths and durations during atrial fibrillation.

Conclusion: In conclusion, data from this study fail to support the modulated AV nodal pacemaker hypothesis and are more consistent with conventional concepts of AV nodal conduction.
Slowing of the Atrial Flutter Rate During 1:1 Atrioventricular Conduction in Humans and Dogs: An Effect Mediated Through Atrial Pressure and Volume
Authors: WAXMAN MENASHE B. , KIRSH JOEL A. , YAO LOUIS , CAMERON DOUGLAS A. , ASTA JOHN A.
Published: September 2013

Atrial Flutter Rate and Atrial Pressure. Introduction: During atrial flutter the effects of 1:1 atrioventricular (AV) conduction on the rate of atrial flutter was studied in 12 patients and 14 dogs.

Methods and Results: (A) In all patients, the development of 1:1 AV conduction was associated with a significant increase in flutter cycle length (261.7 ± 9.9 to 281.8 ± 12.1 msec, mean increase 20.3 ± 3.2 msec, P < 0.001). The flutter cycle length returned to control values when 1:1 AV conduction ceased. In four patients in whom atrial pressure was monitored, the prolongation of the atrial flutter cycle interval during 1:1 AV conduction was associated with an immediate rise in atrial pressure (4.0 ± 0.4 to 6.5 ±0.7 mmHg, P < 0.003). (B) In order to examine the mechanism of this phenomenon, similar studies were carried out in dogs with experimentally induced atrial flutter. 1:1 AV conduction consistently lengthened the flutter cycle length during control conditions or following vagotomy and during the administration of isoproterenol. This was always associated with a rise in atrial filling pressure. Inferior vena cava occlusion consistently shortened the flutter cycle length and this was also independent of vagotomy and isoproterenol administration. The atrial filling pressure fell during inferior vena cava occlusion. During 1:1 AV conduction, the prolonged flutter cycle length was shortened by inferior vena cava occlusion to values prior to 1:1 AV conduction.

Conclusion: The rate of atrial flutter is accelerated by reductions in atrial pressure, and slowed by increased atrial pressure. These effects are independent of the vagus nerve or an adrenergic agonist. Changes in atrial pressure and volume affect characteristics of the atrial flutter circuit, and thus can modulate the rate of atrial flutter.