bluuebunny/crossref_metadata_2025 huggingface dataset:
Curcumin Alters Neural Plasticity and Viability of Intact Hippocampal Circuits and Attenuates Behavioral Despair and COX-2 Expression in Chronically Stressed Rats
Authors: Choi Ga-Young , Kim Hyun-Bum , Hwang Eun-Sang , Lee Seok , Kim Min-Ji , Choi Ji-Young , Lee Sung-Ok , Kim Sang-Seong , Park Ji-Ho
Published: January 2017

Curcumin is a major diarylheptanoid component ofCurcuma longawith traditional usage for anxiety and depression. It has been known for the anti-inflammatory, antistress, and neurotropic effects. Here we examined curcumin effect in neural plasticity and cell viability. 60-channel multielectrode array was applied on organotypic hippocampal slice cultures (OHSCs) to monitor the effect of 10 μM curcumin in long-term depression (LTD) through low-frequency stimulation (LFS) to the Schaffer collaterals and commissural pathways. Cell viability was assayed by propidium iodide uptake test in OHSCs. In addition, the influence of oral curcumin administration on rat behavior was assessed with the forced swim test (FST). Finally, protein expression levels of brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2) were measured by Western blot in chronically stressed rats. Our results demonstrated that 10 μM curcumin attenuated LTD and reduced cell death. It also recovered the behavior immobility of FST, rescued the attenuated BDNF expression, and inhibited the enhancement of COX-2 expression in stressed animals. These findings indicate that curcumin can enhance postsynaptic electrical reactivity and cell viability in intact neural circuits with antidepressant-like effects, possibly through the upregulation of BDNF and reduction of inflammatory factors in the brain.
The Development of a Measurement Tool Evaluating Knowledge Related to Sensory Processing among Graduate Occupational Therapy Students: A Process Description
Authors: Gee Bryan M. , Thompson Kelly , Strickland Jane , Miller Lucy Jane
Published: January 2017

With an increased demand arising from stake holders to provide more complex clinical experiences and to have students better prepared for clinical rotations, educators need to develop instructional tasks and measures to teach and assess clinical reasoning. The purpose of this article is to highlight a clinical simulation measure revolving around the A SECRET reasoning approach, which is also generalizable to other conditions and interventions. Preliminary findings of 1st year Master of Occupational Therapy students (n=8) who took part in a pilot of the A SECRET case scenario reported positive, yet not strong, attitudes toward the A SECRET assessment and the sensory processing related content delivered in an online format as a part of a larger study. Overall the student perceptions and the processes of the measure development suggest an inherent value of using the proposed type of simulated case scenarios in assisting occupational therapy students in their program’s first year with the development of clinical reasoning.
Modified Tang and Pun’s Current Comparator and Its Application to Full Flash and Two-Step Flash Current Mode ADCs
Authors: Bhatia Veepsa , Pandey Neeta
Published: January 2017

A modification to an existing current comparator proposed by Tang and Pun has been presented. The circuit introduces a flipped voltage follower (FVF) which replaces the source follower input stage of the existing current comparator of Tang and Pun. This modification culminates into higher speed especially at lower currents and lower power dissipation. The application of the proposed current comparator has also been put forth by implementing a 3-bit current mode (CM) ADC and a two-step 3-bit CM ADC. The theoretical propositions are verified through spice simulation using 0.18 μm TSMC CMOS technology at a power supply of 1.8 V. Propagation delay, power dissipation, and power delay product (PDP) have been calculated for the proposed current comparator and process parameter variation has been studied. For both the implementations of ADCs, performance parameters, namely, DNL, INL, missing codes, monotonicity, offset, and gain errors, have been evaluated.
A Model to Simulate Multimodality in a Mesoscopic Dynamic Network Loading Framework
Authors: Di Gangi Massimo , Polimeni Antonio
Published: January 2017

A dynamic network loading (DNL) model using a mesoscopic approach is proposed to simulate a multimodal transport network considering en-route change of the transport modes. The classic mesoscopic approach, where packets of users belonging to the same mode move following a path, is modified to take into account multiple modes interacting with each other, simultaneously and on the same multimodal network. In particular, to simulate modal change, functional aspects of multimodal arcs have been developed; those arcs are properly located on the network where modal change occurs and users are packed (or unpacked) in a new modal resource that moves up to destination or to another multimodal arc. A test on a simple network reproducing a real situation is performed in order to show model peculiarities; some indicators, used to describe performances of the considered transport system, are shown.
FDA Approval Summary: Sonidegib for Locally Advanced Basal Cell Carcinoma
Authors: Casey Denise , Demko Suzanne , Shord Stacy , Zhao Hong , Chen Huanyu , He Kun , Putman Alexander , Helms Whitney , Keegan Patricia , Pazdur Richard
Published: January 2017

On July 24, 2015, the FDA approved sonidegib (ODOMZO; Novartis) for the treatment of patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy. The approval was based on data from one randomized, double-blind, noncomparative trial of two doses of sonidegib administered to 230 hedgehog inhibitor–naïve patients with metastatic basal cell carcinoma (mBCC, n = 36) or laBCC (n = 194). Patients were randomized 2:1 to receive sonidegib 800 mg (n = 151) or 200 mg (n = 79) daily. The objective response rate (ORR) for patients with laBCC was 58% [95% confidence interval (CI), 45–70] in the 200 mg group and 44% (95% CI, 35–53) in the 800 mg group. The median duration of response for patients with laBCC was nonestimable (NE) in the 200 mg arm and 15.7 months (95% CI, NE) in the 800 mg arm. The ORR for patients with mBCC was 8% (95% CI, 0.2–36) and 17% (95% CI, 5–39) in patients treated with 200 and 800 mg, respectively. The most common adverse events occurring in ≥10% of patients were muscle spasms, alopecia, dysgeusia, nausea, fatigue, increased serum creatine kinase, decreased weight, and diarrhea. Clin Cancer Res; 23(10); 2377–81. ©2017 AACR.
Activation of EIF4E by Aurora Kinase A Depicts a Novel Druggable Axis in Everolimus-Resistant Cancer Cells
Authors: Katsha Ahmed , Wang Lihong , Arras Janet , Omar Omar M. , Ecsedy Jeffrey , Belkhiri Abbes , El-Rifai Wael
Published: January 2017

Purpose: Aurora kinase A (AURKA) is overexpressed in several cancer types, making it an attractive druggable target in clinical trials. In this study, we investigated the role of AURKA in regulating EIF4E, cap-dependent translation, and resistance to mTOR inhibitor, RAD001 (everolimus).

Experimental Design: Tumor xenografts and in vitro cell models of upper gastrointestinal adenocarcinomas (UGC) were used to determine the role of AURKA in the activation of EIF4E and cap-dependent translation. Overexpression, knockdown, and pharmacologic inhibition of AURKA were used in vitro and in vivo.

Results: Using in vitro cell models, we found that high protein levels of AURKA mediate phosphorylation of EIF4E and upregulation of c-MYC. Notably, we detected overexpression of endogenous AURKA in everolimus-resistant UGC cell models. AURKA mediated phosphorylation of EIF4E, activation of cap-dependent translation, and an increase in c-MYC protein levels. Targeting AURKA using genetic knockdown or a small-molecule inhibitor, alisertib, reversed these molecular events, leading to a decrease in cancer cell survival in acquired and intrinsic resistant cell models. Mechanistic studies demonstrated that AURKA binds to and inactivates protein phosphatase 2A, a negative regulator of EIF4E, leading to phosphorylation and activation of EIF4E in an AKT-, ERK1/2-, and mTOR-independent manner. Data from tumor xenograft mouse models confirmed that everolimus-resistant cancer cells are sensitive to alisertib.

Conclusions: Our results indicate that AURKA plays an important role in the activation of EIF4E and cap-dependent translation. Targeting the AURKA–EIF4E–c-MYC axis using alisertib is a novel therapeutic strategy that can be applicable for everolimus-resistant tumors and/or subgroups of cancers that show overexpression of AURKA and activation of EIF4E and c-MYC. Clin Cancer Res; 23(14); 3756–68. ©2017 AACR.
Metabolic Profiling in Formalin-Fixed and Paraffin-Embedded Prostate Cancer Tissues
Authors: Cacciatore Stefano , Zadra Giorgia , Bango Clyde , Penney Kathryn L. , Tyekucheva Svitlana , Yanes Oscar , Loda Massimo
Published: January 2017

Metabolite profiling has significantly contributed to a deeper understanding of the biochemical metabolic networks and pathways in cancer cells. Metabolomics-based biomarker discovery would greatly benefit from the ability to interrogate retrospective annotated clinical specimens archived as formalin-fixed, paraffin-embedded (FFPE) material. Mass spectrometry–based metabolomic analysis was performed in matched frozen and FFPE human prostate cancers as well as isogenic prostate cancer cell lines. A total of 352 and 460 metabolites were profiled in human tissues and cell lines, respectively. Classes and physical–chemical characteristics of the metabolites preserved in FFPE material were characterized and related to their preservation or loss following fixation and embedding. Metabolite classes were differentially preserved in archival FFPE tissues, regardless of the age of the block, compared with matched frozen specimen, ranging from maximal preservation of fatty acids (78%) to loss of the majority of peptides and steroids. Generally, FFPE samples showed a decrease of metabolites with functional groups, such as carboxamide. As an adjunct technique, metabolic profiles were also obtained in situ from FFPE tissue sections where metabolites were extracted in a manner that preserves tissue architecture. Despite the fact that selected metabolites were not retained after processing, global metabolic profiles obtained from FFPE can be used to predict biologic states and study biologic pathways. These results pave the way for metabolomics-based biomarker discovery/validation utilizing retrospective and clinically annotated FFPE collections.

Implications: Metabolic profiles can be performed in archival tissue and may be used to complement other profiling methods such as gene expression for biomarker discovery or pathway analysis in the assessment of biologic states. Mol Cancer Res; 15(4); 439–47. ©2017 AACR.
Prognostic Value of the Pretreatment Advanced Lung Cancer Inflammation Index (ALI) in Diffuse Large B Cell Lymphoma Patients Treated with R-CHOP Chemotherapy
Authors: Park Young Hoon , Yi Hyeon Gyu , Lee Moon Hee , Kim Chul Soo , Lim Joo Han
Published: January 2017

Background: The Advanced Lung Cancer Inflammation Index (ALI, body mass index × albumin/neutrophil-to-lymphocyte ratio) has been demonstrated to be a prognostic factor of survival in some solid cancers. We retrospectively investigated the usefulness of the ALI to predict chemotherapy response and survival in 212 patients with diffuse large B cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. Methods: Patients were allocated to a low ALI group (n = 82, 38.7%) or a high ALI group (n = 130, 61.3%) according to an optimal pretreatment ALI cut-off value of 15.5 as determined by receiver operating curve analysis. Results: The low ALI group displayed more adverse clinical characteristics, lower rates of complete remission (54.9 vs. 75.4%, p = 0.008), and poorer 5-year progression-free (PFS, 58.1 vs. 77.3%, p = 0.006) and overall (OS, 64.2 vs. 80.2%, p = 0.008) survival. Multivariate analysis showed that low ALI was found to independently predict shorter PFS and OS. Interestingly, a low ALI reverted to a high ALI during treatment in 58 patients (27.4%), and the 5-year OS of these patients was better than that of patients whose ALI remained low (n = 24, 72.5 vs. 24%, p < 0.001). Conclusions: ALI might be an easily available marker for predicting clinical outcomes in DLBCL patients treated with R-CHOP chemotherapy.
Open-Angle Glaucoma: Drug Development Pipeline during the Last 20 Years (1995-2015)
Authors: Vicente André , Prud'homme Sylvie , Ferreira Joana , Abegão Pinto Luís , Stalmans Ingeborg
Published: January 2017

Objectives: To analyse drug development for open-angle glaucoma during the last 20 years. Methods: Research was performed by referring to clinical trials registered at the International Clinical Trials Registry Platform (ICTRP). A search for the condition “open-angle glaucoma” with the intervention “drug” was performed. We included trials registered from 01/01/1995 to 01/01/2015, only involving studies in phases 1, 2, and 3. Only studies resorting to novel treatment strategies (either novel drugs or yet-untested fixed associations of approved medication) were considered. Results: We recorded 158 studies for the condition of open-angle glaucoma with a drug-based intervention; 65 of the studies reported phase 2 trials and 74 reported phase 3 trials. Pharmaceutical companies were the primary sponsors of 95.3% of the trials. Most of the studies (66.5%, n = 105) involved a new drug, and the remainder (33.5%, n = 53) tested fixed drug associations. The bulk of the trials (n = 99, 62.7%) involved the use of prostaglandin analogues, either as a comparator or a study drug. In descending order of frequency, the studies conducted involved Rho-kinase inhibitors (n = 15), carbonic anhydrase inhibitors (n = 14), β-blockers (n = 7), angiostatic steroids (n = 6), α2-adrenergic agonists (n = 4), 5-HT2A receptor agonists (n = 4), and NMDA receptor antagonists (n = 2). A cyclin-dependent kinase inhibitor, an LIM-domain kinase 2 inhibitor, an A1 adenosine receptor agonist, catechin, macrolide, saffron, and seawater were each tested in 1 clinical trial. Conclusion: Research into the medical treatment of glaucoma indicates the use of prostaglandin analogues. However, there are a significant number of trials testing other drug classes, particularly Rho-kinase inhibitors. This new focus could lead to a potential increase in the number of therapeutical options for the management of glaucoma in the future.
Implantation of the Subcutaneous Implantable Cardioverter-Defibrillator
Authors: Brouwer Tom F. , Miller Marc A. , Quast Anne-Floor B.E. , Palaniswamy Chandrasekar , Dukkipati Srinivas R. , Reddy Vivek , Wilde Arthur A. , Willner Jonathan M. , Knops Reinoud E.
Published: January 2017

Background—

Alternative techniques to the traditional 3-incision subcutaneous implantation of the subcutaneous implantable cardioverter-defibrillator may offer procedural and cosmetic advantages. We evaluate 4 different implant techniques of the subcutaneous implantable cardioverter-defibrillator.

Methods and Results—

Patients implanted with subcutaneous implantable cardioverter-defibrillators from 2 hospitals between 2009 and 2016 were included. Four implantation techniques were used depending on physician preference and patient characteristics. The 2- and 3-incision techniques both place the pulse generator subcutaneously, but the 2-incision technique omits the superior parasternal incision for lead positioning. Submuscular implantation places the pulse generator underneath the serratus anterior muscle and subfascial implantation underneath the fascial layer on the anterior side of the serratus anterior muscle. Reported outcomes include perioperative parameters, defibrillation testing, and clinical follow-up. A total of 246 patients were included with a median age of 47 years and 37% female. Fifty-four patients were implanted with the 3-incision technique, 118 with the 2-incision technique, 38 with submuscular, and 37 with subfascial. Defibrillation test efficacy and shock lead impedance during testing did not differ among the groups; respectively,
P
=0.46 and
P
=0.18. The 2-incision technique resulted in the shortest procedure duration and time-to-hospital discharge compared with the other techniques (
P
<0.001). A total of 18 complications occurred, but there were no significant differences between the groups (
P
=0.21). All infections occurred in subcutaneous implants (3-incision, n=3; 2-incision, n=4). In the 2-incision group, there were no lead displacements.

Conclusions—

The presented implantation techniques are feasible alternatives to the standard 3-incision subcutaneous implantation, and the 2-incision technique resulted in shortest procedure duration.
Functional Tricuspid Regurgitation Caused by Chronic Atrial Fibrillation
Authors: Utsunomiya Hiroto , Itabashi Yuji , Mihara Hirotsugu , Berdejo Javier , Kobayashi Sayuki , Siegel Robert J. , Shiota Takahiro
Published: January 2017

Background—

Functional tricuspid regurgitation (TR) with a structurally normal tricuspid valve (TV) may occur secondary to chronic atrial fibrillation (AF). However, the clinical and echocardiographic differences according to functional TR subtypes are unclear. Therefore, characterization of functional TR because of chronic AF (AF-TR) remains undetermined.

Methods and Results—

To investigate the prevalence of AF-TR, 437 patients with moderate to severe TR underwent 3-dimensional (3D) transesophageal echocardiography. TR severity was determined by the averaged vena contracta width on apical and parasternal inflow views. The prevalence of AF-TR was 9.2%, whereas that of functional TR because of left-sided heart disease was 45.3%. Clinical features of AF-TR included advanced age, female sex, greater right atrial than left atrial enlargement and lower systolic pulmonary artery pressure compared with left-sided heart disease-TR with sinus rhythm (all
P
<0.05). In 3D TV assessment, patients with AF-TR had a larger TV annular area with weaker annular contraction (both
P
<0.001) but a smaller tethering angle (
P
<0.001) despite a similar leaflet coaptation status compared with patients with left-sided heart disease-TR with sinus rhythm. On multivariable analysis, only the TV annular area in midsystole (coefficient, 0.059; 95% confidence interval, 0.041–0.078 per 100 mm
2
;
P
<0.001) was associated with TR severity in AF-TR. The annular area was more closely correlated with the right atrial volume than right ventricular end-systolic volume in AF-TR (
P
<0.001).

Conclusions—

AF-TR is not rare and is associated with advanced age and right atrial enlargement. TV deformations and their association with right heart remodeling differ between AF-TR and left-sided heart disease-TR. Our results suggest that in patients with TR secondary to AF, TV annuloplasty should be effective because this entity has annular dilatation without leaflet deformation.
Afrotropical Limnophora Robineau-Desvoidy (Diptera, Muscidae) with the description of four new species
Authors: COURI MÁRCIA , PONT ADRIAN
Published: January 2017

All the Afrotopical Limnophora Robineau-Desvoidy (Diptera, Muscidae) deposited in the Natural History Museum, London (United Kingdom) were analyzed, including the types of the species described by Emden, mainly from the British Museum (Natural History) Ruwenzori Expedition of 1934–1935. Diagnoses and notes on all the species recorded from the Afrotropical region are given, together with illustrations of the male terminalia (when sufficient material was available), some of which are given for the first time. We made the following taxonomic changes: Limnophora terrestris Paterson, 1955 is a junior synonym of Limnophora translucida Stein, 1913 (syn. nov.); Limnophora aculeipes latilamellata Malloch, 1921 has its status revised and is elevated to species rank (stat. rev.) with Limnophora aculeipes eurymetopa Emden, 1951 proposed as a junior synonym (syn. nov.); L. majuscula kinangopana Emden, 1951 is also raised to species rank (stat. nov.). Four new species are described: Limnophora alta sp. nov.; Limnophora nuda sp. nov.; Limnophora numerosa sp. nov. and Limnophora sinuosa sp. nov., with illustrations of male terminalia.
How Persistent Are North Atlantic–European Sector Weather Regimes?
Authors: Fereday David
Published: January 2017

Persistent weather regimes in daily North Atlantic–European winter mean sea level pressure (MSLP) fields from the 140-yr Twentieth Century Reanalysis are investigated. The phase space is divided into discrete cells based on quantiles of empirical orthogonal function (EOF) principal components; the cells are thus approximately equally populated. An estimate of persistence is provided in terms of the number of different cells visited for a given trajectory duration. This technique is also applied to the well-known Lorenz63 system, which clearly exhibits two regimes, and the more complex Lorenz96 system where the regime structure is less pronounced. While the analysis identifies the two regimes of both the Lorenz63 and Lorenz96 systems, evidence for comparable regimes in the MSLP data is weaker. Recurrent weather regimes produced by k-means clustering might be expected to be clearly linked to slower-moving regions of phase space, but this is shown not to be the case. Only the region of phase space associated with the negative phase of the North Atlantic Oscillation (NAO) shows any regime-like behavior. Nevertheless, the analysis does reveal some structure to the time evolution of the atmospheric circulation—transitions between neighboring pairs of cells show a preferred direction of evolution in many cases.
Multiyear Droughts and Pluvials over the Upper Colorado River Basin and Associated Circulations
Authors: Abatan Abayomi A. , Gutowski William J. , Ammann Caspar M. , Kaatz Laurna , Brown Barbara G. , Buja Lawrence , Bullock Randy , Fowler Tressa , Gilleland Eric , Gotway John Halley
Published: January 2017

This study analyzes spatial and temporal characteristics of multiyear droughts and pluvials over the southwestern United States with a focus on the upper Colorado River basin. The study uses two multiscalar moisture indices: standardized precipitation evapotranspiration index (SPEI) and standardized precipitation index (SPI) on a 36-month scale (SPEI36 and SPI36, respectively). The indices are calculated from monthly average precipitation and maximum and minimum temperatures from the Parameter-Elevation Regressions on Independent Slopes Model dataset for the period 1950–2012. The study examines the relationship between individual climate variables as well as large-scale atmospheric circulation features found in reanalysis output during drought and pluvial periods. The results indicate that SPEI36 and SPI36 show similar temporal and spatial patterns, but that the inclusion of temperatures in SPEI36 leads to more extreme magnitudes in SPEI36 than in SPI36. Analysis of large-scale atmospheric fields indicates an interplay between different fields that yields extremes over the study region. Widespread drought (pluvial) events are associated with enhanced positive (negative) 500-hPa geopotential height anomaly linked to subsidence (ascent) and negative (positive) moisture convergence and precipitable water anomalies. Considering the broader context of the conditions responsible for the occurrence of prolonged hydrologic anomalies provides water resource managers and other decision-makers with valuable understanding of these events. This perspective also offers evaluation opportunities for climate models.
MRMS QPE Performance East of the Rockies during the 2014 Warm Season
Authors: Cocks Stephen B. , Zhang Jian , Martinaitis Steven M. , Qi Youcun , Kaney Brian , Howard Kenneth
Published: January 2017

Multi-Radar Multi-Sensor (MRMS) quantitative precipitation estimation (QPE) radar only (Q3RAD), Q3RAD local gauge corrected (Q3gc), dual polarization (Dual Pol), legacy Precipitation Processing System (PPS), and National Centers for Environmental Prediction (NCEP) stage IV product performance were evaluated for data collected east of the Rockies during the 2014 warm season. For over 22 000 radar QPE–gauge data pairs, Q3RAD had a higher correlation coefficient (0.85) and a lower mean absolute error (9.4 mm) than the Dual Pol (0.83 and 10.5 mm, respectively) and PPS (0.79 and 10.8 mm, respectively). Q3RAD performed best when the radar beam sampled precipitation within or above the melting layer because of its use of a reflectivity mosaic corrected for brightband contamination. Both NCEP stage IV and Q3gc showed improvement over the radar-only QPEs; while stage IV exhibited the lower errors, the performance of Q3gc was remarkable considering the estimates were automatically generated in near–real time. Regional analysis indicated Q3RAD outperformed Dual Pol and PPS over the southern plains, Southeast/mid-Atlantic, and Northeast. Over the northern United States, Q3RAD had a higher wet bias below the melting layer than both Dual Pol and PPS; within and above the melting layer, Q3RAD exhibited the lowest errors. The Q3RAD wet bias was likely due to MRMS’s overestimation of tropical rain areas in continental regions and applying a high yield reflectivity–rain-rate relationship. An adjustment based on precipitation climatology reduced the wet bias errors by ~22% and will be implemented in the operational MRMS in the fall of 2016.
Audiologic Results following Reimplantation of Cochlear Implants
Authors: Gantz Bruce J. , Lowder Mary W. , McCabe Brian F.
Published: January 2017

Five patients using cochlear implants experienced internal device failure 6 weeks to 4 years following implantation. All devices were removed and new electrodes inserted. Single-channel implants were replaced with multichannel systems in three patients, while the others received identical multichannel implants. The performance on a uniform battery of audiologic tests was the same or better with the second implant in all patients. Replacement of intracochlear electrodes did not induce clinically apparent degeneration of auditory performance in this series.
Factors that Affect Depth Perception in Stereoscopic Displays
Authors: Patterson Robert , Moe Linda , Hewitt Tiger
Published: January 2017

This study investigated several factors that affect depth perception in stereoscopic displays: half-image separation magnitude, separation direction (crossed vs. uncrossed), viewing distance, stimulus size, and exposure duration. The depth perceived under various combinations of levels of these factors was compared with depth predicted by the geometry of stereopsis. Perceived depth in the crossed-separation direction was frequently close to predictions, such that increases in separation and viewing distance produced appropriate increases in perceived depth. Depth in the uncrossed direction was frequently less than that predicted, especially for small stimuli presented at a long viewing distance, with a large half-image separation, and/or with a brief duration. Thus depth in both crossed and uncrossed directions equaled predictions only for large stimuli exposed for a long duration.
Three Years Experience of Adults Admitted to Hospital in North-East Scotland with E.Coli O157
Authors: Cadwgan A.M. , Laing R.B.S. , Dargie L. , Beadsworth M. , Mackenzie A. R. , Douglas J.G.
Published: January 2017

To describe the epidemiology, clinical features, treatment and outcomes of adults with E. coli O157 infection presenting to Aberdeen Royal Infirmary over a three year period. Methods: A retrospective casenote review.

Results: Thirty-two confirmed cases of E. coli O157 infection were admitted between 1997 and 2000. The median age was 58 years (range 16–93). Ten patients (31%) were from the city of Aberdeen and 22 (69%) from surrounding rural areas. Twenty-seven patients (85%) presented between May and October. The source of infection was unknown or unconfirmed in all cases. Bloody diarrhoea was present in 30 (94%). Leucocytosis was present in 18 (63%) but only four patients (13%) had a fever. Six of the 32 patients (19%) developed Haemolytic-Uraemic Syndrome (HUS) of whom 2 died. Ten patients received antibiotics of whom two developed HUS. Twenty-seven of the 32 (85%) had made a full recovery by time of discharge, three (9%) had impaired renal function and two (6%) died in hospital.

Conclusion: E. coli O157 infection tends to occur sporadically in rural areas in North East Scotland. It is not usually associated with fever. Infection occurs more commonly in the summer and autumn. HUS complicates infection in almost one fifth of patients.
Autoerythrocyte Sensitization Syndrome
Authors: Khan S. A. , Cash J. D.
Published: January 2017

A further case of autoerythrocyte sensitization syndrome is reported and the relevant literature is briefly reviewed. It is suggested that the simple intradermal test with autologous red blood cells be performed in all cases presenting with unexplained painful bruising to avoid many unnecessary and laborious laboratory investigations.
Local Steroid Therapy in Painful Orthopaedic Conditions
Authors: Goldie I.
Published: January 2017

Local corticosteroid therapy is often used in the treatment of a variety of painful orthopaedic conditions such as rheumatoid arthritis, osteoarthritis, peritendinitis, tendinous and ligamentous disorders and bursitis.

Steroids have a direct biological activity of two kinds one pertaining to tissue repair, the other to tissue destruction. All tissue components, vessels, cellular compartment and ground substance are affected by steroids. The most important role of these agents in repair is their anti-inflammatory property. They can however be shown to destroy the fundamental building stones of connective tissue, cartilage and bone. This destructive action appears to be dose-dependent.

Clinical appraisal varies. Both beneficial and deleterious effects have been noted. Local steroid therapy has a part to play in rheumatoid arthritis and in soft tissue disorders, but would appear to be of questionable value in patients with osteoarthritis.
Science is Measurement
Authors: Silverstone T.
Published: January 2017

In the assessment of phobic and obsessional states three approaches have been adopted—self rating scales, observer rating scales and physiological measurements. A comprehensive approach utilising all methods is suggested in the evaluation of new treatment techniques.
Colorectal Carcinoma: Presentation and Management in a General Hospital
Authors: Greig J.D. , Thomson W.O.
Published: January 2017

Over a five year period (1981–1986), 44 consecutive patients who presented with colorectal carcinoma were studied prospectively. Forty one (93%) patients underwent surgery, 11 as an emergency. The operative mortality was 7.3% and the wound infection rate was 12.2%. Of the original 44 patients only 18 (41%) are still alive at the end of the study period. The presentation, treatment and prognosis of patients with colorectal cancer in a general hospital are discussed.
The Collapse of Toilets in Glasgow
Authors: Wyatt J.P. , McNaughton G.W , Tullett W.M.
Published: January 2017

Three cases are presented of porcelain lavatory pans collapsing under body weight, producing wounds which required hospital treatment. Excessive age of the toilets was implicated as a causative factor. As many toilets get older episodes of collapse may become more common, resulting in further injuries.
Public Perceptions of Brain Tumours in Scotland: The Need for Access to Appropriate Information
Authors: Whittle I.R. , Broadbent M. , Boyd A. , Lahiri S. , Robbins A. , Kluttig R. , Henderson L. , McMillan J.
Published: January 2017

The aim of the study was to evaluate knowledge and perceptions of brain tumours in a heterogenous, highly educated group of adults living in Edinburgh. Two hundred and forty four respondents answered a questionnaire about the causes, effects and treatments of brain tumours. There were misconceptions about several clinical and biological aspects of intracranial tumours although most respondents were aware of the bleak prognosis associated with many neoplasms. These results, from the intellectual elite of Scotland's capital, suggest that access to information about brain tumours should be readily available. Five leaflets, covering various aspects of brain tumours, that are available through the recently established Scottish charity Brain Tumour Action seem well formulated to address areas of concern and misconception.
International Law, Telemedicine & Health Insurance: China as a Case Study
Authors: McLean Thomas R.
Published: January 2017

Whosoever commands the trade of the world commands the riches of the world and hence the world itself.

Sir Walter Raleigh
Sex and the Surgeon's Knife: The Family Court's Dilemma … Informed Consent and the Specter of Iatrogenic Harm to Children with Intersex Characteristics
Authors: Gurney Karen
Published: January 2017

“When I use a word,” Humpty Dumpty said, in a rather scornful tone, “it means just what I choose it to mean, neither more nor less.”

”The question is,” said Alice, “whether you can make words mean so many different things.”

”The question is,” said Humpty Dumpty, “which is to be master - that's all.”

—Lewis Carroll

“Sex” is a complex thing. The word conjures up many images according to how it is used. When narrowed to the context of the law, however, a person’s sex can be broken down into three primary categories: biological sex, common law sex, and legal sex.

Biological sex has traditionally been determined according to the presence or absence of genitals and gonads (phenotype), and the configuration of the sex chromosomes (karyotype).
Essay: The Limits of Conscience: Moral Clashes over Deeply Divisive Healthcare Procedures
Authors: Wilson Robin Fretwell
Published: January 2017

Refusals by individual pharmacies and pharmacists to fill prescriptions for emergency contraceptives (“EC”) have dominated news headlines, from the Washington Post to the Miami Herald. In the act that sparked a firestorm of controversy, an Eckerd pharmacist refused to fill a rape victim’s prescription for Plan B. A few months later, 11 Alabama nurses resigned positions at state clinics rather than provide EC against their moral convictions. These refusals do not seem to be driven by moral concerns about promiscuity, since pharmacists have refused to dispense Plan B to married couples as well. Instead, the refusals reflect moral and religious concerns about facilitating an act that would cut-off a potential human life.
Right Idea, Wrong Result—Canada's Access to Medicines Regime
Authors: Goodwin Paige E.
Published: January 2017

In 2007, an estimated 33.2 million people were living with HIV, 2.5 million had become infected, and 2.1 million died from the virus. The majority of infected individuals reside in Africa, where in some countries as many as 33.4% of adults have HIV. In developed countries, effective drug therapies have reduced AIDS-related deaths by over seventy percent each year. These drugs have been so effective that over the last two years the global number of individuals dying from AIDS-related illness has actually declined. These therapies, however, are currently sold for $10,000 USD a year, a purchase price that is not feasible for low income countries where the annual health expenditure may be only $29 per person. A lack of essential medicine is not only a problem for those suffering from AIDS. Low and middle-income countries are disproportionately burdened by many additional chronic and infectious illnesses. The World Health Organization (“WHO”) estimates that one third of the world's population cannot regularly access essential medicines. The WHO cites the high cost of drugs as one of the major hurdles countries face in obtaining access to medication. However, the high cost of these brand-name medications does not reflect their minimal production costs. Drug manufacturers can produce generic versions of these drugs for as little as 1/30th of the cost of their brand-name counterparts.
The Patient Life: Can Consumers Direct Health Care?
Authors: Schneider Carl E. , Hall Mark A.
Published: January 2017

The ultimate aim of health care policy is good care at good prices. Managed care failed to achieve this goal through influencing providers, so health policy has turned to the only market-based option left: treating patients like consumers. Health insurance and tax policy now pressure patients to spend their own money when they select health plans, providers, and treatments. Expecting patients to choose what they need at the price they want, consumerists believe that market competition will constrain costs while optimizing quality. This classic form of consumerism is today's health policy watchword.

This article evaluates consumerism and the regulatory mechanism of which it is essentially an example — legally mandated disclosure of information. We do so by assessing the crucial assumptions about human nature on which consumerism and mandated disclosure depend. Consumerism operates in a variety of contexts in a variety of ways with a variety of aims. To assess so protean a thing, we ask what a patient's life would really be like in a consumerist world The literature abounds in theories about how medical consumers should behave. We look for empirical evidence about how real people actually buy health plans, choose providers, and select treatments.

We conclude that consumerism, and thus mandated disclosure generally, are unlikely to accomplish the goals imagined for them. Consumerism's prerequisites are too many and too demanding. First, consumers must have choices that include the coverage, care-takers, and care they want. Second, reliable information about those choices must be available. Third, information must be put before consumers, especially by doctors. Fourth, consumers must receive the information. Fifth, the information must be complete and comprehensible enough for consumers to use it. Sixth, consumers must understand what they are told. Seventh, consumers must be willing to analyze the information. Eighth, consumers must actually analyze the information and do so well enough to make good choices.

Our review of the empirical evidence concludes that these prerequisites cannot be met reliably most of the time. At every stage people encounter daunting hurdles. Like so many other dreams of controlling costs and giving patients control, consumerism is doomed to disappoint. This does not mean that consumerist tools should never be used. It means they should not be used unadvisedly or lightly, but discreetly, advisedly, soberly, and in the fear of error.
Searching for Safety: Addressing Search Engine, Website, and Provider Accountability for Illicit Online Drug Sales
Authors: Liang Bryan A. , MacKey Tim
Published: January 2017

Online sales of pharmaceuticals are a rapidly growing phenomenon. Yet despite the dangers of purchasing drugs over the Internet, sales continue to escalate. These dangers include patient harm from fake or tainted drugs, lack of clinical oversight, and financial loss. Patients, and in particular vulnerable groups such as seniors and minorities, purchase drugs online either naïvely or because they lack the ability to access medications from other sources due to price considerations. Unfortunately, high risk online drug sources dominate the Internet, and virtually no accountability exists to ensure safety of purchased products. Importantly, search engines such as Google, Yahoo, and MSN, although purportedly requiring “verification” of Internet drug sellers using PharmacyChecker.com requirements, actually allow and profit from illicit drug sales from unverified websites. These search engines are not held accountable for facilitating clearly illegal activities. Both website drug seller anonymity and unethical physicians approving or writing prescriptions without seeing the patient contribute to rampant illegal online drug sales. Efforts in this country and around the world to stem the tide of these sales have had extremely limited effectiveness. Unfortunately, current congressional proposals are fractionated and do not address the key issues of demand by vulnerable patient populations, search engine accountability, and the ease with which financial transactions can be consummated to promote illegal online sales. To deal with the social scourge of illicit online drug sales, this article proposes a comprehensive statutory solution that creates a no-cost/low-cost national Drug Access Program to break the chain of demand from vulnerable patient populations and illicit online sellers, makes all Internet drug sales illegal unless the Internet pharmacy is licensed through a national Internet pharmacy licensing program, prohibits financial transactions for illegal online drug sales, and establishes criminal penalties for all parties—including websites, search engines, and health care providers—who engage in and facilitate this harmful activity.
Hastening Death: Dying, Dignity and the Organ Shortage Gap
Authors: Baginski Wojciech
Published: January 2017

Imagine that you are lying in a hospital: conscious, partially paralyzed, and terminally ill. Physicians predict that you will die in a couple of weeks. You have heard about the shortage of viable organs in the United States and consider consenting to transplantation of your organs after you die. Trying not to think about your imminent death, you open the New York Times brought by your family and skim the table of contents. You notice an article and slowly start to read. The headline reads “Surgeon Accused of Hurrying Death of Patient to Get Organs.” After you finish reading, you are not willing to donate your organs for transplantation. It does not matter that you are altruistic or that you want your life-sustaining treatment to be removed when your condition worsens. You do not want your death to be hastened. You do not want the physician to play God. You want to die with dignity in a peaceful and friendly environment.
From Concierge Medicine to Patient-Centered Medical Homes: International Lessons & the Search for a Better Way to Deliver Primary Health Care in the U.S.
Authors: Majette Gwendolyn Roberts
Published: January 2017

Primary care is crucial to the United States health care system. It is essential to the provision of high quality care; including the ability to reach health outcomes, ensure patient satisfaction, and facilitate efficient resource use. Primary care also places strong “emphasis on health promotion, disease prevention, and care of the chronically ill.”

Physicians have introduced two business models in their attempts to improve the delivery of primary care: Concierge Medicine (“CM”) and the Patient Centered Medical Home (“PCMH”). Both models provide personalized, comprehensive preventive care services.

CM is a private medical practice in which the physician charges patients an annual fee to be a patient in the practice. In exchange, the physician limits the number of patients in order to offer more personalized services and amenities such as: direct access through email or cell phone, same day or next day appointments, longer, more personalized appointments, house calls, and physician accompaniment to a specialist.
Autism in the U.S.: Social Movement and Legal Change
Authors: Caruso Daniela
Published: January 2017

The social movement surrounding autism in the U.S. has been rightly defined a ray of light in the history of social progress. The movement is inspired by a true understanding of neuro-diversity and is capable of bringing about desirable change in political discourse. At several points along the way, however, the legal reforms prompted by the autism movement have been grafted onto preexisting patterns of inequality in the allocation of welfare, education, and medical services. In a context most recently complicated by economic recession, autism-driven change bears the mark of political and legal fragmentation. Distributively, it yields ambivalent results that have not yet received systemic attention. This article aims to fill this analytical vacuum by offering, first, a synoptic view of the several legal transformations brought about or advocated for by the autism movement and, second, a framework for investigating their distributive consequences.
You Can't Say That on Television: Constitutional Analysis of a Direct-to-Consumer Pharmaceutical Advertising Ban
Authors: Mulligan Lia
Published: January 2017

In one year, you will watch roughly sixteen hours of pharmaceutical advertisements. Sometime during those sixteen hours, you may recognize in yourself the symptoms portrayed in the advertisements. You may even wonder whether you would benefit from a particular drug. But will you visit your doctor with the fear that you may be suffering from a previously undiagnosed disease? Will you encourage your doctor to prescribe the medication you saw in the advertisements? Will your insurance cover the costs of your medication? More importantly, will you even need the medication at all?

The trend in the pharmaceutical industry to increase yearly spending on direct-to-consumer pharmaceutical advertising (DTCA) seems almost disrespectful considering the magnitude of the healthcare crisis in which the United States is currently embroiled. This notion is inflamed when accounting for the fact that (arguably) one of the biggest problems in our healthcare system is the amount of money spent on healthcare each year.
Confronting the Vector of Tobacco-Related Disease
Authors: Allen Matthew
Published: January 2017

It has been estimated that the use of tobacco kills nearly 6 million people each year, with most deaths occurring in low- and middle-income countries. This disparity is expected to increase over the next few decades. On the basis of current trends, tobacco use will kill more than 8 million people worldwide per annum by 2030, with eighty percent of those premature deaths occurring in low- and middle-income countries. The significant burden of morbidity and mortality associated with tobacco use is well documented and proven and will not be repeated here.

The evidence base for addressing the tobacco epidemic domestically, regionally, and globally has developed in a systematic fashion over the past five decades. Effective measures for tobacco control are now well known and have been canvassed widely in the published literature.
Jimmo and the Improvement Standard: Implementing Medicare Coverage Through Regulations, Policy Manuals and other Guidance
Authors: Gladieux Jennifer E. , Basile Michael
Published: January 2017

In Jimmo v. Sebelius, the plaintiffs alleged that the Centers for Medicare and Medicaid Services (CMS) regularly and improperly denied Medicare reimbursement for outpatient therapy treatment when the beneficiary did not show a likelihood of improvement. These denials, based on policy manuals and other guidance, appear to contradict the government's own regulations, which specifically prohibit coverage denials based solely on the so-called “Improvement Standard.” In Jimmo, the United States District Court for the District of Vermont found that CMS' use of the Improvement Standard may have violated the rulemaking provisions of the Administrative Procedure Act (APA) and denied CMS' motion for summary judgment. Subsequently, the parties settled out of court.

In the settlement, CMS agreed to revise its policy manuals to clarify that the Improvement Standard was not an acceptable basis on which to deny Medicare coverage. CMS declined to defend its policies even though courts often grant deference to agency interpretations. The settlement implies that the agency feared that it would not have received such deference. It also implies that future Supreme Court decisions may give less deference to agency interpretations.