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Plasma gamma-glutamyltransferase (GGT) was suggested to reflect the level of systemic oxidative stress. Oxidative stress induces changes in arterial structure and function and contributes to the development of hypertension. Therefore, GGT may be associated with arterial remodeling and blood pressure (BP) increment, even in absence of disease. To test this hypothesis, we evaluated, in 825 healthy subjects at low cardiometabolic risk, the associations of plasma GGT with carotid artery intima-media thickness (IMT), luminal diameter and prehypertension; in 154 subjects was evaluated also the association with aortic stiffness (cfPWV). Associations were controlled for insulin sensitivity, C-reactive protein, and life-style habits. In the main population, BP was remeasured after 3 years. Carotid diameter and cfPWV, but not IMT, were directly and independently related to plasma GGT. Subjects with prehypertension (N = 330) had higher GGT as compared with subjects with normal BP (22 [14] vs 17 [11] IU/L; adjusted P = 0.001), and within prehypertensive subjects, those who developed hypertension during 3 years had higher GGT than those without incident hypertension (27 [16] vs 21 [14] IU/L; adjusted P < 0.05). Within subjects with arterial stiffness measurement, those with prehypertension (N = 79) had higher both GGT and arterial stiffness (25 [14] vs 16 [20] IU/L and 9.11 ± 1.24 vs 7.90 ± 0.94 m/s; adjusted P < 0.01 and

This foundational chapter presents Mitchell’s writing as a barometer of the times that he inhabited. It sets out the book’s biographical and critical aims to examine the precise nature of the author’s literary achievement against the dramatic geopolitical background of the early decades of the twentieth century. Drawing authoritatively upon original sources, Mitchell’s short life is summarised as a triumph of innate talent over the social hardship and cultural poverty of his upbringing, from his origins in peasant society to service in the army and the airforce, thereafter moving to city life in Scotland and London, before finally settling in Welwyn Garden City. Mitchell’s personal experience of many of the key developments of the modern world, in country and city, at home and abroad, in wartime and peacetime, is shown to have shaped his personal ideology – particularly his left-wing radicalisation. The two central planks of his greatest writing, his love of nature and his fierce social commitment, are traced to his peasant upbringing as son to a poor Aberdeenshire crofter. His literary corpus is presented as a knowing response to the zeitgeist of the inter-war years, as a renunciation of outmoded Victorian modes and an embracing of the new.

Mitchell’s abiding interest in history and prehistory was a concomitant of his overarching commitment to human rights. This chapter studies the impulse underlying his dedication to the Diffusionist school of history, which most importantly served as a moral prop for his belief in human goodness. The four full-length history books that he published span his writing career and testify to the continuity of his ideological preoccupations, expressly with the welfare of the ordinary people and with the responsibilities of mankind with regard to safeguarding the rights of ethnic peoples and respecting the natural environment. His anti-imperialist sensibility is evident in his promotion of the rights of the peasant. This runs right through his biography of Mungo Park, with whom the author keenly empathises as son to a smallscale Scottish farmer, and his study of the pre-Columbian theocracies in his most academic treatise The Conquest of the Maya right up to his study of Fridtjof Nansen, which closes his final volume Nine Against the Unknown, hailed as the champion and embodiment of the most inspiring ethical, environmental, political and philosophical values.

Mitchell’s early fiction writing is analysed as a modern take on Arabian Fantasy mixing realism and mysticism and forging a strong spirit of place from memories of his army service in the middle east, particularly his principal posting in post-war Cairo. Mitchell’s story-cycles appear stylistically dated, but his experimentation, particularly with first person narrative, anticipates several of the signature features of his mature fiction style. The social and political temper of this early work is also seen to be reflective of his mature humanitarianism, in the subtle denunciation of colonialism and in the socialist utopianism seen at play throughout the narrative.

Mitchell’s first two novels are examined as works deploying the medium of imaginative literature for introspection and analysis of his own past. In reverse chronological order they recreate the narrative of his childhood and early adulthood, in the course of which they present a state of the nation critique of early twentieth century Britain. The forthright verisimilitude of the social realism is in keeping with the philosophical nihilism prevailing in the inter-war years, with the political responses of mainstream parties and of radical splinter groups such as the Anarchocommunist Party appearing unable to change society for the better. Mitchell’s technical experimentation with metafiction and intertextuality indicates the scale of his literary ambition, while his proto-feminist sympathies are marked by his reliance on female protagonists.

A quarter of this monograph is devoted to Gibbon’s masterpiece, the trilogy A Scots Quair, approached as a strategically integrated volume. This chapter places the book within its contemporary context, using original research to focus authoritatively on the aims and ideals that shaped its social, political, cultural and philosophical achievement. Sunset Song garners greatest attention for its bespoke narrative techniques and for the eclectic deployment of literary influences from Scotland and elsewhere. The nostalgic power and moral impact of this first novel as a compelling bildungsroman and an elegy for the crofting society destroyed by the war feeds into the more overtly political character of the remaining parts of the trilogy. The revolutionary political perspective at the heart of the work is convincingly based on the author’s ready identification with the subaltern classes, marking it as the highest form of littérature engagée. The Gibbon contributions to Scottish Scene are considered in relation to the central achievement of the trilogy, with the Scottish stories replicating the author’s signature style and, in ‘Forsaken’, successfully carrying it to a more sophisticated level of stylistic experimentation. The polemical essays are welcomed for shedding light on the author’s ideas and beliefs, about literature, politics, history and religion.

Lewis Grassic Gibbon galvanized the Scottish literary scene in 1932 with Sunset Song, the first novel of the epic trilogy A Scots Quair, that drew vividly upon his deprived upbringing on a small croft in Aberdeenshire to capture the zeitgeist of the early twentieth century. Yet his literary legacy extends significantly beyond his breakout book. The seventeen volumes that he amassed in his short life, under his own name of James Leslie Mitchell as well as his Scots pseudonym, demonstrate his versatility, as historian, essayist, biographer and fiction writer. His corpus pays testimony to his core principles, rooted in his rural upbringing: his restless humanitarianism and his deep veneration for the natural world. Set against an informed conspectus of Mitchell’s life and times and incorporating substantive new source material, this study provides a comprehensive and searching analysis of the canon of a combative writer whose fame in recent years – as cultural nationalist, left-wing libertarian, proto-feminist, neo-romantic visionary and trailblazing modernist – has carried far beyond his native land. In tune with the intellectual climate of the inter-war years, Gibbon emerges as a passionate advocate of revolutionary political activism; in addition, as a profound believer in the overarching primacy of nature, he is represented as a supreme practitioner in the field of ecofiction. Coupled with his modernist experimentation with language and narrative, this firmly establishes him amongst the foremost fiction writers of the twentieth century – uniquely, a figure whose achievement has consistently won both critical and popular acclaim.

Context Many hospitals in the United States are exploring greater investment in community health activities that address upstream causes of poor health. Objective Develop and apply a measure to categorize and estimate the potential impact of hospitals' community health activities on population health and equity. Design, setting, and participants We propose a scale of potential impact on population health and equity, based on the cliff analogy developed by Jones and colleagues. The scale is applied to the 317 activities reported in the community health needs assessment implementation plan reports of 23 health care organizations in the Minneapolis-St Paul, Minnesota, metropolitan area in 2015. Main outcome measure Using a 5-point ordinal scale, we assigned a score of potential impact on population health and equity to each community health activity. Results A majority (50.2%) of health care organizations' community health activities are classified as addressing social determinants of health (level 4 on the 5-point scale), though very few (5.4%) address structural causes of health equity (level 5 on the 5-point scale). Activities that score highest on potential impact fall into the topic categories of "community health and connectedness" and "healthy lifestyles and wellness." Lower-scoring activities focus on sick or at-risk individuals, such as the topic category of "chronic disease prevention, management, and screening." Health care organizations in the Minneapolis-St Paul metropolitan area vary substantially in the potential impact of their aggregated community health activities. Conclusions Hospitals can be significant contributors to investment in upstream community health programs. This article provides a scale that can be used not only by hospitals but by other health care and public health organizations to better align their community health strategies, investments, and partnerships with programming and policies that address the foundational causes of population health and equity within the communities they serve.

Morvan's syndrome is an autoimmune disorder of peripheral and central nervous system mediated by VGKC antibody. Here we report a case of Morvans syndrome who presented 1 month after ayurvedic drug intake. She presented with symptoms of peripheral nerve hyperexcitablity and autoimmune testing revealed positive result for VGKC antibody. Heavy metals level was also significantly raised. She improved after a course of steroids. This case report tries to highlight the association of VGKC mediated Morvans syndrome with heavy metal poisoning and its incidental occurence after Ayurvedic drug intake.

Clinicians face many challenges when diagnosing and treating breast cancer. These challenges include interpreting and co-locating information between different medical imaging modalities that are used to identify tumours and predicting where these tumours move to during different treatment procedures. We have developed a novel automated breast image analysis workflow that integrates state-of-the-art image processing and machine learning techniques, personalized three-dimensional biomechanical modelling and population-based statistical analysis to assist clinicians during breast cancer detection and treatment procedures. This paper summarizes our recent research to address the various technical and implementation challenges associated with creating a fully automated system. The workflow is applied to predict the repositioning of tumours from the prone position, where diagnostic magnetic resonance imaging is performed, to the supine position where treatment procedures are performed. We discuss our recent advances towards addressing challenges in identifying the mechanical properties of the breast and evaluating the accuracy of the biomechanical models. We also describe our progress in implementing a prototype of this workflow in clinical practice. Clinical adoption of these state-of-the-art modelling techniques has significant potential for reducing the number of misdiagnosed breast cancers, while also helping to improve the treatment of patients.

Purposes To assess the impact of a government‐sponsored reimbursement policy for cholinesterase inhibitors (ChEIs) on trends in physician visits with a diagnosis of Alzheimer's disease (AD). Methods Longitudinal population‐based study using interrupted time series methods. British Columbia outpatient claims data for individuals aged 65 and older were used to compute monthly AD visit rates and examine the impact of the ChEI reimbursement policy on the coding of AD. We examined trends in the number of patients with AD visits, the number of AD visits per patient, and visits with “competing” diagnoses (mental, neurological, and cerebrovascular disorders and accidental falls). Finally, we described demographic and clinical features of diagnosed patients. Results We analyzed 1.9 million AD visits. Faster growth in recorded AD visits was observed after the policy was implemented, from monthly growth of 7.5 visits per 100 000 person‐months before the policy (95% confidence interval [CI], 6.1‐8.9) to monthly growth of 16.5 per 100 000 person‐months after the policy (95% CI, 14.8‐18.3). After the implementation of the policy, we observed increased growth in the number of patients with recorded AD visits and the number of AD visits per patient, as well as a shift in diagnoses away from mental diseases and accidental falls to AD (diagnosis substitution). Conclusions British Columbia's reimbursement policy for ChEIs was associated with a significant acceleration in Alzheimer's visits. Evaluations of health services utilization and clinical outcomes following drug policy changes need to consider policy‐induced influences on the reliability of the data used in the analysis.

How to cite this article: Jeyaraj KM. Revisiting Post-stroke Epilepsy. Bengal Physician Journal 2020;7(1):22.

We report about two young males who developed significant proximal weakness of all four limbs secondary to intracranial hypertension due to intracranial venous sinus thrombosis. Intracranial venous sinus thrombosis can manifest in a variety of ways which includes isolated intracranial hypertension, focal neurological symptoms or signs and acute or subacute encephalopathy. Various false localising signs have been reported to occur in patients with raised intracranial pressure including cranial nerve palsies and extensive radiculopathy. In a patient presenting with flaccid areflexic quadriparesis and papilledema, the possibility of a potentially reversible dysfunction of the cranial nerves and spinal nerve roots due to a marked rise in intracranial and intraspinal pressure must be recognised. Lumboperitoneal shunt to reduce the intraspinal pressure on the spinal nerve roots has been advocated to reverse the symptoms of extensive radiculopathy in such patients. Both of our patients showed remarkable improvement in symptoms and signs with medical treatment of CVT.

SUMMARY Objective: The safety and tolerability of three treatments for diabetic peripheral neuropathic pain (DPNP) were compared. Methods: A 12-week, randomized, open-label study confirming the non-inferiority of duloxetine (N = 138) vs. pregabalin (N = 134) and the combination of duloxetine plus gabapentin (N = 135) as the primary outcome was previously published. Patients had an inadequate pain response to a stable dose of gabapentin (≥ 900 mg/day) for ≥ 5 weeks prior to study enrolment. Data from that study were assessed in this current analysis for a detailed report of safety and tolerability. Results: Completion rates did not differ significantly between the groups. Discontinuation because of adverse events was significantly greater in the duloxetine (19.6%) vs. pregabalin group (10.4%; p = 0.04); no differences emerged between the duloxetine vs. duloxetine plus gabapentin (13.3%) groups (p = 0.19) or pregabalin vs. duloxetine plus gabapentin groups (p = 0.57). Adverse event rates varied: nausea, insomnia, hyperhidrosis and decreased appetite were reported significantly more often in patients treated with duloxetine vs. patients treated with pregabalin (each p ≤ 0.01); insomnia significantly more in patients treated with duloxetine vs. duloxetine plus gabapentin (p = 0.01); peripheral oedema significantly more in patients treated with pregabalin vs. duloxetine and duloxetine plus gabapentin (p ≤ 0.001 each) and nausea, hyperhidrosis, decreased appetite and vomiting significantly more in patients treated with duloxetine plus gabapentin vs. pregabalin (each p ≤ 0.05). At end-point, weight change differed significantly among treatment groups: patients in the pregabalin group on average gained weight (1.0 0.04 kg); while, patients in the duloxetine and duloxetine plus gabapentin groups on average lost weight (2.39 0.04 and 1.06 0.04 kg, respectively) (pregabalin vs. duloxetine, p ≤ 0.001; pregabalin vs. duloxetine plus gabapentin, p ≤ 0.001; duloxetine vs. duloxetine plus gabapentin, p = 0.01). Conclusion: Duloxetine, pregabalin and duloxetine plus gabapentin were generally safe and tolerable for the treatment of DPNP. What’s known

We present a workflow for producing a statistical shape model (SSM) of the femur with automatically defined regions resembling general anatomic features. Explicitly defined regions enforce correspondence of anatomical features, and allow the shapes of regions to be analysed independently if needed. A training set of manually segmented femur surfaces are partitioned according to Gaussian curvature. Partitioned regions across the training set are then grouped using mean-shift clustering to identify the most stable regions into which surfaces are divided. Reference piecewise parametric meshes are designed for and fitted to each region, and used to train regional SSMs through fitting–training iterations. Fitted region meshes are assembled into full femur meshes for training a whole femur region-based SSM (rSSM). Partitioning, clustering and shape modelling results are presented for 41 femurs. In comparison to a non-regional SSM, the rSSM was more efficient and correspondent in its approximation of unseen femurs.

SummaryWhat is known and objective Sacubitril/valsartan (LCZ696) has been recently approved for the treatment of heart failure (HF) patients with reduced ejection fraction. Several HF patients receive statins as co-medication. Methods Because clearance of statins is meditated via OATP1B1/1B3, the inhibition potential of these transporters by LCZ696 analytes was evaluated in vitro. Furthermore, an open-label, fixed-sequence clinical study was conducted to determine the effect of LCZ696 on the exposure of simvastatin and its active metabolite simvastatin acid. In this clinical study, 26 healthy subjects received simvastatin 40 mg alone or in combination with LCZ696 or after 1 or 2 h of LCZ696 dosing. Results and discussion Although no significant inhibition by LBQ657 (an active metabolite of sacubitril) and valsartan was observed, sacubitril inhibited OATP1B1 and OATP1B3 in vitro, with IC50 of 1·91 and 3·81 μm, respectively. Upon co-administration of simvastatin with LCZ696, the Cmax of simvastatin and simvastatin acid decreased by 7% and 13%, respectively. When administered 1 h after LCZ696 dosing, the corresponding Cmax of simvastatin and simvastatin acid decreased by 16% and 4%, respectively. When administered 2 h after LCZ696 dosing, the Cmax of simvastatin decreased by 33% and that of simvastatin acid increased by 16%. However, no notable changes were observed in the AUCs of simvastatin or simvastatin acid upon co-administration or time-separated administration with LCZ696. No notable impact of simvastatin co-administration was observed on the pharmacokinetics of LCZ696 analytes. LCZ696 and simvastatin were generally well tolerated when administered alone or in combination. What is new and conclusions Overall, the results of this study suggest that although sacubitril inhibited OATP1B1 and OATP1B3 in vitro, it does not translate into any clinically relevant in vivo effect.

Tumor-suppressor genes (TSGs) have been classically defined as genes whose loss of function in tumor cells contributes to the formation and/or maintenance of the tumor phenotype. TSGs containing nonsense mutations may not be expressed because of nonsense-mediated RNA decay (NMD). We combined inhibition of the NMD process, which clears transcripts that contain nonsense mutations, with the application of high-density single-nucleotide polymorphism arrays analysis to discriminate allelic content in order to identify candidate TSGs in five breast cancer cell lines. We identified ARID1A as a target of NMD in the T47D breast cancer cell line, likely as a consequence of a mutation in exon-9, which introduces a premature stop codon at position Q944. ARID1A encodes a human homolog of yeast SWI1, which is an integral member of the hSWI/SNF complex, an ATP-dependent, chromatin-remodeling, multiple-subunit enzyme. Although we did not find any somatic mutations in 11 breast tumors, which show DNA copy-number loss at the 1p36 locus adjacent to ARID1A, we show that low ARID1A RNA or nuclear protein expression is associated with more aggressive breast cancer phenotypes, such as high tumor grade, in two independent cohorts of over 200 human breast cancer cases each. We also found that low ARID1A nuclear expression becomes more prevalent during the later stages of breast tumor progression. Finally, we found that ARID1A re-expression in the T47D cell line results in significant inhibition of colony formation in soft agar. These results suggest that ARID1A may be a candidate TSG in breast cancer.

OBJECTIVE To determine whether duloxetine is noninferior to (as good as) pregabalin in the treatment of pain associated with diabetic peripheral neuropathy. PATIENTS AND METHODS We performed a 12-week, open-label study of patients with diabetic peripheral neuropathic pain who had been treated with gabapentin (≥900 mg/d) and had an inadequate response (defined as a daily pain score of ≥4 on a numerical rating scale [0-10 points]). The first patient was enrolled on September 28, 2006, and the last patient visit occurred on August 26, 2009. Patients were randomized to duloxetine monotherapy (n=138), pregabalin monotherapy (n=134), or a combination of duloxetine and gabapentin (n=135). The primary objective was a noninferiority comparison between duloxetine and pregabalin on improvement in the weekly mean of the diary-based daily pain score (0- to 10-point scale) at end point. Noninferiority would be declared if the mean improvement for duloxetine was no worse than the mean improvement for pregabalin, within statistical variability, by a margin of –0.8 unit. RESULTS The mean change in the pain rating at end point was –2.6 for duloxetine and –2.1 for pregabalin. The 97.5% lower confidence limit was a –0.05 difference in means, establishing noninferiority. As to adverse effects, nausea, insomnia, hyperhidrosis, and decreased appetite were more frequent with duloxetine than pregabalin; insomnia, more frequent with duloxetine than duloxetine plus gabapentin; peripheral edema, more frequent with pregabalin than with duloxetine; and nausea, hyperhidrosis, decreased appetite, and vomiting, more frequent with duloxetine plus gabapentin than with pregabalin. CONCLUSION Duloxetine was noninferior to pregabalin for the treatment of pain in patients with diabetic peripheral neuropathy who had an inadequate pain response to gabapentin. Trial Registration: clinicaltrials.gov Identifier: NCT00385671

Previous studies of the ex vivo lung have suggested significant intersubject variability in lung lobe geometry. A quantitative description of normal lung lobe shape would therefore have value in improving the discrimination between normal population variability in shape and pathology. To quantify normal human lobe shape variability, a principal component analysis (PCA) was performed on high resolution computed tomography (HRCT) imaging of the lung at full inspiration. Volumetric imaging from 22 never-smoking subjects (10 female and 12 male) with normal lung function was included in the analysis. For each subject, an initial finite element mesh geometry was generated from a group of manually selected nodes that were placed at distinct anatomical locations on the lung surface. Each mesh used cubic shape functions to describe the surface curvilinearity, and the mesh was fitted to surface data for each lobe. A PCA was performed on the surface meshes for each lobe. Nine principal components (PCs) were sufficient to capture >90% of the normal variation in each of the five lobes. The analysis shows that lobe size can explain between 20% and 50% of intersubject variability, depending on the lobe considered. Diaphragm shape was the next most significant intersubject difference. When the influence of lung size difference is removed, the angle of the fissures becomes the most significant shape difference, and the variability in relative lobe size becomes important. We also show how a lobe from an independent subject can be projected onto the study population’s PCs, demonstrating potential for abnormalities in lobar geometry to be defined in a quantitative manner.

Various alkoxy-substituted heterocyclic stannanes provide access to the corresponding substituted ‘pyridone’ moieties via Stille cross-coupling. Both pyridyl and a series of diazinyl stannanes are prepared, and options for unmasking (via demethylation or debenzylation) of the pyridone unit are evaluated.

We propose a new methodology for automated landmark detection for breast MR images that combines statistical shape modelling and template matching into a single framework. The method trains a statistical shape model (SSM) of breast skin surface using 30 manually labelled landmarks, followed by generation of template patches for each landmark. Template patches are matched across the unseen image to produce correlation maps. Correlation maps of the landmarks and the shape model are used to generate a first estimate of the landmarks referred to as “shape predicted landmarks”. These landmarks are refined using local maximum search in individual landmarks correlation maps. The algorithm was validated on 30 MR images using a leave-one-out approach. The results reveal that the method is robust and capable of localising landmarks with an error of 3.41 ± 2.10 mm.

The release of fatty acids from plasma triglycerides for tissue uptake is critically dependent on the enzyme lipoprotein lipase (LPL). Hydrolysis of plasma triglycerides by LPL can be disrupted by the protein angiopoietin-like 4 (ANGPTL4), and ANGPTL4 has been shown to inactivate LPL in vitro. However, in vivo LPL is often complexed to glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) on the surface of capillary endothelial cells. GPIHBP1 is responsible for trafficking LPL across capillary endothelial cells and anchors LPL to the capillary wall during lipolysis. How ANGPTL4 interacts with LPL in this context is not known. In this study, we investigated the interactions of ANGPTL4 with LPL-GPIHBP1 complexes on the surface of endothelial cells. We show that ANGPTL4 was capable of binding and inactivating LPL complexed to GPIHBP1 on the surface of endothelial cells. Once inactivated, LPL dissociated from GPIHBP1. We also show that ANGPTL4-inactivated LPL was incapable of binding GPIHBP1. ANGPTL4 was capable of binding, but not inactivating, LPL at 4 °C, suggesting that binding alone was not sufficient for ANGPTL4's inhibitory activity. We observed that although the N-terminal coiled-coil domain of ANGPTL4 by itself and full-length ANGPTL4 both bound with similar affinities to LPL, the N-terminal fragment was more potent in inactivating both free and GPIHBP1-bound LPL. These results led us to conclude that ANGPTL4 can both bind and inactivate LPL complexed to GPIHBP1 and that inactivation of LPL by ANGPTL4 greatly reduces the affinity of LPL for GPIHBP1. Background: Lipoprotein lipase (LPL) function is modified by interactions with its transporter GPIHBP1 and the inhibitor angiopoietin-like 4 (ANGPTL4). Results: ANGPTL4 inactivated GPIHBP1-bound LPL. Inactivated LPL could not bind GPIHBP1. Conclusion: ANGPTL4 inactivation of LPL reduces the affinity of LPL for GPIHBP1 causing dissociation. Significance: Understanding ANGPTL4's interactions with LPL in a physiological context is vital to clarifying ANGPTL4's role in triglyceride metabolism.

This study presents a method for estimating the spatial variations in material properties of elastic membranes, such as biological tissue, which contain both inhomogeneous strain fields and inhomogeneous material properties. In order to validate the method, an inhomogeneous, isotropic rubber membrane was biaxially loaded to obtain a set of states. A neo-Hookean finite element model, together with the measured strains, was used to estimate the material parameters by minimizing the residuals between the measured and modelled residual on surface tractions.

Various alkoxy-substituted heterocyclic stannanes provide access to the corresponding substituted ‘pyridone’ moieties via Stille cross-coupling. Both pyridyl and a series of diazinyl stannanes are prepared, and options for unmasking (via demethylation or debenzylation) of the pyridone unit are evaluated.

P53 allelic polymorphism at codon 72 has been studied as a possible predisposing factor for cervical carcinogenesis with inconsistent results. Storey and colleagues recently published the interesting finding of a 7-fold increased risk for cervical cancer in women homozygous for the arginine allele at codon 72. This stimulated a number of independent investigations, the majority of which found no association of cervical cancer and arginine homozygosity. With the use of a modified Storey method for determining codon 72 allelotypes, DNA was examined from 431 microdissected, formalin-fixed, archival cervical conization specimens ranging from low-grade squamous lesions to invasive cancer. An alternative independent method using restriction fragment length polymorphism analysis was performed on all arginine homozygotes and all indeterminate cases for confirmation and final allelotype assignment. With the use of Storey's method alone, logistic regression suggested an association (odds ratio, 1.42) between arginine homozygosity and invasive disease. However, with the use of the combined method for accurate allelotyping, this trend disappeared (odds ratio, 1.00), the discordance was clearly resolvable as being due to methodologic variables. With the use of two separate methods for codon 72 allelotyping and accounting for a number of the issues raised in previously published reports, there is no increased risk for invasive cervical cancer associated with arginine homozygosity at codon 72 of p53.

A study has been performed of the manner in which two structural features of poly(olefin sulfone)s, helical backbones and calamitic side chains, create order in films. For this purpose copolymers were prepared with one (polymer I) or two (polymer III) cyanobiphenyls per residue, and terpolymers were prepared with both such residues diluted to below the 5% level within an otherwise poly(eicosene sulfone) chain (respectively, polymers II and IV). The polymers all have ordered phases according to X-ray powder diffraction studies on samples cooled from the melt, a layer spacing of about 45 Å being detected in the films as in the bulk. Those polymers with mainly eicosene sulfone residues had crystalline phases with large domains, the layers deriving from the helical backbones alone, the smectic A phases of the parent poly(eicosene sulfone) being either suppressed or reduced in extent by the presence of the aromatic moieties, which were almost randomly orientated. Those with one or two cyanobiphenyls per residue were liquid crystalline. In the latter the layer spacing derives from both backbone and side chains and is reduced when the residues bear a second mesogen as a consequence of a constraining effect from the stiff backbone, as a novel model predicts. The spacers give rise to a glass transition and segregate the planes in which the stiff backbones are assembled from the regions in which the aromatic groups aggregate on account of the strong pi-pi interactions. Amorphous and optically isotropic spun cast films of these polymers became ordered on cooling from the melt or just on annealing, with the order, as determined by studies on the optical properties, being homeotropic for the aromatics and being planar for the backbones in a monodomain. For this arrangement we introduce the term homeo-planar smectic. Order parameters as high as 0.63 were measured for polymer I, from a clear film. The cyanobiphenyl chromophores formed H aggregates, with blue shifts in absorption and red shifts in fluoresence, and a little surprisingly these resulted in a circular dichroism, detectable when the films were inspected at an angle of 45 degrees to the normal.

Background Patients with multiple sclerosis (MS) often report neuropathic pain (NP-MS). The purpose of this study was to assess the efficacy and tolerability of duloxetine as treatment for NP-MS. Methods In this study, 239 adults with NP-MS (duloxetine = 118, placebo = 121) were randomized to duloxetine 60 mg (30 mg for 1 week, then 60 mg for 5 weeks) or placebo once daily for a 6-week acute therapy phase, followed by a 12-week open-label extension phase (duloxetine 30 to 120 mg/day). Eligible patients had MS for ≥ 1 year and a score ≥ 4 on daily average pain intensity (API) ratings for ≥ 4 of 7 days immediately before randomization. Patients rated API daily on an 11-point numeric scale (0 [no pain] to 10 [worst possible pain]) in an electronic diary. The primary efficacy measure, change in weekly API ratings, was analyzed longitudinally with a mixed-model repeated-measures analysis. Completion, reasons for discontinuation, and treatment-emergent adverse event incidence were compared by Fisher's exact test. Results Duloxetine-treated patients had statistically greater mean improvement in API vs. placebo at Week 6 (−1.83 vs. −1.07, P = 0.001). Treatment completion did not significantly differ between groups. Discontinuation due to adverse events was statistically greater for duloxetine vs. placebo (13.6% vs. 4.1%, P = 0.012). Decreased appetite was reported significantly more often by duloxetine-treated patients (5.9% vs. 0%, P = 0.007). Conclusions This study found analgesic efficacy of duloxetine for NP-MS. Duloxetine is not approved for treatment of this condition. The duloxetine safety profile of this study was consistent with the known profile in other patient populations.

The ocular lens generates an internal circulation in order to transport nutrients into the lens. The internal circulation enters at the poles and exits at the equator of the lens. This internal circulation is the result of the localization of membrane proteins and the cellular architecture of the lens. This work presents the development of a finite element model that solves the advection-diffusion equations for ion fluxes, the isotonic transport equations for water flux and the equations for transmembrane ion and water fluxes.

We present an automated image-to-mesh workflow that meshes the cortical surfaces of the human femur, from clinical CT images. A piecewise parametric mesh of the femoral surface is customized to the in-image femoral surface by an active shape model. Then, by using this mesh as a first approximation, we segment cortical surfaces via a model of cortical morphology and imaging characteristics. The mesh is then customized further to represent the segmented inner and outer cortical surfaces. We validate the accuracy of the resulting meshes against an established semi-automated method. Root mean square error for the inner and outer cortical meshes were 0.74 mm and 0.89 mm, respectively. Mean mesh thickness absolute error was 0.03 mm with a standard deviation of 0.60 mm. The proposed method produces meshes that are correspondent across subjects, making it suitable for automatic collection of cortical geometry for statistical shape analysis.