bluuebunny/crossref_metadata_2025 huggingface dataset:
Repression of p63 and induction of EMT by mutant Ras in mammary epithelial cells
Authors: Yoh Kathryn E. , Regunath Kausik , Guzman Asja , Lee Seung-Min , Pfister Neil T. , Akanni Olutosin , Kaufman Laura J. , Prives Carol , Prywes Ron
Published: September 2016

Significance

The oncogenes Harvey Rat Sarcoma Virus GTPase (H-RAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) are well known for altering cell growth and morphology. We show here that they are also able to modify the differentiation state of mammary epithelial cells by inducing an epithelial-to-mesenchymal transition (EMT). This transition leads to greater invasiveness, a hallmark of the progression of tumors toward metastasis. Expression of p63, a protein required for the development of mammary epithelial cells, is strongly repressed by these oncogenes. In turn, loss of p63, which occurs at the transcriptional level, causes a shift in microRNAs and transcription factors that control EMT. Targeting specific genes within this Ras-to-EMT axis may be useful as a therapy to block breast cancer progression.
Innovation network
Authors: Acemoglu Daron , Akcigit Ufuk , Kerr William R.
Published: September 2016

Significance

We describe the strength and importance of the innovation network that links patenting technology fields together. We quantify that technological advances spill out of individual fields and enrich the work of neighboring technologies, but these spillovers are also localized and not universal. Thus, innovation advances in one part of the network can significantly impact nearby disciplines but rarely those very far away. We verify the strength and stable importance of the innovation network by showing how past innovations can predict future innovations in other fields over 10-y horizons. This better understanding of how scientific progress occurs and how inventions build upon themselves is an important input to our depictions of the cumulative process of innovation and its economic growth consequences.
Dual chromatin recognition by the histone deacetylase complex HCHC is required for proper DNA methylation in
Neurospora crassa
Authors: Honda Shinji , Bicocca Vincent T. , Gessaman Jordan D. , Rountree Michael R. , Yokoyama Ayumi , Yu Eun Y. , Selker Jeanne M. L. , Selker Eric U.
Published: September 2016

Significance

Modifications of chromatin proteins (e.g. histones) and DNA play vital roles in genome function. Both hypo- and hypermethylation of DNA are associated with human diseases, including cancers, but the underlying mechanisms are not well understood. Using the filamentous fungus
Neurospora crassa
, one of the simplest eukaryotes with DNA methylation, we report a DNA methylation pathway that depends partially on the histone deacetylase complex HCHC [heterochromatin protein 1 (HP1)–chromodomain protein 2 (CDP-2)–histone deacetylase 1 (HDA-1)– CDP-2/HDA-1–associated protein (CHAP)]. Genome-wide DNA methylation analyses revealed both hypo- and hyper-DNA methylation in strains with defective HCHC components. We show the interrelationship of HCHC components and genetically dissect the proteins to define domains critical for proper DNA methylation and centromeric silencing. This work provides insights into the crosstalk between DNA methylation and histone modifications.
Integrins as architects of cell behavior
Authors: Streuli Charles H.
Published: September 2016

Integrins are cell surface receptors that bind cells to their physical external environment, linking the extracellular matrix to cell function. They are essential in the biology of all animals. In the late 1980s, we discovered that integrins are required for the ability of breast epithelia to do what they are programmed to do, which is to differentiate and make milk. Since then, integrins have been shown to control most other aspects of phenotype: to stay alive, to divide, and to move about. Integrins also provide part of the mechanism that allows cells to form tissues. Here I discuss how we discovered that integrins control mammary gland differentiation and explore the role of integrins as central architects of other aspects of cell behavior.
Tay–Sachs disease mutations in HEXA target the α chain of hexosaminidase A to endoplasmic reticulum–associated degradation
Authors: Dersh Devin , Iwamoto Yuichiro , Argon Yair
Published: September 2016

Loss of function of the enzyme β-hexosaminidase A (HexA) causes the lysosomal storage disorder Tay–Sachs disease (TSD). It has been proposed that mutations in the α chain of HexA can impair folding, enzyme assembly, and/or trafficking, yet there is surprisingly little known about the mechanisms of these potential routes of pathogenesis. We therefore investigated the biosynthesis and trafficking of TSD-associated HexA α mutants, seeking to identify relevant cellular quality control mechanisms. The α mutants E482K and G269S are defective in enzymatic activity, unprocessed by lysosomal proteases, and exhibit altered folding pathways compared with wild-type α. E482K is more severely misfolded than G269S, as observed by its aggregation and inability to associate with the HexA β chain. Importantly, both mutants are retrotranslocated from the endoplasmic reticulum (ER) to the cytosol and are degraded by the proteasome, indicating that they are cleared via ER-associated degradation (ERAD). Leveraging these discoveries, we observed that manipulating the cellular folding environment or ERAD pathways can alter the kinetics of mutant α degradation. Additionally, growth of patient fibroblasts at a permissive temperature or with chemical chaperones increases cellular Hex activity by improving mutant α folding. Therefore modulation of the ER quality control systems may be a potential therapeutic route for improving some forms of TSD.
Functional nanoscale coupling of Lyn kinase with IgE-FcεRI is restricted by the actin cytoskeleton in early antigen-stimulated signaling
Authors: Shelby Sarah A. , Veatch Sarah L. , Holowka David A. , Baird Barbara A.
Published: September 2016

The allergic response is initiated on the plasma membrane of mast cells by phosphorylation of the receptor for immunoglobulin E (IgE), FcεRI, by Lyn kinase after IgE-FcεRI complexes are cross-linked by multivalent antigen. Signal transduction requires reorganization of receptors and membrane signaling proteins, but this spatial regulation is not well defined. We used fluorescence localization microscopy (FLM) and pair-correlation analysis to measure the codistribution of IgE-FcεRI and Lyn on the plasma membrane of fixed cells with 20- to 25-nm resolution. We directly visualized Lyn recruitment to IgE-FcεRI within 1 min of antigen stimulation. Parallel FLM experiments captured stimulation-induced FcεRI phosphorylation and colocalization of a saturated lipid-anchor probe derived from Lyn’s membrane anchorage. We used cytochalasin and latrunculin to investigate participation of the actin cytoskeleton in regulating functional interactions of FcεRI. Inhibition of actin polymerization by these agents enhanced colocalization of IgE-FcεRI with Lyn and its saturated lipid anchor at early stimulation times, accompanied by augmented phosphorylation within FcεRI clusters. Ising model simulations provide a simplified model consistent with our results. These findings extend previous evidence that IgE-FcεRI signaling is initiated by colocalization with Lyn in ordered lipid regions and that the actin cytoskeleton regulates this functional interaction by influencing the organization of membrane lipids.
Molecular signatures of mu opioid receptor and somatostatin receptor 2 in pancreatic cancer
Authors: Jorand Raphael , Biswas Sunetra , Wakefield Devin L. , Tobin Steven J. , Golfetto Ottavia , Hilton Kelsey , Ko Michelle , Ramos Joe W. , Small Alexander R. , Chu Peiguo , Singh Gagandeep , Jovanovic-Talisman Tijana
Published: September 2016

Pancreatic ductal adenocarcinoma (PDAC), a particularly aggressive malignancy, has been linked to atypical levels, certain mutations, and aberrant signaling of G-protein–coupled receptors (GPCRs). GPCRs have been challenging to target in cancer because they organize into complex networks in tumor cells. To dissect such networks with nanometer-scale precision, here we combine traditional biochemical approaches with superresolution microscopy methods. A novel interaction specific to PDAC is identified between mu opioid receptor (MOR) and somatostatin receptor 2 (SSTR2). Although MOR and SSTR2 did not colocalize in healthy pancreatic cells or matching healthy patient tissues, the pair did significantly colocalize in pancreatic cancer cells, multicellular tumor spheroids, and cancerous patient tissues. Moreover, this association in pancreatic cancer cells correlated with functional cross-talk and increased metastatic potential of cells. Coactivation of MOR and SSTR2 in PDAC cells led to increased expression of mesenchymal markers and decreased expression of an epithelial marker. Together these results suggest that the MOR-SSTR2 heteromer may constitute a novel therapeutic target for PDAC.
The Value of Heterogeneous Property Rights and the Costs of Water Volatility
Authors: Brent Daniel A.
Published: September 2016

The system of prior appropriation in the Western Unites States prioritizes property rights for water based on the establishment of beneficial use, creating a hierarchy where rights initiated first are more secure. I estimate the demand for security in water rights through their capitalization in agricultural property markets in the Yakima River Basin, a major watershed in Washington State. All water rights are satisfied in an average year, so the relative value of secure property rights is a function of water supply volatility and the costs of droughts are predominantly born by those with weak rights. In aggregate, security in water rights does not capitalize into property values at the irrigation district level; however, there is heterogeneity in the premium for secure water rights. The lack of a premium for district‐level water security is robust to a variety of econometric methods to account for correlated district unobservables, and the null result produces an economically significant upper bound on the value to water security for the district. The ability for farmers to adapt to water supply volatility, as well as expectations about water markets and government infrastructure investment, are leading explanations for the lack of an aggregate premium. These explanations are supported by the pattern of heterogeneity in the water security premium.
Endogenous Risk and Point‐Nonpoint Uncertainty Trading Ratios
Authors: Horan Richard D. , Shortle James S.
Published: September 2016

Point‐nonpoint trading enables highly uncertain nonpoint pollution abatement to be substituted for relatively certain point source pollution abatement. Market designers use uncertainty trade ratios to address imperfect substitution between these commodities. Guidance from government agencies and other entities recommends large ratios that penalize trades for nonpoint abatement, and extant programs universally implement this guidance. Previous research has shown that the standard guidance is based on an inappropriate framing of the risk effects of substituting nonpoint for point source pollution abatement, and has demonstrated that the trade ratios should be set to encourage or discourage substitution, depending on whether the substitution is risk‐reducing or risk‐increasing. However, the Pigouvian pricing approach used to develop this result obscures the underlying economic calculus because it does not recognize or characterize the tradeoffs between abatement costs savings and environmental risk that must be considered in an economic evaluation of alternative ratios, and that would be key to explaining why ratios recommended by economic analysis would be preferred to received wisdom. We develop a new approach that explicitly identifies and characterizes the tradeoffs associated with the choice of ratio. The approach is examined both in first‐best settings where trade ratios and initial permit allocations are jointly determined, and in second‐best settings where permit allocations are taken as given. We provide a numerical analysis of trading in the Susquehanna River Basin in Pennsylvania to illustrate theory. We find theoretical and numerical support suggesting that smaller ratios may be optimal.
Price Elasticity of Groundwater Demand: Attenuation and Amplification Bias Due to Incomplete Information
Authors: Mieno Taro , Brozović Nicholas
Published: September 2016

Measurement errors in both human and natural components of agricultural and environmental systems can be as much a source of estimation bias as omitted variables, selfselection, simultaneity, and reverse causality. Nonetheless, partly because of difficulties in obtaining data, there is less literature on measurement error problems than on other endogeneity problems. This article examines estimation bias in the price elasticity of groundwater consumption for irrigated agriculture on the intensive margin. The price at issue is for the energy used in pumping and pressurizing water for delivery. Lacking the precise unit irrigation cost, previous studies imputed irrigation costs. We first consider groundwater irrigation costs and identify factors that can cause measurement errors in the process of imputation under incomplete information about the determinants of irrigation costs. We follow this by systematically analyzing the potential bias caused by measurement errors, using econometric theory along with Monte Carlo simulations where appropriate. We then quantify actual measurement errors, making use of a unique dataset in which energy and groundwater consumption data are matched for individual observations. Finally, we compare regression results using exact irrigation costs as opposed to imputed ones. We find evidence of substantial measurement errors resulting in attenuation and amplification bias in the price elasticity of irrigation water consumption on the intensive margin. Our results indicate that measurement errors in irrigation costs can lead to misleading policy implications related to water and energy pricing as a tool to conserve water. We also show that estimating the energy price elasticity of groundwater use is not as straightforward as previously thought.
State aggregation for fast likelihood computations in molecular evolution
Authors: Davydov Iakov I , Robinson-Rechavi Marc , Salamin Nicolas
Published: September 2016

Motivation

Codon models are widely used to identify the signature of selection at the molecular level and to test for changes in selective pressure during the evolution of genes encoding proteins. The large size of the state space of the Markov processes used to model codon evolution makes it difficult to use these models with large biological datasets. We propose here to use state aggregation to reduce the state space of codon models and, thus, improve the computational performance of likelihood estimation on these models.

Results

We show that this heuristic speeds up the computations of the M0 and branch-site models up to 6.8 times. We also show through simulations that state aggregation does not introduce a detectable bias. We analyzed a real dataset and show that aggregation provides highly correlated predictions compared to the full likelihood computations. Finally, state aggregation is a very general approach and can be applied to any continuous-time Markov process-based model with large state space, such as amino acid and coevolution models. We therefore discuss different ways to apply state aggregation to Markov models used in phylogenetics.

Availability and Implementation

The heuristic is implemented in the godon package (https://bitbucket.org/Davydov/godon) and in a version of FastCodeML (https://gitlab.isb-sib.ch/phylo/fastcodeml).

Supplementary information

Supplementary data are available at Bioinformatics online.
Measuring Appropriate Antimicrobial Use: Attempts at Opening the Black Box
Authors: Spivak Emily S. , Cosgrove Sara E. , Srinivasan Arjun
Published: September 2016

Indiscriminate antimicrobial use has plagued medicine since antibiotics were first introduced into clinical practice >70 years ago. Infectious diseases physicians and public health officials have advocated for preservation of these life-saving drugs for many years. With rising burden of antimicrobial-resistant organisms and Clostridium difficile infections, halting unnecessary antimicrobial use has become one of the largest public health concerns of our time. Inappropriate antimicrobial use has been quantified in various settings using numerous definitions; however, no established reference standard exists. With mounting national efforts to improve antimicrobial use, a consensus definition and standard method of measuring appropriate antimicrobial use is imperative. We review existing literature on systematic approaches to define and measure appropriate antimicrobial use, and describe a collaborative effort at developing standardized audit tools for assessing the quality of antimicrobial prescribing.
Evaluating total uncertainty for biomass- and abundance-at-age estimates from eastern Bering Sea walleye pollock acoustic-trawl surveys
Authors: Woillez Mathieu , Walline Paul D. , Ianelli James N. , Dorn Martin W. , Wilson Christopher D. , Punt Andre E.
Published: September 2016

A comprehensive evaluation of the uncertainty of acoustic-trawl survey estimates is needed to appropriately include them in stock assessments. However, this evaluation is not straightforward because various data types (acoustic backscatter, length, weight, and age composition) are combined to produce estimates of abundance- and biomass-at-age. Uncertainties associated with each data type and those from functional relationships among variables need to be evaluated and combined. Uncertainty due to spatial sampling is evaluated using geostatistical conditional (co-) simulations. Multiple realizations of acoustic backscatter were produced using transformed Gaussian simulations with a Gibbs sampler to handle zeros. Multiple realizations of length frequency distributions were produced using transformed multivariate Gaussian co-simulations derived from quantiles of the empirical length distributions. Uncertainty due to errors in functional relationships was evaluated using bootstrap for the target strength-at-length and the weight-at-length relationships and for age–length keys. The contribution of each of these major sources of uncertainty was assessed for acoustic-trawl surveys of walleye pollock in the eastern Bering Sea in 2006–2010. This simulation framework allows a general computation for estimating abundance- and biomass-at-age variance–covariance matrices. Such estimates suggest that the covariance structure assumed in fitting stock assessment models differs substantially from what careful analysis of survey data actually indicate.
A retrospective comparison of outcome and toxicity of preoperative image-guided intensity-modulated radiotherapy versus conventional pelvic radiotherapy for locally advanced rectal carcinoma
Authors: Huang Chun-Ming , Huang Ming-Yii , Tsai Hsiang-Lin , Huang Ching-Wen , Ma Cheng-Jen , Lin Chih-Hung , Huang Chih-Jen , Wang Jaw-Yuan
Published: September 2016

The aim of the study was to compare clinical outcomes and toxicity between 3D conformal radiotherapy (3DCRT) and image-guided intensity-modulated radiotherapy (IG-IMRT) administered through helical tomotherapy in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy. We reviewed 144 patients with Stage II–III rectal cancer receiving preoperative fluoropyrimidine-based chemoradiotherapy followed by radical resection. Tumor responses following chemoradiotherapy were evaluated using the Dworak tumor regression grade (TRG). Of the 144 patients, 45 received IG-IMRT and 99 received 3DCRT. A significant reduction in Grade 3 or 4 acute gastrointestinal toxicity (IG-IMRT, 6.7%; 3DCRT, 15.1%; P = 0.039) was observed by IG-IMRT. The pathologic complete response (pCR) rate did not differ between the IG-IMRT and the 3DCRT group (17.8% vs 15.1%, P = 0.52). Patients in the IG-IMRT group had the trend of favorable tumor regressions (TRG 3 or 4) compared with those in the 3DCRT group (66.7% vs 43.5%, P = 0.071). The median follow-up was 53 months (range, 18–95 months) in the 3DCRT group and 43 months (range, 17–69 months) in the IG-IMRT group. Four-year overall, disease-free, and local failure–free survival rates of the IG-IMRT and 3DCRT groups were 81.6% and 67.9% (P = 0.12), 53.8% and 51.8% (P = 0.51), and 88% and 75.1% (P = 0.031), respectively. LARC patients treated with preoperative IG-IMRT achieved lower acute gastrointestinal adverse effects and a higher local control rate than those treated with 3DCRT, but there was no prominent difference in distant metastasis rate and overall survival between two treatment modalities.
Acceptance and Commitment Therapy for Posttraumatic Stress Disorder
Authors: Scarlet Janina , Lang Ariel J. , Walser Robyn D.
Published: September 2016

This chapter examines evidence for the effectiveness of complementary and alternative medicine (CAM) for posttraumatic stress disorder (PTSD). There is high demand for CAM among both military and civilian consumers and thus CAM for PTSD warrants thorough analysis. The CAM interventions reviewed herein include mindfulness and other meditative practices, acupuncture, yoga, relaxation, breathing training, and physical exercise. Although there are few rigorous studies of CAM for PTSD, available evidence suggests that these approaches are moderately effective. They would generally not be considered a first line intervention for PTSD at this point, but rather would be recommended as an adjunct to established approaches. The limited number of studies available, however, precludes drawing firm conclusions. Thus, future work should focus on better understanding the optimal uses of CAM for PTSD.
Alternative Medicine Pharmacology
Authors: McLay Robert N. , Miletich Derek M. , Brown Nathaniel A. , Ross Lesley
Published: September 2016

To many systems of thinking, pharmacology is, by definition, not alternative medicine. However, many alternative treatments, such as the use of herbal compounds or illicit drugs to help PTSD, are outside the scope of standard medicine yet rely on pharmacological mechanisms to support their use. In this chapter, concepts for non-traditional uses of chemical compounds are reviewed. Alternative uses of specific compounds are described. This includes: atypical uses of allopathic compounds, the use of synthetically imitated or isolated natural compounds, the pharmacology of plant-based and herbal medications, and the use of illicit substances which are normally banned in the United States.
Canines as Assistive Therapy for Treatment of PTSD
Authors: Ritchie Elspeth Cameron , Chumley Perry R. , Olmert Meg Daley , Yount Rick A. , Laurent Matthew St. , Rumayor Christina
Published: September 2016

Canine-assisted therapies are being used increasingly both by veterans and the civilian community for mental and emotional support. During the past decade, a growing body of scientific research has provided evidence that human–animal interactions can improve social competence and reduce physiological, psychological, and behavioral effects of stress and social isolation. One meta-analysis that evaluated 49 published studies of animal-assisted therapy (AAT), used mainly to target mental health concerns, concluded that AAT is effective for medical well-being, for behavioral outcomes in adults, and for improving the therapy participation of children with autism and related disorders. The study also found that AAT was as effective as other interventions examined in comparison.
Cervical Spine Imaging in Blunt Trauma Patients
Authors: Lee Christoph I.
Published: September 2016

This chapter, found in the back pain section of the book, provides a succinct synopsis of a key study examining the use of cervical spine imaging in blunt trauma patients. This summary outlines the study methodology and design, major results, limitations and criticisms, related studies and additional information, and clinical implications. The study presents a set of five diagnostic criteria that approach 100% sensitivity for identifying clinically important cervical spine injuries and could eliminate one-eighth of all cervical spine radiographs ordered for these patients. In addition to outlining the most salient features of the study, a clinical vignette and imaging example are included in order to provide relevant clinical context.
Coronary CT Angiography in Acute Chest Pain
Authors: Lee Christoph I.
Published: September 2016

This chapter, found in the chest pain section of the book, provides a succinct synopsis of a key study examining the use of computed tomography (CT) angiography for triaging patients with acute chest pain. This summary outlines the study methodology and design, major results, limitations and criticisms, related studies and additional information, and clinical implications. The study showed that for patients presenting to the emergency department with symptoms suggesting acute coronary syndromes, incorporating early coronary CT angiography into the triage strategy improves diagnostic efficiency, with more direct discharges from the emergency department and shorter lengths of stay for those admitted. In addition to outlining the most salient features of the study, a clinical vignette and imaging example are included in order to provide relevant clinical context.
Low-Dose CT for Suspected Appendicitis in Young Adults
Authors: Lee Christoph I.
Published: September 2016

This chapter, found in the abdominal and pelvic pain section of the book, provides a succinct synopsis of a key study examining the use of low-dose computed tomography (CT) among young adults with suspected appendicitis. This summary outlines the study methodology and design, major results, limitations and criticisms, related studies and additional information, and clinical implications. Low-dose CT was shown not to be inferior to standard-dose CT with respect to negative appendectomy rates among young adults presenting with suspected appendicitis. If used as the first-line imaging study in a common indication for CT, potential radiation-induced cancer risks can be reduced among this radiosensitive patient population. In addition to outlining the most salient features of the study, a clinical vignette and imaging example are included in order to provide relevant clinical context.
Incidental Meniscal Findings on Knee MRI
Authors: Lee Christoph I.
Published: September 2016

This chapter, found in the bone, joint, and extremity pain section of the book, provides a succinct synopsis of a key study examining the frequency of incidental findings on knee magnetic resonance imaging. This summary outlines the study methodology and design, major results, limitations and criticisms, related studies and additional information, and clinical implications. Incidental meniscal damage on MRI was shown to be common in the general population, especially among the elderly, and is not necessarily attributable to patients’ knee symptoms. Authors advise those interpreting MRI reports and planning interventions that there is a high prevalence of incidental tears even among those without knee symptoms. In addition to outlining the most salient features of the study, a clinical vignette and imaging example are included in order to provide relevant clinical context.
Imaging Utilization Trends and Radiation Exposure
Authors: Lee Christoph I.
Published: September 2016

This chapter, found in the radiation exposure from medical imaging section of the book, provides a succinct synopsis of a key study examining advanced imaging utilization trends and radiation-induced cancer risks. This summary outlines the study methodology and design, major results, limitations and criticisms, related studies and additional information, and clinical implications. Results showed that the utilization rates for advanced imaging in a population enrolled in various integrated health systems increased substantially from 1995 to 2010. Given the potential radiation-induced cancer risks associated with advanced imaging, researchers concluded that the clinical benefits of advanced imaging should be quantified to determine the relative risk-benefit ratios of advanced imaging procedures. In addition to outlining the most salient features of the study, a clinical vignette is included in order to provide relevant clinical context.
Oxford Handbook of Clinical Specialties
Authors: Baldwin Andrew , Hjelde Nina , Goumalatsou Charlotte , Myers Gil
Published: September 2016

This title provides a unique resource for medical students and junior doctors as a definitive guide to the medical specialties. It is divided into 14 chapters, each covering a specialty area, including obstetrics, paediatrics, gynaecology, psychiatry, ophthalmology, primary care, ENT, dermatology, anaesthesia, eponymous syndromes, orthopaedics, trauma, emergency medicine, and pre-hospital care. Each chapter aims to cover the core content of the specialty in a concise and logical way, focussing on presentation, diagnosis and management of specific conditions and giving clear advice on clinical management. A unique feature of both books is the use of humour, anecdotes and philosophical asides, helping ensure a rounded, patient-centred approach to the practise of medicine.
Obstetrics
Authors: Baldwin Andrew , Hjelde Nina , Goumalatsou Charlotte , Myers Gil
Published: September 2016

This chapter explores obstetrics, including obstetric histories, abdominal examination, physiological changes in pregnancy, pre-pregnancy counselling, the placenta, plasma chemistry in pregnancy, antenatal care, structural abnormalities and ultrasound, screening and diagnosis of aneuploidy, minor symptoms of pregnancy, hyperemesis gravidarum, sickle cell disease in pregnancy, cardiac disease in pregnancy, drugs used in psychiatry and epilepsy, anaemia, HIV in pregnancy and labour, diabetes mellitus in pregnancy, thyroid disease in pregnancy, jaundice in pregnancy, malaria, renal disease in pregnancy, epilepsy, respiratory disease in pregnancy, connective tissue diseases in pregnancy, hypertension in pregnancy, thromboprophylaxis, thrombophilia in pregnancy, venous thromboembolism, infection, group B streptococcus (GBS), abdominal pain in pregnancy, sepsis in pregnancy and the puerperium, fetal monitoring in labour, pre-eclampsia, prematurity, small for gestational age (SGA), postmaturity (prolonged pregnancy), maternal collapse, antepartum haemorrhage, prelabour rupture of membranes at term, normal labour, induction of labour, management of delay in labour, home birth, pain relief in labour, multiple pregnancy, breech presentation and other malpresentations/malpositions, cord prolapse, shoulder dystocia, meconium-stained liquor, operative vaginal delivery, caesarean section (CS), uterine rupture, mendelson’s syndrome, stillbirth (intrauterine fetal death, IUD), postpartum haemorrhage (PPH), retained placenta, uterine inversion, placenta praevia, accreta and increta, DIC and coagulation defects, amniotic fluid embolism, birth injuries, episiotomy and tears, the puerperium, maternal and perinatal mortality.
Primary care
Authors: Baldwin Andrew , Hjelde Nina , Goumalatsou Charlotte , Myers Gil
Published: September 2016

This chapter explores primary care and general practice. It outlines primary care (general practice in the UK and worldwide, primary care, intermediate care and self-care, primary health care teams, and pressures of primary care), consulting and certifying (the consultation and patient centred care, consultation models, complex decision making, managing uncertainty, what to do for the best, continuity of care, home visits, telephone consulting, chronic disease, approaching minor illness, medically unexplained symptoms, time off work and fit notes, fitness to drive, fitness to fly, UK benefits, certification of death) health and healthy living (health and social class, social class and health inequalities, prevention, screening, health education, smoking cessation, managing alcohol and drug misuse, managing obesity, managing sleep problems, exercise, healthy eating and alternative medicine, domestic violence), and practice management and performance (GPs as business managers and commissioners, independent practice vs commercial companies, clinical governance, significant events, audit and complaints, appraisal, revalidation and performance, prescribing and referring, patient groups).
Dermatology
Authors: Baldwin Andrew , Hjelde Nina , Goumalatsou Charlotte , Myers Gil
Published: September 2016

This chapter explores dermatology. It includes history and examination, creams and ointments, describing a lesion, patterns of skin disease, itch, skin signs in systemic disease, common skin cancers, malignant melanoma, moles, psoriasis, eczema (dermatitis), skin infections (fungi, bacteria, viruses), acne vulgaris, rosacea, drug eruptions, specific skin disorders (pemphigus and pemphigoid, strawberry naevus, pyogenic granuloma, lichen planus, pityriasis rosea, alopecia, photosensitivity, urticaria), venous ulcers, pressure sores, skin disorders and HIV, infestations, and psychodermatoses.
Orthopaedics
Authors: Baldwin Andrew , Hjelde Nina , Goumalatsou Charlotte , Myers Gil
Published: September 2016

This chapter explores orthopaedics. It outlines terminology in orthopaedics, principles of history and examinations (necks, shoulders, elbows, wrist and hand, back), kyphosis and scoliosis, causes of back pain, management of low back pain, specific and/or sinister pain, examining hips and describing gait, painful hips and limping in children, developmental dysplasia, examining knees, pain in the knee, knees that swell, feet, osteomyelitis, bone tumours, congenital disorders of bone and cartilage, osteochondroses, joint replacement, joint aspiration, joint injections, tendons, and soft tissue and sports injury.
The international and national challenges faced in ensuring prudent use of antibiotics
Authors: Hopkins Susan
Published: September 2016

In April 2014, the World Health Organization reinforced that without urgent coordinated action by most stakeholders the world is headed for a post-antibiotic era in which common infections and minor injuries, which have been treatable for decades, could kill once again. With the rise in the number of infections due to antibiotic-resistant bacteria and the lack of development of new antibiotics, antimicrobial resistance is a major clinical and public health issue that society needs to tackle. This chapter focuses on the challenges of drug resistance and antimicrobial development together with how healthcare organizations can address this threat. A number of initiatives are discussed, including how prescribers and the public need to ensure that antimicrobials are used widely to prevent any collateral damage.
Managing behaviours: social, cultural, and psychological aspects of antibiotic prescribing and use
Authors: Charani Esmita , Birgand Gabriel
Published: September 2016

Antibiotic prescribing in secondary care is suboptimal. The collective term for the myriad of interventions targeting antibiotic prescribing is antimicrobial stewardship. These interventions all aim to help optimize antibiotic prescribing by changing prescribing behaviours. However, there is currently very little evidence from social science incorporated into the design and implementation of these interventions. This is despite emerging evidence suggesting that antibiotic prescribing is influenced by a set of unique cultural and social determinants. In order to better understand how the prescribing process occurs in hospitals and how we can optimize it we need to undertake research into understanding the context in which prescribing decisions are made. Interventions need to be developed which are multidisciplinary in nature and involve active engagement with the teams in which they are implemented. To aid this process we also need to ensure that healthcare professionals proactively receive feedback and education about their prescribing behaviours.
Near-patient testing, infection biomarkers, and rapid diagnostics
Authors: Dryden Matthew
Published: September 2016

Treating patients with targeted antimicrobial therapy is the gold standard of care. However, empiric antimicrobial guidelines are in operation for many patients in primary or secondary care with infection. These guidelines are based on previous surveillance data and/or national recommendations, but the decision to start treatment and the choice of antimicrobial is a best-guess approach, based on clinical judgement. Microbiology laboratory results help guide and target therapies, but in general they take about 1 to 2 days to be available due to the processes involved in culturing organisms. Improvement in speed of diagnosis is the focus of research, particularly around molecular diagnostics. Near-patient testing and the use of biomarkers has been discussed as a way to tackle this issue. This chapter also considers the alternatives and future strategies that could be deployed to improve the targeted therapy of antimicrobials.
Macrovascular complications, hypertension, and lipids
Authors: Levy David
Published: September 2016

Premature vascular disease is common in Type 1 diabetes, especially in women and those with long duration. Many studies have identified early vascular involvement, using carotid Doppler and coronary artery calcification. Symptoms of coronary heart disease are often absent or muted, and the best methods for identifying occult coronary heart disease in Type 1 patients are not known. The concept of ideal cardiovascular health is valuable in planning preventive lifestyle and medical interventions. ‘Essential’ hypertension in young Type 1 patients is common, and reflects increased arterial stiffness. Hypertension is invariable in patients with any degree of albuminuria or renal impairment. Statin treatment in patients over 40 years old is recommended, but the evidence base is weak. Statins and ezetimibe are the only agents of prognostic value currently available for prevention of vascular events. Primary prevention with aspirin needs individual assessment. Insulin resistance/metabolic syndrome is frequent in Type 1 diabetes.
Adolescence and emerging adulthood
Authors: Levy David
Published: September 2016

Adolescence and emerging childhood forms an increasing proportion of the lifespan of urbanized individuals. Glycaemic control worsens during adolescence; physiology and psychology contribute. A1C levels peak around 9% (75 mmol/mol) before declining from late teens onwards. However, unchanging glycaemia (tracking) is common. Glycaemia has generally improved in the past 10–15 years, but significant differences between and within countries persist. Microvascular complications are prevalent at this stage, but have probably also decreased with time. During this important period, the stage can be set for premature macrovascular disease (early onset hypertension, arterial stiffening, dyslipidaemia, and smoking). Exercise reduces the risk of microvascular complications. Smoking is as common in young Type 1 patients than in the general population. Efforts at smoking cessation need reinforcing. Glycaemic control during university does not improve. Transition from paediatric to adult diabetes services is often unsatisfactory; clinics should implement simple procedures focusing on accessibility, flexibility, and improved communications.
Some practical matters
Authors: Levy David
Published: September 2016

Type 1 diabetes in older people can be challenging; food and insulin are taken less reliably, and some have cognitive impairment. Simplify insulin regimens where appropriate; ‘low’ A1C measurements may signify recurrent hypoglycaemia. The regulatory framework for drivers in Europe is less tolerant of serious hypoglycaemia. Intensive education is required and precautions while driving need reinforcing. Severe hypoglycaemia in the young is associated with impaired school performance, especially in verbal IQ and spelling. Educational attainment is not affected by Type 1 diabetes, but there is some evidence for poor progression in employment, especially in women. Though popular, the evidence supporting structured education in Type 1 diabetes is weak. Peer support using social media is increasing; evidence for benefit is lacking. Serious bacterial infections are probably more common. Ensure all Type 1 patients are up to date with immunizations. Periodontal infections, common and sometimes severe, are reciprocally related to glycaemic control.
Patient experiences and perceptions of coercion: universal meaning, individual experiences?
Authors: Canvin Krysia
Published: September 2016

This chapter presents a synthesis of major research themes and findings on patients’ subjective experiences and perceptions of coercion in community psychiatry. Covering the 20-year period from 1994 to 2014, it reviews studies of both formal (legislative) and informal (non-legislative) coercion, including patients’ experiences of mandated community treatment or community treatment orders (CTOs), assertive community treatment (ACT), and leverage. It begins by presenting four concepts that characterize patients’ perceptions: interventions, obligations, threats, and safety. It then reviews the contradictory evidence surrounding patients’ experiences of coercion, including patient comparisons of hospital and community coercion and the implications of coercion for self-determination, ‘normality’, care and services, and for wellness. It concludes by identifying gaps in the literature and recommending future research.
Family carers and coercion in the community
Authors: Rugkåsa Jorun
Published: September 2016

Family members have always been involved in the care of those with mental illness in most parts of the world. This chapter examines the role of family caregivers in coercive practices in the community and shows that family members may exert influence directly or when engaged in the formal or informal coercive practices of professionals, but may also experience themselves as being coerced. Emphasis is placed on carers’ own experiences. Three dimensions of relevance to coercive practices are outlined. First, carers’ interactions with the family member who is unwell; second, their involvement in community treatment; and third, the role attributed to carers in welfare states.
Compulsory community mental health care: Oceania
Authors: O’Brien Anthony J.
Published: September 2016

Oceania is characterized by the diversity of countries and by highly variable provision of mental health services and community mental health care. Countries such as Australian and New Zealand have well-developed mental health services with a high level of provision, but many less developed countries lack mental health infrastructure. Some developing countries such as Samoa and Tonga have passed mental health legislation with provision for community treatment orders, but this legal measure is probably not a useful mechanism for advancing mental health care in developing countries. Instead, efforts to improve provision of care seem best directed to the primary care sector, and to the general health workforce, rather than to specialists. The UN CRPD offer extensions of human rights to people with mental illness and most countries in Oceania have signed it. However, the absence of a regional rights tribunal potentially limits the realization of those rights.
Children Are Special
Authors: Fleischman Alan R.
Published: September 2016

This chapter introduces the reader to the field of pediatric ethics., a unique and important aspect of the discipline of bioethics, the study of moral conduct in healthcare and the rational process for determining the best course of action in the face of conflicting choices. It explains the main principles utilized in bioethics analysis and describes how these principles may be used in pediatric ethics. This chapter also explores what it means to be a child in America and the unique kinship relationships and obligations engendered by the decision of parents to have a child, and it examines professional obligations related to the care of children.
Ethical Issues in Neonatal Intensive Care
Authors: Fleischman Alan R.
Published: September 2016

This chapter begins with a brief history of how healthcare decisions have been made for critically ill newborns since the 1960s. Through case examples, it describes the ethical concerns and examines analytic approaches that help clinicians and parents make hard choices for their critically ill and dying newborns. The principle of “best interests” is examined and its utility and limitations described. The use of infant bioethics committees and consultants is described with examples of how they work. The chapter also covers the important role of government neonatal decision making including the President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research, the Child Abuse Prevention and Treatment Act Amendments of 1984, and the Baby Doe Rules.
Ethical Issues at the End of Life
Authors: Fleischman Alan R.
Published: September 2016

This chapter deals with the difficult ethical issues associated with children who are dying. A recurring theme in the chapter is the role that children can play in planning their own care. The concept of brain death is examined and it is contrasted with cardiac death. The practice of organ donation after cardiac death is described and its ethical justification is questioned. . Several other controversial ethical issues are analyzed, including the distinction between withholding and withdrawing of treatment, withdrawing medically provided hydration and nutrition from infants who are not in the process of dying, whether pain management at the end of life hastens death and is therefore not permitted, and whether children should die in the hospital or at home. The chapter concludes with a description of how to support families after the death of a child.
Introduction
Authors: Sullivan Maria A. , Levin Frances R.
Published: September 2016

Alcohol and substance-use disorders in late life have been under-studied. Alcohol and prescription drugs are frequently abused by older Americans, yet addictive disorders are often difficult to identify in this population because of screening instruments adapted to younger adults, stigma and shame that limit help-seeking in older adults, and co-occurring medical and psychiatric conditions that mimic or mask both acute effects and withdrawal syndromes associated with alcohol or substance-use disorders. We will review the evidence for the effectiveness of motivational brief interventions in this population, the need to modify certain pharmacotherapies, including standard detoxification regimens, as well as how to develop age-specific treatment services which tailor the content and pace of presentation toward older adults. Older patients can demonstrate equally or more successful outcomes than younger individuals. This text is intended as a practical handbook to enhance clinical skills in identifying and treating addiction in older adults.
Benzodiazepines and Other Sedative-Hypnotics in the Older Adult
Authors: Williams Arthur Robin , Bogunovic Olivera J.
Published: September 2016

Sedative-hypnotic-use disorder is a serious problem in the elderly and is a growing concern in the United States. The American Geriatrics Society’s “Choosing Wisely” initiative cautions against the use of any benzodiazepines or other sedative-hypnotics as initial treatment in older adults, yet benzodiazepines are the most frequently prescribed drugs in the elderly for both insomnia and anxiety. Other classes of medication (e.g., serotoninergic antidepressants) may be substituted for benzodiazepines based on diagnosis. With advancing age, the elderly are more sensitive to the potential side effects of benzodiazepines because of altered pharmacokinetics and pharmacodynamics Increasingly, studies have indicated that older patients disproportionately experience adverse events with benzodiazepines such as falls and cognitive deficits and have difficulty reducing or stopping long-term use without experiencing rebound effects such as anxiety and insomnia. Sedative-hypnotic-use disorders among older adults are increasing in prevalence and warrant heightened clinical attention, thoughtful assessment, and active management.