bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inference with Transposable Data: Modelling the Effects of Row and Column Correlations
Authors: Allen Genevera I. , Tibshirani Robert 
Published: March 2012

SummaryWe consider the problem of large-scale inference on the row or column variables of data in the form of a matrix. Many of these data matrices are transposable meaning that neither the row variables nor the column variables can be considered independent instances. An example of this scenario is detecting significant genes in microarrays when the samples may be dependent because of latent variables or unknown batch effects. By modelling this matrix data by using the matrix variate normal distribution, we study and quantify the effects of row and column correlations on procedures for large-scale inference. We then propose a simple solution to the myriad of problems that are presented by unexpected correlations: we simultaneously estimate row and column covariances and use these to sphere or decorrelate the noise in the underlying data before conducting inference. This procedure yields data with approximately independent rows and columns so that test statistics more closely follow null distributions and multiple-testing procedures correctly control the desired error rates. Results on simulated models and real microarray data demonstrate major advantages of this approach: increased statistical power, less bias in estimating the false discovery rate and reduced variance of the false discovery rate estimators.
Increased serum hepcidin levels in patients with porphyria cutanea tarda
Authors: Darwich E. , To‐Figueras J. , Molina‐López R.A. , Deulofeu R. , Olbina G. , Westerman M. , Sánchez‐Tápias J.M. , Muñoz‐Santos C. , Herrero C. 
Published: March 2012

AbstractBackground  Increased iron stores‐ are common in porphyria cutanea tarda (PCT) patients, but the pathophysiological pathways remain unknown. Down‐regulation of hepcidin, a peptide which regulates systemic iron homeostasis, has been demonstrated in different conditions associated with PCT, such as haemochromatosis, chronic hepatitis C (CHC) and excessive alcohol intake. However, serum hepcidin levels have not yet been studied in PCT patients.Objective  To measure the serum hepcidin levels in patients with PCT, CHC and control patients, and to assess the association of hepcidin with serum markers of inflammation, iron overload and oxidative stress.Methods  Hepcidin levels were measured by a competitive enzyme‐linked immunosorbent assay in serum samples of patients presenting PCT (n = 30), CHC (n = 31) and healthy volunteers (n = 52).Results The mean of serum hepcidin levels was significantly higher in the PCT group (129.6 ng/mL) in comparison with the mean values in the CHC (41.3 ng/mL) and control (70.8 ng/mL) groups. The serum concentration of ferritin and interleukin‐6 (IL‐6) was also significantly higher in the PCT group, and correlated strongly with the hepcidin levels. The PCT patients with hepatitis C virus (HCV) infection showed significantly higher hepcidin levels than the group of CHC patients without porphyria.Conclusion  Serum hepcidin levels are increased in patients with PCT suggesting that the mechanisms regulating iron homeostasis in PCT differ from those involved in other related disorders, such as haemochromatosis, HCV infection or alcohol abuse.
Communication skills training for health care professionals improves the adult orthopaedic patient’s experience of quality of care
Authors: Nørgaard Birgitte , Kofoed Poul‐Erik , Ohm Kyvik Kirsten , Ammentorp Jette 
Published: March 2012

Rationale:  Despite the fact that communication has become a core topic in health care, patients still experience the information provided as insufficient or incorrect and a lack of involvement.Objective:  To investigate whether adult orthopaedic patients’ evaluation of the quality of care had improved after a communication skills training course for healthcare professionals.Design and methods:  The study was designed as an intervention study offering professionals training in communicating with patients and colleagues. The outcome was measured by assessing patients’ experience of quality of care. Data were collected by means of a questionnaire and analysed using a linear regression model. Approval was obtained from the Danish Data Protection Agency.Results:  A total of 3133 patients answered the questionnaire, 1279 before staff had attended courses and 1854 in the postcourse period, with response rates of 67.8 and 77.8%, respectively. After the course period, significant increases in responses indicating ‘considerable’ improvement were recorded for 15/19 questions, nonsignificant increases were registered for 3/19 questions and a statistically significant decrease for one question.Study limitations:  This being an effectiveness study, it is deemed that the organizational changes taking place during the study period constitute no serious limitation. Response rates were comparable to those of other studies.Conclusion:  Patients show increased satisfaction with the quality of health care after professionals have attended a communication skills training course, even when implemented in an entire department.Practice implications:  We recommend that healthcare professionals are trained in patient‐centred communication and that training is extended to the entire organization.
Innovations in Practice: Effectiveness of specialist adolescent outreach service for at‐risk adolescents
Authors: Chia Andrew , Assan Ben , Finch Erin , Stargatt Robyn , Burchell Peter , Jones Hayden , Heywood‐Smith Jane 
Published: March 2012

BackgroundOutcomes are reported for an assertive outreach team for adolescents that combines flexible service delivery (e.g. outreach) and broad‐ranging interventions.MethodA retrospective evaluation over a 2‐year period from 30 June 2006 to 30 June 2008 examined rates of hospitalisation, engagement with education and scores on the Child Global Assessment Scale (CGAS).ResultsThe sample showed statistically significant decreases in hospitalisation rates (from 47% to 17%) and increases in engagement with education (full‐time attendance from 23% to 56%). There was a mean increase of 7.4 points on the CGAS.ConclusionAn intensive, flexible and broad‐ranging approach can be applied to adolescents who display at‐risk behaviours and/or have high risk factors for poor long‐term outcome.
Safety and efficacy of targeting platelet proteinase‐activated receptors in combination with existing anti‐platelet drugs as antithrombotics in mice
Authors: Lee H , Sturgeon SA , Mountford JK , Jackson SP , Hamilton JR 
Published: March 2012

BACKGROUND AND PURPOSE Developing novel anti‐platelet strategies is fundamental to reducing the impact of thrombotic diseases. Thrombin activates platelets via proteinase‐activated receptors (PARs), and PAR antagonists are being evaluated in clinical trials for prevention of arterial thrombosis. However, one such trial was recently suspended due to increased bleeding in patients receiving a PAR1 antagonist in addition to anti‐platelet drugs that most often included both aspirin and clopidogrel. Therefore, it remains unclear how to best manipulate PARs for safe antithrombotic activity. To address this, we have examined potential interactions between existing anti‐platelet drugs and strategies that target PARs.EXPERIMENTAL APPROACH We used in vivo mouse models in which interactions between various anti‐platelet strategies could be evaluated. We examined the effects on thrombosis and haemostasis in PAR4−/− mice (platelets unresponsive to thrombin) treated with therapeutic doses of either aspirin or clopidogrel.KEY RESULTS Using a model in which occlusive thrombosis occurred in PAR4−/− mice or wild‐type mice treated with aspirin or clopidogrel, PAR4−/− mice treated with either anti‐platelet agent showed marked protection against thrombosis. This antithrombotic effect occurred without any effect on haemostasis with aspirin, but not clopidogrel. Furthermore, specifically targeting thrombin‐induced platelet activation (via PARs) improved the therapeutic window of non‐specifically inhibiting thrombin functions (via anticoagulants).CONCLUSIONS AND IMPLICATIONS Our results indicate that PAR antagonists used in combination with aspirin provide a potent yet safe antithrombotic strategy in mice and provide insights into the safety and efficacy of using PAR antagonists for the prevention of acute coronary syndromes in humans.
6 Months of “Temporary” Support by Levitronix Left Ventricular Assist Device
Authors: Barbone Alessandro , Malvindi Pietro Giorgio , Sorabella Robert A. , Cortis Graziano , Tosi Paolo F. , Basciu Alessio , Ferrara Pietro , Raffa Giuseppe , Citterio Enrico , Settepani Fabrizio , Ornaghi Diego , Tarelli Giuseppe , Vitali Ettore 
Published: March 2012

AbstractAn otherwise healthy 47‐year‐old man presented to the emergency department in cardiogenic shock after suffering a massive myocardial infarction due to left main occlusion. He was initially supported by extracorporeal membrane oxygenation and subsequently was converted to paracorporeal support with a Levitronix left ventricular assist device. He experienced multiple postoperative complications including renal failure, respiratory failure, retroperitoneal hematoma requiring suspension of anticoagulation, and fungal bloodstream infection precluding transition to an implantable device. He was reconditioned and successfully underwent orthotopic heart transplant 183 days after presentation. A discussion of the relevant issues is included.
Secondarily generalized seizures in temporal lobe epilepsy
Authors: Bone Beata , Fogarasi András , Schulz Reinhard , Gyimesi Csilla , Kalmar Zsuzsanna , Kovacs Norbert , Ebner Alois , Janszky Jozsef 
Published: March 2012

SummaryPurpose:  Secondarily generalized tonic–clonic seizure (SGTCS) may occur rarely in temporal lobe epilepsy (TLE), but SGTCS is the major risk factor for sudden death and for seizure‐related fatal injuries. Our aim was to investigate clinical factors associated with the occurrence of SGTCS in TLE by addressing two questions: (1) What clinical features differentiate patients with TLE who regularly had SGTCS from those who did not? (2) Is there an association of secondarily generalized seizures with preceding seizure elements and clinical data?Methods:  We included 171 patients with TLE (mean age 34.4 ± 10) who participated in our presurgical evaluation program, which included continuous video–electroencephalography (EEG) and magnetic resonance imaging (MRI). Patients had a temporal lobectomy as a result of mesial or neocortical TLE. To reevaluate the archived seizures, we selected the consecutively recorded seizures of each patient. If the patient had more than three recorded seizures, then we reevaluated only the first three. Altogether video‐recorded seizures of 402 patients were reanalyzed.Key Findings:  A positive association between the presence of hippocampal sclerosis on the MRI and SGTCS in the patient history was found, whereas ictal speech and pedal automatism showed a negative association with a SGTCS history. The age of patients showed a positive association, whereas patient’s reactivity before and during the seizure, oral/pedal automatisms, and vocalizations showed a negative association with secondary generalization of a focal‐onset seizure during video‐EEG monitoring.Significance:  Clinical features associated with SGTCS may help clinicians during presurgical monitoring identify high‐risk patients for SGTCS. Our study may help in understanding the pathophysiology of secondary generalization.
The antidepressants citalopram and reboxetine reduce seizure frequency in rats with chronic epilepsy
Authors: Vermoesen Katia , Massie Ann , Smolders Ilse , Clinckers Ralph 
Published: March 2012

SummaryPurpose:  For a long time, antidepressants have been thought to possess proconvulsant properties. This assumption, however, remains controversial, since anticonvulsant effects have been attributed to certain antidepressants. To date, it remains unclear which antidepressants can be used for the treatment of depression in patients with epilepsy. In this respect, studies investigating the convulsant liability of antidepressants in a chronic epilepsy model can give valuable information. The present study was designed to determine the seizure liability of citalopram and reboxetine in the kainic acid–induced post–status epilepticus model for temporal lobe epilepsy.Methods:  Two months after the induction of status epilepticus, chronic epileptic rats (n = 16) were video‐electroencephalography (EEG) monitored during seven consecutive weeks. Weeks 1, 3, 5, and 7 served as sham weeks during which the rats received intraperitoneal saline injections for four consecutive days, followed by a 3‐day sham washout period during which no injections were given. During weeks 2, 4, and 6, rats received intraperitoneal injections with either citalopram (5, 10, and 15 mg/kg, once daily, n = 8) or reboxetine (10, 20, and 30 mg/kg, twice daily, n = 8) for 4 days, again followed by a washout period of 3 days. Drugs were administered in a randomly assigned fixed‐dose regimen per week. Each rat served as its own control. The drug doses were selected based on the doses reported to have antidepressant effects in rats.Key Findings:  Citalopram significantly decreased the spontaneous seizure frequency at the highest dose tested, that is, the mean number of seizures decreased from 12.8 seizures to 8.8 seizures per week (31%) after treatment with 15 mg/kg citalopram. This dose also significantly decreased the cumulative seizure duration. Administration of 5 and 10 mg/kg citalopram did not alter the seizure frequency. The two highest doses of reboxetine significantly decreased the spontaneous seizure frequency, that is, 20 mg/kg reboxetine decreased the seizure frequency from 14.1 to 7.9 (44%) and 30 mg/kg reboxetine decreased the seizure frequency from 11.8 to 7.2 (39%). In addition, both doses significantly decreased the cumulative seizure duration. Administration of 10 mg/kg reboxetine did not alter seizure frequency. Citalopram and reboxetine had no effect on seizure severity and seizure duration in any of the doses tested.Significance:  In general we can conclude that antidepressant doses of citalopram and reboxetine have, depending on the dose, an anticonvulsant effect or no effect on spontaneous seizures in the kainic acid–induced post–status epilepticus rat model.
Endogenous ACh effects on NMDA‐induced interictal‐like discharges along the septotemporal hippocampal axis of adult rats and their modulation by an early life generalized seizure
Authors: Mikroulis Apostolos V. , Psarropoulou Caterina 
Published: March 2012

SummaryPurpose:  Our earlier findings of the modulation of cholinergic neurotransmission by an early life generalized seizure and the reported interaction between muscarinic and N‐methyl‐d‐aspartate (NMDA) receptors prompted us to investigate the effects of endogenous acetylcholine (ACh) on the frequency (Hz) of the epileptiform discharges following NMDA‐receptor activation in the hippocampal slice.Methods:  A sustained (>20 min) generalized convulsion was induced in Sprague‐Dawley juvenile rats by intraperitoneal injection with pentylenetetrazole (PTZ, 70–90 mg/kg) at postnatal day (P) 20. Temporal and septal hippocampal slices were prepared of normal (N) and PTZ‐treated (PTZ) adult (≥P60) rats, and CA3 field potentials were recorded during perfusion with Mg2+‐free artificial cerebrospinal fluid (ACSF) or with ACSF containing 50 μm 4‐aminopyridine (4‐AP).Key Findings:  In Mg2+‐free ACSF, spontaneous interictal‐like epileptiform discharges (IEDs) were recorded in all slices, with significantly higher frequencies in temporal (0.46 ± 0.03 Hz, n = 85) versus septal slices (0.20 ± 0.02 Hz, n = 47, p < 0.000001) but no consistent differences in any other group (i.e., male vs. female or N vs. PTZ). The anticholinesterase eserine (10 μm) increased their frequencies by 150–200% in N‐septal and in all temporal slices and by 300% in PTZ‐septal slices (p = 0.0028). In 60% of the slices the excitatory effect persisted throughout drug perfusion, whereas in the remaining ones it was distinguished in two phases: an early “transient” and a late “steady state.” The steady‐state frequencies resembled the predrug ones in N slices but remained significantly elevated in PTZ slices, especially in the septal group. The muscarinic antagonist atropine (1 μm) decreased IED frequency in all slices (n = 36, p = 0.005) and also fully reversed the eserine effect (n = 38, p < 0.0001). In 4‐AP ACSF, eserine increased spontaneous IED frequency (n = 21) in N and PTZ slices alike; IEDs were subsequently abolished by addition of the NMDA‐receptor antagonist D(−)‐2‐amino‐5‐phosphonopentanoic acid (AP5; 50 μm, n = 6).Significance:  These results demonstrate an intrinsic tonic positive muscarinic acetylcholine receptor (mAChR) contribution to the frequency of NMDA receptor–dependent epileptiform discharges that is amplified following an elevation of endogenous ACh and is more pronounced in the septal hippocampus. Moreover, this positive mAChR contribution to the frequency of IEDs is even more pronounced and persistent in the septal extremity after an early life generalized sustained convulsion. This cholinergic enhancement of the excitatory septal hippocampal output may influence cognitive function and performance, and possibly the adult seizure threshold.
Depressive Symptoms and Subjective and Objective Sleep in Community‐Dwelling Older Women
Authors: Maglione Jeanne E. , Ancoli‐Israel Sonia , Peters Katherine W. , Paudel Misti L. , Yaffe Kristine , Ensrud Kristine E. , Stone Katie L. 
Published: March 2012

ObjectivesTo examine the relationship between depressive symptoms and subjective and objective sleep in older women.DesignCross‐sectional.SettingFour U.S. clinical centers.ParticipantsThree thousand forty‐five community‐dwelling women aged 70 and older.MeasurementsDepressive symptoms were assessed using the Geriatric Depression Scale, categorizing participants as normal (0–2, reference), some depressive symptoms (3–5), or depressed (≥6). Subjective sleep quality and daytime sleepiness were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS). Objective sleep measures were assessed using wrist actigraphy.ResultsIn multivariable‐adjusted models, there were graded associations between greater level of depressive symptoms and worse subjective sleep quality and more subjective daytime sleepiness (P‐trends < .001). Women with some depressive symptoms (odds ratio (OR) = 1.82, 95% confidence interval (CI) = 1.48–2.24) and depressed (OR = 2.84, 95% CI = 2.08–3.86) women had greater odds of reporting poor sleep (PSQI>5). Women with some depressive symptoms (OR = 1.97, 95% CI = 1.47–2.64) and depressed women (OR = 1.70, 95% CI = 1.12–2.58) had greater odds of reporting excessive daytime sleepiness (ESS>10). There were also graded associations between greater level of depressive symptoms and objectively measured wake after sleep onset (WASO) (P‐trend = .03) and wake episodes longer than 5 minutes (P‐trend = .006). Depressed women had modestly higher odds of WASO of 1 hour or longer (OR = 1.37, 95% CI = 1.03–1.83). Women with some depressive symptoms (OR = 1.49, 95% CI = 1.19–1.86) and depressed women (OR = 2.04, 95% CI = 1.52–2.74) had greater odds of being in the highest quartile for number of nap episodes longer than 5 minutes. No associations between depressive symptom level and prolonged sleep latency, poor sleep efficiency, or short or long total sleep time were found.ConclusionGreater depressive symptom levels were associated with more subjective sleep disturbance and objective evidence of sleep fragmentation and napping.
Functional Status After Colon Cancer Surgery in Elderly Nursing Home Residents
Authors: Finlayson Emily , Zhao Shoujun , Boscardin W. John , Fries Brant E. , Landefeld C. Seth , Dudley R. Adams 
Published: March 2012

ObjectivesTo determine functional status and mortality rates after colon cancer surgery in older nursing home residents.DesignRetrospective cohort study.SettingNursing homes in the United States.ParticipantsSix thousand eight hundred twenty‐two nursing home residents aged 65 and older who underwent surgery for colon cancer in the United States between 1999 and 2005.MeasurementsChanges in functional status were assessed before and after surgery using the Minimum Data Set Activity of Daily Living (MDS‐ADL) summary scale, a 28‐point scale in which score increases as functional dependence increases. Regression techniques were used to identify patient characteristics associated with mortality and functional decline 1 year after surgery.ResultsOn average, residents who underwent colectomy had a 3.9‐point worsening in MDS‐ADL score at 1 year. One year after surgery, rates of mortality and sustained functional decline were 53% and 24%, respectively. In multivariate analysis, older age (≥80 vs 65–69, adjusted relative risk (ARR) = 1.53, 95% confidence interval (CI) = 1.15–2.04, P < .001), readmission after surgical hospitalization (ARR = 1.15, 95% CI = 1.03–1.29, P = .02), surgical complications (ARR = 1.11, 95% CI = 1.02–1.21, P = .01), and functional decline before surgery (ARR = 1.21, 95% CI = 1.11–1.32, P < .001) were associated with functional decline at 1 year.ConclusionMortality and sustained functional decline are common after colon cancer surgery in nursing home residents. Initiatives aimed at improving surgical outcomes are needed in this vulnerable population.
Hospital Transfers of Nursing Home Residents with Advanced Dementia
Authors: Givens Jane L. , Selby Kevin , Goldfeld Keith S. , Mitchell Susan L. 
Published: March 2012

ObjectivesTo describe diagnoses and factors associated with hospital transfer in nursing home (NH) residents with advanced dementia.DesignProspective cohort study.SettingTwenty‐two Boston, Massachusetts‐area NHs.ParticipantsThree hundred twenty‐three NH residents with advanced dementia.MeasurementsData were collected quarterly for up to 18 months. Data regarding transfers were collected with regard to hospitalization or emergency department (ED) visit, diagnosis, and duration of inpatient admission. Information on the occurrence of any acute medical event (pneumonia, febrile episode, or other acute illness) in the prior 90 days was obtained quarterly. Logistic regression conducted at the level of the acute medical event identified characteristics associated with hospital transfer.ResultsThe entire cohort experienced 74 hospitalizations and 60 ED visits. Suspected infections were the most common reason for hospitalization (44, 59%), most frequently attributable to a respiratory source (30, 41%). Feeding tube–related complications accounted for 47% of ED visits. In adjusted analysis conducted on acute medical events, younger resident age, event type (pneumonia or other event vs febrile episode), chronic obstructive pulmonary disease, and the lack of a do‐not‐hospitalize (DNH) order (adjusted odds ratio = 5.22, 95% confidence interval = 2.31–11.79) were associated with hospital transfer.ConclusionThe majority of hospitalizations of NH residents with advanced dementia were due to infections and thus were potentially avoidable, because infections are often treatable in the NH. Feeding tube–related complications accounted for almost half of all ED visits, representing a common but underrecognized burden of this intervention. Advance care planning in the form of a DNH order was the only identified modifiable factor associated with avoiding hospitalization.
Producing Evidence of a Miracle: Exemplars of Therapy Conversation With a Survivor of Torture
Authors: Charlés Laurie L. 
Published: March 2012

摘要本文阐述了对一位在祖籍国遭受迫害而移居美国的受折磨幸存者进行治疗案例的结束阶段会面。本文作者使用自然主义范式下的定性研究方法,通过客户对治疗过程的描述与评价考察这名客户的受折磨康复经历案例。本文突出了最后两次会面的对话摘录。在这两次对话中我们透过奇迹问题探讨了客户的过去与未来。本文提出对与这一特定人群的治疗对话作进一步的模态定性分析。