bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-GDBP: a high-level stacked regression model to improve anticancer drug response prediction
Authors: Su Ran , Liu Xinyi , Xiao Guobao , Wei Leyi
Published: February 2019

Anticancer drug response prediction plays an important role in personalized medicine. In particular, precisely predicting drug response in specific cancer types and patients is still a challenge problem. Here we propose Meta-GDBP, a novel anticancer drug-response model, which involves two levels. At the first level of Meta-GDBP, we build four optimized base models (BMs) using genetic information, chemical properties and biological context with an ensemble optimization strategy, while at the second level, we construct a weighted model to integrate the four BMs. Notably, the weights of the models are learned upstream, thus the parameter cost is significantly reduced compared to previous methods. We evaluate the Meta-GDBP on Genomics of Drug Sensitivity in Cancer (GDSC) and the Cancer Cell Line Encyclopedia (CCLE) data sets. Benchmarking results demonstrate that compared to other methods, the Meta-GDBP achieves a much higher correlation between the predicted and the observed responses for almost all the drugs. Moreover, we apply the Meta-GDBP to predict the GDSC-missing drug response and use the CCLE-known data to validate the performance. The results show quite a similar tendency between these two response sets. Particularly, we here for the first time introduce a biological context-based frequency matrix (BCFM) to associate the biological context with the drug response. It is encouraging that the proposed BCFM is biologically meaningful and consistent with the reported biological mechanism, further demonstrating its efficacy for predicting drug response. The R implementation for the proposed Meta-GDBP is available at https://github.com/RanSuLab/Meta-GDBP.
Hemisphere and Gender Differences in the Rich-Club Organization of Structural Networks
Authors: Wang Bin , Zhan Qionghui , Yan Ting , Imtiaz Sumaira , Xiang Jie , Niu Yan , Liu Miaomiao , Wang Gongshu , Cao Rui , Li Dandan
Published: February 2019

Structural and functional differences in brain hemispheric asymmetry have been well documented between female and male adults. However, potential differences in the connectivity patterns of the rich-club organization of hemispheric structural networks in females and males remain to be determined. In this study, diffusion tensor imaging was used to construct hemispheric structural networks in healthy subjects, and graph theoretical analysis approaches were applied to quantify hemisphere and gender differences in rich-club organization. The results showed that rich-club organization was consistently observed in both hemispheres of female and male adults. Moreover, a reduced level of connectivity was found in the left hemisphere. Notably, rightward asymmetries were mainly observed in feeder and local connections among one hub region and peripheral regions, many of which are implicated in visual processing and spatial attention functions. Additionally, significant gender differences were revealed in the rich-club, feeder, and local connections in rich-club organization. These gender-related hub and peripheral regions are involved in emotional, sensory, and cognitive control functions. The topological changes in rich-club organization provide novel insight into the hemisphere and gender effects on white matter connections and underlie a potential network mechanism of hemisphere- and gender-based differences in visual processing, spatial attention and cognitive control.
Acute Inescapable Stress Rapidly Increases Synaptic Energy Metabolism in Prefrontal Cortex and Alters Working Memory Performance
Authors: Musazzi Laura , Sala Nathalie , Tornese Paolo , Gallivanone Francesca , Belloli Sara , Conte Alessandra , Di Grigoli Giuseppe , Chen Fengua , Ikinci Ayşe , Treccani Giulia , Bazzini Chiara , Castiglioni Isabella , Nyengaard Jens R , Wegener Gregers , Moresco Rosa M , Popoli Maurizio
Published: February 2019

Brain energy metabolism actively regulates synaptic transmission and activity. We have previously shown that acute footshock (FS)-stress induces fast and long-lasting functional and morphological changes at excitatory synapses in prefrontal cortex (PFC). Here, we asked whether FS-stress increased energy metabolism in PFC, and modified related cognitive functions. Using positron emission tomography (PET), we found that FS-stress induced a redistribution of glucose metabolism in the brain, with relative decrease of [18F]FDG uptake in ventro-caudal regions and increase in dorso-rostral ones. Absolute [18F]FDG uptake was inversely correlated with serum corticosterone. Increased specific hexokinase activity was also measured in purified PFC synaptosomes (but not in total extract) of FS-stressed rats, which positively correlated with 2-Deoxy [3H] glucose uptake by synaptosomes. In line with increased synaptic energy demand, using an electron microscopy-based stereological approach, we found that acute stress induced a redistribution of mitochondria at excitatory synapses, together with an increase in their volume. The fast functional and metabolic activation of PFC induced by acute stress, was accompanied by rapid and sustained alterations of working memory performance in delayed response to T-maze test. Taken together, the present data suggest that acute stress increases energy consumption at PFC synaptic terminals and alters working memory.
IBD-associated Colon Cancers Differ in DNA Methylation and Gene Expression Profiles Compared With Sporadic Colon Cancers
Authors: Pekow Joel , Hernandez Kyle , Meckel Katherine , Deng Zifeng , Haider Haider I , Khalil Abdurahman , Zhang Chunling , Talisila Nitya , Siva Shivi , Jasmine Farzana , Li Yan Chun , Rubin David T , Hyman Neil , Bissonnette Marc , Weber Christopher , Kibriya Muhammad G
Published: February 2019

Background and Aims

As ulcerative colitis [UC]-associated colorectal cancer [CRC] and sporadic CRC differ in presentation and molecular features, we sought to evaluate differences in the impact of DNA methylation on gene expression.

Methods

DNA methylation was assessed in 11 UC-CRCs and adjacent tissue and 11 sporadic CRCs and adjacent tissue, using Illumina arrays. RNA sequencing was performed on 10 UC-CRCs and adjacent tissue and eight sporadic CRCs and adjacent tissues. Differences in DNA methylation and transcript expression, as well as their correlation in the same tissues, were assessed. Immunohistochemistry was performed for three proteins, ANPEP, FAM92A1, and STK31, all of which exhibited an inverse correlation between DNA methylation and transcript expression in UC.

Results

Thirty three loci demonstrated differences in DNA methylation between UC-CRC and adjacent tissue. In contrast, there were 4204 differentially methylated loci between sporadic colon cancer and adjacent tissue. Eight hundred eighty six genes as well as 10 long non-coding RNAs [lncRNA] were differentially expressed between UC-CRC and adjacent tissues. Although there were no differentially methylated loci between UC and sporadic CRC, 997 genes and 38 lncRNAs were differentially expressed between UC-CRC and sporadic CRC. In UC, 18 genes demonstrated a negative correlation between DNA methylation and transcript expression. Evaluation of protein expression related to three genes, ANPEP, FAM92A1, and STK31, confirmed down-regulation of ANPEP and up-regulation of STK31 in UC-CRC.

Conclusions

Regulation of transcript expression by DNA methylation involves genes key to colon carcinogenesis and may account for differences in presentation and outcomes between inflammatory bowel disease and sporadic colon cancer.
Effectiveness of individual and group multicomponent interventions for smoking cessation in primary care: a quasi-experimental study
Authors: Suárez-Varela Úbeda Juan Fernando , Rodríguez-Vázquez Sara , Ordóñez Barranco José Antonio , Vega Caldera Gilberto , Pérez Alvárez Pedro Pablo , Buitrago Francisco
Published: February 2019

Background

The efficacy of smoking cessation interventions can be quite diverse in day-to-day clinical practice.

Objective

To analyse the effectiveness in smoking cessation of multicomponent interventions carried out in groups or individually in primary care practices.

Methods

A quasi-experimental, multicentre study of 12-month follow-up of patients treated in multicomponent smoking cessation interventions was carried out in Urban health care centres in Sevilla, Spain. Two hundred and twenty smoking patients, ≥18 years of age, participated either in a multicomponent intervention group (n = 145; mean age 51.7 years; 53.1% women) or in individual interventions (n = 77; mean age 50.5 years; 61.0% women). The abstinence or relapse status was computed from patient self-reports, confirmed by relatives or companions when possible and supplemented by CO-oxymetry tests in 89 patients.

Results

The overall percentage of smoking cessation was 36.9% (37.9% with group and 35.1% with individual intervention, P = 0.398). Patients who quit smoking were younger (48.7 versus 52.9 years old, P < 0.01), with fewer years of smoking (32.9 versus 36.8 years, P < 0.05), with higher education (39.0% versus 25.0%, P < 0.05) and had received pharmacological treatment (91.5% versus 67.9%, P < 0.001). In the multivariate analysis, level of education [odds ratio (OR): 1.995; 95% confidence interval (CI): 1.065–3.735, P < 0.01], group intervention (OR: 1.743; 95% CI: 1.006–3.287, P < 0.05) and drug prescription (OR: 2.368; 95% CI: 1.126–4.980, P < 0.05) were significantly associated with smoking cessation.

Conclusions

Our study found that multicomponent group and individual interventions in primary care were associated with an overall quit rate of smoking of 36.9% at 12-month follow-up, with higher probability of success among patients with higher education and those who received the group intervention and drug treatment.
Posaconazole for the treatment of allergic bronchopulmonary aspergillosis in patients with cystic fibrosis
Authors: Periselneris J , Nwankwo L , Schelenz S , Shah A , Armstrong-James D
Published: February 2019

Objectives

Allergic bronchopulmonary aspergillosis (ABPA) can accelerate lung function decline in patients with cystic fibrosis (CF). Antifungal medication can be used in addition to systemic corticosteroid treatment.

Patients and methods

We evaluated Aspergillus-specific IgE and the use of therapeutic drug monitoring of triazoles in a retrospective analysis of 32 patients.

Results

There was a significant reduction in Aspergillus IgE with posaconazole but not with other triazoles (P = 0.026). Aspergillus IgE levels were inversely correlated with the therapeutic drug level of posaconazole.

Conclusions

These data suggest that posaconazole is better than comparator azoles at decreasing serological response to Aspergillus and that this response was better with therapeutic levels of posaconazole.
Structural VARs and the Monetary Transmission Mechanism in Low-Income African Countries†
Authors: Li Bin Grace , Adam Christopher , Berg Andrew , Montiel Peter , O’Connell Stephen
Published: February 2019

Structural Vector Autoregression (SVAR) methods suggest the monetary transmission mechanism may be weak and unreliable in many low-income African countries. But are structural VARs identified via short-run restrictions capable of detecting a transmission mechanism when one exists, under research conditions typical of low-income countries (LICs)? Using a small DSGE as our data-generating process, we assess the impact on VAR-based inference of short data samples, measurement error, high-frequency supply shocks, and other features of the LIC environment. The impact of these features on finite-sample bias appears to be relatively modest when identification is valid—a strong caveat, especially in LICs. Nonetheless many of these features undermine the precision of estimated impulse responses to monetary policy shocks, and cumulatively they suggest that statistically and economically insignificant results can be expected even when the underlying transmission mechanism is strong. These data features not only undermine the efficacy of the SVAR methodology for research and policy-making, but are also severe enough to motivate a continued search for monetary policy rules that are robust to these limitations.
Gastrointestinal Disease in Patients with Common Variable Immunodeficiency: A Retrospective Observational Study
Authors: Khan Rishad , Habbal Mohamad , Scaffidi Michael A , Bukhari Abbas A , Rumman Amir , Al Ghamdi Sarah , Betschel Stephen D , Grover Samir C
Published: February 2019

Background

Gastrointestinal (GI) symptoms are common among patients with common variable immunodeficiency disorder (CVID) yet remain poorly understood.

Aims

The aim of this study was to characterize the demographic, clinical, endoscopic and histologic features of patients with CVID and GI symptoms.

Methods

We conducted a retrospective observational study of all patients with CVID at a large Canadian tertiary care centre between January 2000 and May 2018.

Results

We included 95 patients with CVID. The mean age of patients at the time of CVID diagnosis was 38.2(±16.0). Fifty-three (56%) patients were female. Sixty-four (67%) patients had GI symptoms, with a mean age of onset for GI symptoms of 43.4(±15.1) years. The most common symptoms were bowel movement changes (n = 55 [58%]) and abdominal pain (n = 44 [46%]). Patients with GI symptoms were more likely to have anemia (n = 23 [36%] versus n = 3 [10%], P = 0.0129), iron deficiency (n = 16 [25%] versus n = 2 [7%], P = 0.0481), and have received GI antibiotics (n = 37 [58%] versus n = 0, P < 0.0001) and proton pump inhibitors for reflux (n = 24 [38%] versus n = 3 [10%], P = 0.0067). The most common GI infections were Giardia lamblia (n = 14 [15%]) and Clostridium difficile (n = 4 [4%]). Forty-three (45%) patients with GI symptoms underwent colonoscopy, esophagogastroduodenoscopy or both. The most common findings were inflammation, nodular lymphoid hyperplasia, reduced plasma cells and increased intraepithelial lymphocytes.

Conclusions

This is the largest study on CVID patients in a North American setting. The majority of patients experienced GI symptoms. Future studies should study response to treatment for GI disease among patients with CVID.
Spinal Cord Tethering
Authors: Selden Nathan R.
Published: February 2019

Spinal cord tethering due to a tense filum terminale may present with clinical features that include voiding dysfunction, back and leg pain, musculoskeletal and/or sensorimotor abnormalities of the distal legs and feet, and gait dysfunction. External dysraphic markers may be present over the midline lumbosacral spine, including skin dimples, hemangiomata, atretic tails or skin tags, superficial dermal sinus tracts, and/or bifid or Y-shaped gluteal folds. Magnetic resonance imaging (MRI) remains the most clinically useful and definitive diagnostic modality for tethered spinal cord and should be used to assess the filum terminale, position of the conus tip, and presence of syringomyelia. Spinal cord tethering may be successfully treated with transection of the filum terminale. Careful peri-operative assessment and follow-up of voiding dysfunction and syringomyelia will optimize long-term outcomes.
Lipomyelomeningocele
Authors: Sayama Christina
Published: February 2019

Lipomyelomeningocele (LMMC) is a form of spinal dysraphism involving a lipomatous malformation of the distal spinal cord. Physical examination may reveal cutaneous markers such as subcutaneous fat pads, asymmetric gluteal cleft, atypical dimples, hemangiomas, or atretic tails. A complete work-up should include magnetic resonance imaging to assess the anatomy of the lipomatous malformation, as well as associated findings in the spinal axis such as syringomyelia, Chiari malformation, or additional dysraphic elements. Patients with LMMC carry a high risk for deterioration of urologic and neurologic function. Untethering of the spinal cord and resection of the lipoma should be considered. Difficulties with incision healing, including leakage of cerebrospinal fluid, are common complications of surgical treatment and can be minimized with meticulous closure and close post-operative monitoring.
Spinal Dermal Sinus Tract
Authors: Selden Nathan R.
Published: February 2019

Spinal dermal sinus tract is a rare form of spinal dysraphism that presents occasionally with signs of spinal tethering and rarely with repeated bouts of bacterial meningitis or fulminant pyogenic infection of the conus medullaris or cauda equina leading to serious loss of neurologic function. Physical examination is crucial to accurately diagnose cutaneous findings such as the presence of a pit or tract, in order to avoid subsequent neurological sequelae. Spinal MR imaging is the only definitive imaging modality for the diagnosis of spinal dermal sinus tract and surgical planning for its excision. Total removal of all dermoid tract material is necessary to prevent recurrence. Careful peri-operative assessment and long-term follow-up will optimize outcomes and minimize complications.
Chiari Malformation with Syringomyelia
Authors: Li Yiping , Iskandar Bermans J.
Published: February 2019

Chiari I malformation (CIM) is defined by pathological herniation of the cerebellar tonsils below the foramen magnum. Operative intervention for CIM is generally undertaken to treat neurological deficits associated with tonsillar herniation or with associated syringomyelia. A complete brain and spine MRI is indicated to rule out associated abnormalities and to identify and the presence and extent of syringomyelia. The type of surgical decompression remains controversial but may include bone-only decompression, bony decompression followed by duraplasty, and bony decompression followed by duraplasty and tonsillar shrinkage. Post-operative monitoring for CSF leakage, inadequate decompression, subtle chronic craniocervical instability, and hydrocephalus is critical.
Extratemporal Refractory Epilepsy
Authors: Chavakula Vamsidhar , Park Eun-Hyoung , Madsen Joseph R.
Published: February 2019

Medically refractory epilepsy is defined as the persistence of seizures after appropriate treatment with 2 different medications. A thorough understanding of the clinical history and semiology of seizures is important when considering surgical treatment options, as multifocal epilepsy may not be amenable to resective surgery. Anatomic, functional, and metabolic imaging sequences may assist in identifying a seizure focus, and EEG will provide a functional localization. The surgeon must make a careful and informed decision about the maximal amount of lesion that may be resected without incurring neurologic deficits. Specific postoperative management should be dictated by the natural history of the noted pathology.
Medulloblastoma
Authors: Bruzek Amy K. , Hervey-Jumper Shawn L. , Muraszko Karin M.
Published: February 2019

Medulloblastoma (MB) is the second most common cancer in children and the most common posterior fossa tumor. Presenting symptoms are key to an early diagnosis and may include signs and symptoms of hydrocephalus, cranial neuropathies, ataxia, or nystagmus. MRI of the neuraxis should be completed to aid in operative planning. Preoperative relief of hydrocephalus may be necessary, depending on the patient’s condition. Complete resection is the primary goal, and extent of resection, patient age, ependymal spread, and tumor subtype are all important predictors of overall survival. Spine imaging and lumbar puncture are standard to complete the initial work-up. Chemotherapy and radiation are used for adjuvant therapy after surgical resection. The need for postoperative shunt placement is rare, as most children can be weaned from their ventriculostomy catheters or an endoscopic third ventriculostomy can be performed.
Craniopharyngioma
Authors: Baird Lissa C.
Published: February 2019

Pediatric craniopharyngioma is a histologically benign neoplasm with potential for malignant clinical behavior. Presenting vision and endocrine deficits are common, and the natural history carries unacceptable morbidity, including blindness, complete hypothalamic and pituitary dysfunction, and death. The goal of initial treatment for craniopharyngioma in the pediatric population should be permanent tumor control or cure in order to minimize morbidity from recurrent and progressive disease. Treatment-related morbidity is acute with surgical intervention and requires immediate postoperative endocrinological care. Radiotherapy is associated with delayed treatment morbidity, and long-term monitoring is critical. Inadequate tumor control after initial treatment will result in inevitable recurrence, with more complex and less effective treatment options and higher associated treatment morbidity. Unexpected intraoperative complications can be avoided with careful preoperative planning and good surgical technique.
Middle Fossa Arachnoid Cyst
Authors: Bruzek Amy K. , Maher Cormac O.
Published: February 2019

The middle fossa is the most common location for arachnoid cysts, with approximately 47–55% of all arachnoid cysts occurring in this location. Imaging features of arachnoid cysts are very characteristic and, in general, the diagnosis can be made accurately on the basis of MRI alone. The most likely pathophysiological explanation for arachnoid cysts is a developmental anomaly in splitting of the meningeal membranes. Surgical treatment is recommended for infants with massive cysts and progressive macrocrania, patients with suprasellar arachnoid cysts and obstruction of CSF pathways, and unusual cases where substantial cyst growth occurs or specific neurological signs are present. Cysts may be treated surgically with craniotomy and open fenestration, endoscopic fenestration, or cystoperitoneal shunting. Traumatic tears in the cyst lining may result in subdural hygroma formation, which can lead to increased intracranial pressure.
Posterior Fossa Cyst and Hydrocephalus
Authors: Morone Peter J. , Wellons John C.
Published: February 2019

A Dandy-Walker malformation is an anatomical triad characterized by a large posterior fossa, agenesis of the cerebellar vermis, and dilation of the 4th ventricle. Up to 90% of patients will have hydrocephalus secondary to obstruction of fourth ventricular outflow through the foramen of Luschka and Magendie. The differential diagnosis of Dandy-Walker malformation includes Blake’s pouch cyst, a cystic structure originating within the roof of the 4th ventricle that herniates into the cisterna magna, and posterior fossa arachnoid cysts, which typically displace both the cerebellum and 4th ventricle anteriorly and demonstrate a propensity to enlarge. Brain MRI is the best diagnostic imaging modality to evaluate posterior fossa anatomy and cystic structures. Not all posterior fossa cysts require treatment. Indications for surgical intervention include enlargement, symptomatic mass effect and/or hydrocephalus.
Occipital Encephalocele
Authors: Hubbard Molly , Guillaume Daniel
Published: February 2019

Occipital encephalocele, thought to result from a post-neurulation disorder, is an outpouching of meninges, CSF, and dysplastic brain tissue through a defect in the skull, typically covered by dysplastic skin. While typically diagnosed prenatally with ultrasound, encephaloceles are obvious on physical exam in the post-natal period. Possible associated findings include cranial nerve palsies, blindness, seizures, developmental delay, and/or spasticity. Hydrocephalus may not be present initially but can develop after repair of the encephalocele. Careful study of preoperative MRI/MRA/MRV to evaluate for neurovascular structures or functional tissue is critical to minimize operative complications. A water-tight closure is important to lower the risk of CSF leak and infection. Outcome is related to the amount of tissue within the encephalocele, presence or absence of hydrocephalus, and development of seizures.
Introduction
Authors: Banner Olivia
Published: February 2019

This introduction sets out the rationale and purpose of the volume. Coming from the humanities and the social sciences and based in diverse locations across higher education, scholars arrive to teach health humanities courses equipped with divergent disciplinary and field training and their distinct associated pedagogies; and they are often expected to put that training to distinctly different uses. The introduction discusses ongoing conversations in the medical/health humanities about changes in the field; explains how a focus on pedagogy can advance the field more broadly; and introduces the volume’s chapters, detailing their connections and what contributions they make to developing medical/health humanities as a field.
Shine a Light Here, Dig Deeper Over There
Authors: Haddad Amy M.
Published: February 2019

There are numerous teaching and learning challenges in designing a fully online graduate program in bioethics. In order to ensure student success in any type of online graduate program, courses should be designed so that content is well organized and leads to enduring understanding of essential content. Student understanding in the online environment is uniquely dependent on clear communication of expectations. Content needs to be “chunked” into manageable components and organized so that learning builds throughout a course and program. Finally, online programs need to be humanized so that students are engaged in the course content and with peers and the faculty. One way to humanize online bioethics courses is to consistently integrate the health humanities such as poetry, literature, drama, and film as a means to highlight bioethics content in novel ways or encourage deeper exploration. This chapter describes program and course design for the online environment and uses a specific bioethics program to contextualize how the health humanities are woven through a graduate program. The chapter also provides specific examples of teaching and learning strategies in a clinical bioethics course that incorporates the health humanities. The chapter concludes with a description of emerging findings and broader significance for integrating the health humanities in bioethics education.
Oxford Handbook of Acute Medicine
Authors: Ramrakha Punit , Moore Kevin , Sam Amir
Published: February 2019

This title is a practical and comprehensive guide to the management of the acutely ill patient. It is a single source to the most up-to-date therapies and protocols. It presents the most recent treatment guidelines and evidence-based content that is up-to-date with the recent advances in clinical medicine. Topics covered include cardiac emergencies, respiratory emergencies, gastroenterological emergencies, renal emergencies, shock, neurological emergencies, infectious diseases, emergencies in human immunodeficiency virus, diabetes and endocrine emergencies, haematological emergencies, rheumatological emergencies, dermatological emergencies, psychiatric emergencies, drug overdoses, and practical procedures in acute medicine.
Cardiac emergencies
Authors: Ramrakha Punit S. , Moore Kevin P. , Sam Amir H.
Published: February 2019

This chapter describes cardiac emergencies, including adult life support (basic and advanced), universal treatment algorithm, acute coronary syndrome (ACS), ST-elevation myocardial infarction (STEMI; diagnosis, general measures, reperfusion therapy, thrombolysis, reperfusion by primary percutaneous coronary intervention (PCI), surgery, predischarge risk stratification, complications), ventricular septal defect post-myocardial infarction (MI), atrial tachyarrhythmia post-MI, bradyarrhythmias and indications for pacing, hypotension and shock post-MI, cardiogenic shock, non-ST-elevation MI (NSTEMI; diagnosis, risk stratification, medical management, invasive and non-invasive strategies, discharge, and secondary prevention), arrhythmias, tachyarrhythmias, tachycardia (broad complex, monomorphic, polymorphic, ventricular, narrow complex), atrial fibrillation (AF), atrial flutter, multifocal atrial tachycardia (MAT), accessory pathway tachycardia, atriventricular nodal re-entry tachycardia (AVNRT), bradyarrhythmias, sinus bradycardia, intraventricular conduction disturbances, pulmonary oedema, endocarditis (infective, culture-negative, right-sided, prosthetic valve, prophylaxis), acute aortic regurgitation (AR), acute mitral regurgitation (MR), deep vein thrombosis (DVT), pulmonary embolism (PE), fat embolism, hypertensive emergencies, hypertensive encephalopathy, aortic dissection, acute pericarditis, bacterial pericarditis, cardiac tamponade, and congenital heart disease in adults.
Renal emergencies
Authors: Ramrakha Punit S. , Moore Kevin P. , Sam Amir H.
Published: February 2019

This chapter discusses renal emergencies, including acute kidney injury (AKI), anuria, interstitial nephritis, rhabdomyolysis, hepatorenal syndrome, acute upper urinary tract infections, renal colic and renal stones, haematuria, renovascular disease, cholesterol embolism, and contrast nephropathy.
Infectious diseases
Authors: Ramrakha Punit S. , Moore Kevin P. , Sam Amir H.
Published: February 2019

This chapter explores infectious diseases in acute medicine, including diagnosis of fever in a traveller, malaria, tuberculosis, infections presenting with a fever and rash, primary varicella infection (chickenpox), herpes zoster (shingles), varicella infection control, meningococcal infection, enteric fever (typhoid), viral haemorrhagic fevers, rickettsial infections, Q fever, bites (human and non-human mammalian), infections in intravenous drug users, necrotizing fasciitis, severe acute respiratory syndrome (SARS), and bioterrorism.
Drug overdoses
Authors: Ramrakha Punit S. , Moore Kevin P. , Sam Amir H.
Published: February 2019

This chapter describes drug overdoses, the general approach, and antidotes. It includes information on overdoses of anticonvulsants, antipsychotic drugs, aspirin, benzodiazepines, beta-blockers, calcium channel blockers, carbon monoxide, cyanide, digoxin, ethanol, hypoglycaemic agents, iron, lithium, non-steroidal anti-inflammatory drugs, recreational drugs (stimulants: amphetamines, cocaine; hallucinogens: ketamine, magic mushrooms; depressants: opioids, GHB/GBL), paracetamol, selective serotonin reuptake inhibitors (SSRIs), toxic alcohols, and tricyclic antidepressants.
Incidental solitary pulmonary nodule in an Afro-Caribbean female ex-smoker
Authors: Ainley Adam , Kaneria Sashin , Makker Himender
Published: February 2019

This case study looks at Incidental solitary pulmonary nodule in an ex-smoker Afro-Caribbean lady, and provides questions with model answers.
Impaired vision in an ex-smoker
Authors: Ainley Adam , Makker Himender
Published: February 2019

This case study looks at Impaired vision in an ex-smoker, and provides questions with model answers.
PET-positive right lower lobe mass
Authors: Ainley Adam , Kaneria Sashin , Makker Himender
Published: February 2019

This case study looks at PET positive right lower lobe mass, and provides questions with model answers.
A 30 year old female with a solitary lesion and haemoptysis
Authors: Ainley Adam , Makker Himender
Published: February 2019

This case study looks at A 30 year old lady with solitary lesion and haemoptysis, and provides questions with model answers.
Asymptomatic metastatic disease in a 71 year old male with a history of frequent falls
Authors: Ainley Adam , Makker Himender
Published: February 2019

This case study looks at Asymptomatic metastatic disease in a 71 year man with history of frequent falls, and provides questions with model answers.
A 54 year old patient with T4N2M0 squamous cell carcinoma who developed neutropenic sepsis during the second course of chemotherapy
Authors: Januszewski Adam , Popat Sanjay
Published: February 2019

This case study looks at A 54 year old with T4N2M0 squamous cell carcinoma who developed neutropenic sepsis on second course of chemotherapy, and provides questions with model answers.
A 55 year old female with relapsed stage IV ALK fusion-positive adenocarcinoma treated with crizotinib, presenting with headaches
Authors: Januszewski Adam , Popat Sanjay
Published: February 2019

This case study looks at A 55-year-old patient with relapsed stage IV ALK fusion positive adenocarcinoma treated with crizotinib, presenting with headaches, and provides questions with model answers.
An 84 year old female with advanced staged disease, dementia, and multiple comorbidities presenting with a suspected cancer diagnosis
Authors: Hagena Antke
Published: February 2019

This case study looks at An 84 year old lady with advanced staged disease, dementia and multiple co-morbidities, and provides questions with model answers.
Management of cough, breathlessness, and haemoptysis for a patient who had previous treatment for small-cell lung cancer
Authors: Hagena Antke
Published: February 2019

This case study looks at Patient presenting with cough, breathlessness and haemoptysis, previously resected T1N0MO right upper lobe cancer, and provides questions with model answers.
Constrained Mutational Sampling of Amino Acids in HIV-1 Protease Evolution
Authors: Boucher Jeffrey I , Whitfield Troy W , Dauphin Ann , Nachum Gily , Hollins Carl , Zeldovich Konstantin B , Swanstrom Ronald , Schiffer Celia A , Luban Jeremy , Bolon Daniel N A
Published: February 2019

The evolution of HIV-1 protein sequences should be governed by a combination of factors including nucleotide mutational probabilities, the genetic code, and fitness. The impact of these factors on protein sequence evolution is interdependent, making it challenging to infer the individual contribution of each factor from phylogenetic analyses alone. We investigated the protein sequence evolution of HIV-1 by determining an experimental fitness landscape of all individual amino acid changes in protease. We compared our experimental results to the frequency of protease variants in a publicly available data set of 32,163 sequenced isolates from drug-naïve individuals. The most common amino acids in sequenced isolates supported robust experimental fitness, indicating that the experimental fitness landscape captured key features of selection acting on protease during viral infections of hosts. Amino acid changes requiring multiple mutations from the likely ancestor were slightly less likely to support robust experimental fitness than single mutations, consistent with the genetic code favoring chemically conservative amino acid changes. Amino acids that were common in sequenced isolates were predominantly accessible by single mutations from the likely protease ancestor. Multiple mutations commonly observed in isolates were accessible by mutational walks with highly fit single mutation intermediates. Our results indicate that the prevalence of multiple-base mutations in HIV-1 protease is strongly influenced by mutational sampling.
Role of the Neurosurgeon in Acute Ischemic Stroke Treatment From Triage to Intensive Care Unit
Authors: Kicielinski Kimberly P , Ogilvy Christopher S
Published: February 2019

As ischemic stroke care advances with more patients eligible for mechanical thrombectomy, so too does the role of the neurosurgeon in these patients. Neurosurgeons are an important member of the team from triage through the intensive care unit. This paper explores current research and insights on the contributions of neurosurgeons in care of acute ischemic stroke patients in the acute setting.
Second primary cancers in long-term survivors of glioblastoma
Authors: Kim Jung-Young , Jackman Jennifer G , Woodring Sarah , McSherry Frances , Herndon James E , Desjardins Annick , Friedman Henry S , Peters Katherine B
Published: February 2019

Background

Overall survival (OS) in glioblastoma (GBM) is poor at an average of 14 to 18 months, and long-term survivors (LTS) of GBM are rare. LTS of GBM, defined as surviving >5 years postdiagnosis, represent only 2% to 10% of all GBM patients. LTS of cancer are at high risk of developing second primary neoplasms. This study looks at occurrences of second primary neoplasms in LTS of GBM.

Methods

Records from adult patients newly diagnosed with GBM between January 1, 1998 and February 8, 2010, were retrospectively reviewed to identify LTS, defined as patients who survived ≥5 years. We focused on the identification of a new diagnosis of cancer occurring at least 2 years after the initial GBM diagnosis.

Results

We identified 155 LTS of GBM, with a median OS of 11.0 years (95% CI: 9.0 to 13.1 years) and a median follow-up of 9.6 years (95% CI: 8.7 to 10.7 years). In this cohort of patients, 13 (8.4%) LTS of GBM developed 17 secondary cancers. Eight could potentially be attributed to previous radiation and chemotherapy (skin cancer in radiation field [n = 4], leukemia [n = 2], low-grade glioma [n = 1], and sarcoma of the scalp [n = 1]). The other 9 cases included melanoma (n = 2), prostate cancer (n = 2), bladder cancer (n = 1), endometrioid adenocarcinoma (n = 1), basal cell carcinoma (n = 1), and renal cell carcinoma (n = 1).

Conclusions

Although second primary cancers are rare in GBM LTS, providers should continue close monitoring with appropriate oncologic care. Moreover, this highlights the need for survivorship care of patients with GBM.
Racial Attitudes in America
Authors: Moberg Sarah Patton , Krysan Maria , Christianson Deanna
Published: February 2019

Racial attitudes are multidimensional, and the corresponding picture we get from survey data on racial attitudes is complex. Tracing the results of major national surveys that provide trends over at least 10 years, and with at least three time points (primarily the General Social Survey and the National Election Studies), this article reveals that complexity. Some survey questions show dramatic changes in support of racial equality, while others reveal stagnation or even increasing negativity or disinterest. The article also describes the differences between whites and blacks in patterns and trends. Although compared to some issues, the survey record on racial attitudes is robust and lengthy, we draw attention to important ways in which it is uneven. We conclude by highlighting areas for future research that focus on improved survey measures that will capture more fully the complexity of contemporary public opinion on racial matters.
Group-Based Individualized Comprehensive Core Stability Intervention Improves Balance in Persons With Multiple Sclerosis: A Randomized Controlled Trial
Authors: Arntzen Ellen Christin , Straume Bjørn Kåre , Odeh Francis , Feys Peter , Zanaboni Paolo , Normann Britt
Published: February 2019

Background

Balance and trunk control are often impaired in individuals with multiple sclerosis (MS). Interventions addressing these issues are needed.

Objective

The objective of this study was to compare the immediate and long-term effects of a 6-week individualized, group-based, comprehensive core stability intervention (GroupCoreDIST) with standard care on balance and trunk control in individuals with MS.

Design

This study was a prospective, assessor-masked, randomized controlled trial.

Setting

The GroupCoreDIST intervention was conducted by 6 physical therapists in 6 municipalities in Norway. Standard care included the usual care for individuals with MS in the same municipalities. Assessments at all time points took place at a Norwegian hospital.

Participants

Eighty people with Expanded Disability Status scores of 1 to 6.5 participated in this trial.

Intervention

Randomized, concealed allocation was used to assign the participants to the GroupCoreDIST intervention (n = 40) or to standard care (n = 40). The GroupCoreDIST intervention was conducted with groups of 3 participants (1 group had 4 participants), for 60 minutes 3 times per week.

Measurements

Assessments were undertaken at baseline and at weeks 7, 18, and 30. Outcomes were measured with the Trunk Impairment Scale–Norwegian Version, Mini Balance Evaluation Systems Test, and Patient Global Impression of Change–Balance. Repeated-measures mixed models were used for statistical analysis.

Results

One individual missed all postintervention tests, leaving 79 participants in the intention-to-treat analysis. GroupCoreDIST produced significant between-group effects on the mean difference in the following scores at 7, 18, and 30 weeks: for Trunk Impairment Scale–Norwegian Version, 2.63 points (95% confidence interval [CI] = 1.89–3.38), 1.57 points (95% CI = 0.81–2.33), and 0.95 point (95% CI = 0.19–1.71), respectively; for Mini Balance Evaluation Systems Test, 1.91 points (95% CI = 1.07–2.76), 1.28 points (95% CI = 0.42–2.15), and 0.91 points (95% CI = 0.04–1.77), respectively; and for Patient Global Impression of Change–Balance, 1.21 points (95% CI = 1.66–0.77), 1.02 points (95% CI = 1.48–0.57), and 0.91 points (95% CI = 1.36–0.46), respectively.

Limitations

Groups were not matched for volume of physical therapy.

Conclusions

Six weeks of GroupCoreDIST improved balance and trunk control in the short and long terms compared with standard care in individuals who were ambulant and had MS. The intervention is an effective contribution to physical therapy for this population.
Life below Zero: Bank Lending under Negative Policy Rates
Authors: Heider Florian , Saidi Farzad , Schepens Glenn
Published: February 2019

We show that negative policy rates affect the supply of bank credit in a novel way. Banks are reluctant to pass on negative rates to depositors, which increases the funding cost of high-deposit banks, and reduces their net worth, relative to low-deposit banks. As a consequence, the introduction of negative policy rates by the European Central Bank in mid-2014 leads to more risk-taking and less lending by euro-area banks with a greater reliance on deposit funding. Our results suggest that negative rates are less accommodative and could pose a risk to financial stability, if lending is done by high-deposit banks.

Received April 17, 2018; editorial decision September 18, 2018 by Editor Philip Strahan. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Nurse manager self-reported competency levels
Authors: Flatekval Anne Marie , Corbo Sally Ann
Published: February 2019

The impact of a leadership development program
Selection of Candida albicans Trisomy during Oropharyngeal Infection Results in a Commensal-Like Phenotype
Authors: Forche Anja , Solis Norma V. , Swidergall Marc , Thomas Robert , Guyer Alison , Beach Annette , Cromie Gareth A. , Le Giang T. , Lowell Emily , Pavelka Norman , Berman Judith , Dudley Aimeé M. , Selmecki Anna , Filler Scott G.
Published: February 2019

When the fungus Candida albicans proliferates in the oropharyngeal cavity during experimental oropharyngeal candidiasis (OPC), it undergoes large-scale genome changes at a much higher frequency than when it grows in vitro. Previously, we identified a specific whole chromosome amplification, trisomy of Chr 6 (Chr6x3), that was highly overrepresented among strains recovered from the tongues of mice with OPC. To determine the functional significance of this trisomy, we assessed the virulence of two Chr6 trisomic strains and a Chr5 trisomic strain in the mouse model of OPC. We also analyzed the expression of virulence-associated traits in vitro. All three trisomic strains exhibited characteristics of a commensal during OPC in mice. They achieved the same oral fungal burden as the diploid progenitor strain but caused significantly less weight loss and elicited a significantly lower inflammatory host response. In vitro, all three trisomic strains had reduced capacity to adhere to and invade oral epithelial cells and increased susceptibility to neutrophil killing. Whole genome sequencing of pre- and post-infection isolates found that the trisomies were usually maintained. Most post-infection isolates also contained de novo point mutations, but these were not conserved. While in vitro growth assays did not reveal phenotypes specific to de novo point mutations, they did reveal novel phenotypes specific to each lineage. These data reveal that during OPC, clones that are trisomic for Chr5 or Chr6 are selected and they facilitate a commensal-like phenotype.
Alzheimer’s disease clinical variants show distinct regional patterns of neurofibrillary tangle accumulation
Authors: Petersen Cathrine , Nolan Amber L , de Paula França Resende Elisa , Ehrenberg Alexander , Spina Salvatore , Miller Bruce L. , Seeley William , Miller Zachary , Grinberg Lea T.
Published: February 2019

Background

Neurofibrillary tangle (NFT) pathology in Alzheimer’s disease (AD) follows a stereotypic progression well-characterized by Braak staging. However, some AD cases show deviations from the Braak staging scheme. In this study, we tested the hypothesis that these variations in the regional distribution of tau pathology are linked to heterogeneity in the clinical phenotypes of AD.

Methods

We included a clinicopathological cohort of ninety-four AD cases enriched for atypical clinical presentations. Subjects underwent apolipoprotein E (APOE) genotyping and neuropsychological testing. Main cognitive domains (executive, visuospatial, language, and memory function) were assessed using an established composite z-score. We assessed NFT density and distribution from thioflavin S fluorescent microscopy throughout four neocortical and two hippocampal regions. A mathematical algorithm classifying AD cases into typical, hippocampal sparing (HpSp), and limbic predominant (LP) subtypes based on regional NFT burden was compared to unbiased hierarchical clustering for cases with Braak stage > IV.

Results

Patients diagnosed with logopenic primary progressive aphasia showed significantly higher NFT density in the superior temporal gyrus relative to patients diagnosed with Alzheimer-type dementia (p = 0.0091), while patients with corticobasal syndrome showed significantly higher NFT density in the primary motor cortex (p = 0.0205). Hierarchical clustering identified three discrete clusters of patients characterized respectively by low overall NFT burden (n = 18), high overall burden (n = 30), and cortical-predominant burden (n = 24). A regionally specific effect was observed for visuospatial ability; higher NFT density in the angular gyrus (β = - 0.0921, p = 0.0099) and in the CA1 sector of the hippocampus (β = −0.0735, p = 0.0380) was significantly associated with more severe visuospatial dysfunction, modulated by age of death.

Conclusions

Our results suggest domain-specific functional consequences of regional NFT accumulation. In particular, we observed focal aggregation of NFT density in clinically relevant regions among different clinical AD variants. Continued work to map the regionally specific clinical consequences of tau accumulation presents an opportunity to increase understanding of disease mechanisms underlying atypical clinical manifestations.
Brain-derived circulating cell-free DNA defines the brain region and cell specific origins associated with neuronal atrophy
Authors: Chatterton Zac , Mendelev Natalia , Chen Sean , Raj Towfique , Walker Ruth , Carr Walter , Kamimori Gary , Beeri Michal , Ge Yongchao , Dwork Andrew , Haghighi Fatemeh
Published: February 2019

Liquid biopsies are revolutionizing the fields of prenatal non-invasive testing and cancer diagnosis by leveraging the genetic differences between mother and fetus, and, host and cancer. In the absence of genetic variance, epigenetics has been used to decipher the cell-of-origin of cell-free DNA (cfDNA). Liquid biopsies are minimally invasive and thus represent an attractive option for hard to biopsy tissues such as the brain. Here we report the first evidence of neuron derived cfDNA and cerebellum cfDNA within acute neurotrauma and chronic neurodegeneration, establishing the first class of peripheral biomarkers with specificity for the cell-type and brain-region undergoing potential injury and/or neurodegeneration.