Experimental observation of negative capacitance in ferroelectrics at room temperature.

Effective negative capacitance has been postulated in ferroelectrics because there is a hysteresis in plots of polarization-electric field. Compelling experimental evidence of effective negative capacitance is presented here at room temperature in engineered devices, where it is stabilized by the presence of a paraelectric material. In future integrated circuits, the incorporation of such negative capacitance into MOSFET gate stacks would reduce the subthreshold slope, enabling low power operation and reduced self-heating.

Treatment referral before and after the introduction of the Liverpool Patients Concerns Inventory (PCI) into routine head and neck oncology outpatient clinics.

PURPOSE: Holistic needs assessment is a key recommendation in improving supportive and palliative care in adults with cancer. The Patients Concerns Inventory (PCI) is a holistic needs assessment tool designed for head and neck cancer survivors in outpatient setting. Routine screening of potential unmet needs in a clinic may result in increased onward referrals, thus placing a burden on existing healthcare services. The aim of this study was to compare the referral trends following consultation in the time periods before and after introduction of PCI in an oncology outpatient clinic. METHOD: A cross-sectional cohort of disease-free survivors of oral/oropharyngeal cancers of a single consultant was prospectively exposed to PCI from July 2007 to April 2009. The PCI is a self-completed questionnaire consisting of 55 items of patient needs/concern and a list of multidisciplinary professionals, whom patients may wish to talk to or be referred to. Retrospective analysis of referral patterns from clinic letters in two periods in the pre-PCI and post-PCI exposure was performed. Prospective analysis of consultations was performed to determine the outcome of PCI-highlighted items. RESULTS: There was no change in the prevalence of onward referral with the introduction of PCI, i.e. 21 referrals per 100 patients seen in outpatients. However, the proportion of referrals to oral rehabilitation and psychological support increased. Referrals to certain services, e.g. speech and language and dentistry, remained consistently in demand. Many PCI-highlighted needs were dealt in a clinic with by the consultant and/or other professionals during a multidisciplinary consultation. CONCLUSIONS: Routine use of PCI promotes target efficiency by directing and apportioning appropriate services to meet the needs for supportive care of head and neck cancer survivors.

R3F, a novel membrane-associated glycogen targeting subunit of protein phosphatase 1 regulates glycogen synthase in astrocytoma cells in response to glucose and extracellular signals.

Abnormal regulation of brain glycogen metabolism is believed to underlie insulin-induced hypoglycaemia, which may be serious or fatal in diabetic patients on insulin therapy. A key regulator of glycogen levels is glycogen targeted protein phosphatase 1 (PP1), which dephosphorylates and activates glycogen synthase (GS) leading to an increase in glycogen synthesis. In this study, we show that the gene PPP1R3F expresses a glycogen-binding protein (R3F) of 82.8 kDa, present at the high levels in rodent brain. R3F binds to PP1 through a classical 'RVxF' binding motif and substitution of Phe39 for Ala in this motif abrogates PP1 binding. A hydrophobic domain at the carboxy-terminus of R3F has similarities to the putative membrane binding domain near the carboxy-terminus of striated muscle glycogen targeting subunit G(M)/R(GL), and R3F is shown to bind not only to glycogen but also to membranes. GS interacts with PP1-R3F and is hyperphosphorylated at glycogen synthase kinase-3 sites (Ser640 and Ser644) when bound to R3F(Phe39Ala). Deprivation of glucose or stimulation with adenosine or noradrenaline leads to an increased phosphorylation of PP1-R3F bound GS at Ser640 and Ser644 curtailing glycogen synthesis and facilitating glycogen degradation to provide glucose in astrocytoma cells. Adenosine stimulation also modulates phosphorylation of R3F at Ser14/Ser18.

Computed tomography of the brain in the emergency department: how often is tracheal intubation and general anaesthesia required?

As a result of national guidance in the UK, the number of computed tomography brains performed in patients with minor head injury has increased significantly. The aim of this survey was to establish the requirement for general anaesthesia and tracheal intubation in the management of emergency department patients requiring an urgent computed tomography of the brain. About 300 consecutive scans in emergency department patients were reviewed. The majority (>90%) did not require anaesthetic airway management despite an overall acute scan diagnosis rate of around 25% and 30 day mortality of 10%.

Computational modelling of lung injury: is there potential for benefit?

State-of-the-art medical care of the victims of current conflicts is generating large quantities of quality clinical data as a by-product. Observational research based on these data is beginning to have a profound influence on the clinical management of both military and civilian trauma patients. Computational modelling based on these datasets may offer the ability to investigate clinical treatment strategies that are practically, ethically or scientifically impossible to investigate on the front line. This article reviews the potential of this novel technology to aid development of treatment for blast lung and other unresolved medical scenarios.

Women's policy networks and the Infanticide Act 1922.

This article examines the reason for the passage of the 1922 Infanticide Act, arguing that it owes much to the influence and work of women's policy networks. Historians have disagreed as to why the Act was passed with relative suddenness in the early 1920s, at a time when infanticide was generally considered a much less pressing social issue than it had been in Victorian England. Moreover, several Bills brought between 1908 and 1913 proposing that the law on this subject be amended so that women who killed their newborns no longer faced the death penalty had all failed. Importantly, the roles of juror and lay magistrate had become open to women in 1920, following the passage of the Sex Disqualification (Removal) Act 1919. The public interest generated by a case of newborn murder tried at the Leicester Assizes in 1921 (particularly amongst women's organizations, including the suffragette group the Women's Freedom League) led several leading women with political connections to push for a change in the law. Without the pressure these women could bring to bear on civil servants and politicians, attempts to bring in new legislation on infanticide would have been postponed well into the twentieth century.

Agenesis of lung - a report of two cases.

Agenesis of lung is a rare congenital disorder. We are reporting varied degree of pulmonary agenesis in two adult patients.

Human bone collagen synthesis is a rapid, nutritionally modulated process.

UNLABELLED: We developed a direct assay of human bone collagen synthesis using [13C] or [15N] proline and applied it to determine the effects of feeding in young healthy men. Surprisingly, postabsorptive bone collagen synthesis is not sluggish, being approximately 0.07%/h more rapid than that of muscle protein, and capable of being stimulated within 4 h of intravenous feeding by 66 +/- 13%. INTRODUCTION: All current methods for estimation of bone collagen turnover are indirect, depending on the assay of collagen "markers." Our aim was to develop a direct method for human bone collagen synthesis to be used to study its physiology and pathology, and specifically, in the first instance, the effect of feeding. MATERIALS AND METHODS: We applied, over 2 h, flooding doses of [13C] and [15N] proline to label iliac crest bone collagen in eight young healthy men. The rate of collagen synthesis was determined as the rate of labeling of collagen hydroxyproline (assayed by gas chromatography-combustion-isotope ratio mass spectrometry in collagen extracted by differential solubility) compared with plasma proline labeling (assayed by gas chromatography-mass spectrometry). We also determined (in a second group of eight young healthy men) the effect of intravenous nutrition (glucose, lipid emulsion, and amino acids (in the ratio of 55%:30%:15% energy, respectively). RESULTS: Free bone proline labeling was 92 +/- 6% of that of plasma proline, supporting the flooding dose assumption. Human iliac crest bone collagen is heterogeneous, with NaCl-EDTA, 0.5 M acetic acid, pepsin-acetic acid, and hot water-extractable pools being responsible for approximately 1%, 3%, 8%, and 81% of content, respectively. The synthetic rates were 0.58 +/- 0.1, 0.24 +/- 0.05, 0.07 +/- 0.02, and 0.06 +/- 0.01%/h, respectively, giving an average rate of approximately 0.066%/h. [13C] and [15N] proline gave identical results. Intravenous nutrition caused the disappearance of proline label from the procollagen pool and its increased appearance in the less extractable pools, suggesting nutritional stimulation of collagen processing. CONCLUSION: The results show (1) that iliac crest bone collagen synthesis is faster than generally assumed and of the same order as muscle protein turnover and (2) that feeding increases synthesis by approximately 66%. Given its ability to detect physiologically meaningful responses, the method should provide a new approach to studying the regulation of bone collagen turnover.

No effect of creatine supplementation on human myofibrillar and sarcoplasmic protein synthesis after resistance exercise.

Muscle hypertrophy during resistance training is reportedly increased by creatine supplementation. Having previously failed to find an anabolic effect on muscle protein turnover at rest, either fed or fasted, we have now examined the possibility of a stimulatory effect of creatine in conjunction with acute resistance exercise. Seven healthy men (body mass index, 23 +/- 2 kg/m2, 21 +/- 1 yr, means +/- SE) performed 20 x 10 repetitions of leg extension-flexion at 75% one-repetition maximum in one leg, on two occasions, 4 wk apart, before and after ingesting 21 g/day creatine for 5 days. The subjects ate approximately 21 g maltodextrin + 6 g protein/h for 3 h postexercise. We measured incorporation of [1-13C]leucine into quadriceps muscle proteins in the rested and exercised legs. Leg protein breakdown (as dilution of [2H5]phenylalanine) was also assessed in the exercised and rested leg postexercise. Creatine supplementation increased muscle total creatine by approximately 21% (P < 0.01). Exercise increased the synthetic rates of myofibrillar and sarcoplasmic proteins by two- to threefold (P < 0.05), and leg phenylalanine balance became more positive, but creatine was without any anabolic effect.

Human skeletal muscle expresses a glycogen-targeting subunit of PP1 that is identical to the insulin-sensitive glycogen-targeting subunit G(L) of liver.

Insulin has been previously shown to regulate the expression of the hepatic glycogen-targeting subunit, G(L), of protein phosphatase 1 (PP1) and is believed to control the activity of the PP1-G(L) complex by modulation of the level of phosphorylase a, which allosterically inhibits the activity of PP1-G(L). These mechanisms contribute to the ability of insulin to increase hepatic glycogen synthesis. Human G(L) shows >88% amino acid identity to its rat and mouse homologs, with complete conservation of the phosphorylase a binding site. G(L) is highly expressed in the liver and present at appreciable levels in heart tissue of all three species. Surprisingly, G(L) is highly expressed in human skeletal muscle while only being detected at very low levels in rat, mouse, and rabbit skeletal muscle. The amino acid sequence of G(L) predicted from the cDNA is identical in human liver and skeletal muscle and encoded by a gene on chromosome 8 at p23.1. The species-specific difference in the level of expression of G(L) mRNA and protein in skeletal muscle has important implications for understanding the mechanisms by which insulin regulates glycogen synthesis in human skeletal muscle and for questions regarding whether rodents are appropriate models for this purpose.

Metformin and insulin: is there a role for combination therapy?

OBJECTIVE: To review the literature on concomitant insulin and metformin therapy in patients with type 1 diabetes to determine the potential for combination therapy. DATA SOURCES: A MEDLINE and bibliographic search (1966-1996) of the literature pertaining to metformin and phenformin and their combined use with insulin in the treatment of patients with type 1 diabetes mellitus was performed. STUDY SELECTION: All human studies using metformin with insulin were included in the analysis. Studies using phenformin with insulin were also included due to its similarities to metformin. DATA SYNTHESIS: The recent availability of metformin provides some new options for treating diabetes mellitus. One possibility is the use of this medication in conjunction with insulin in patients with type 1 diabetes. Although this seems like a potentially beneficial combination, there is currently no recommendation for use in this manner. Experience with combination metformin and insulin therapy has consistently demonstrated a reduction in insulin requirements. Studies have not been of necessary size or duration to definitively prove the benefits of this insulin dose reduction or any other benefits of combination therapy. CONCLUSIONS: When metformin is added to insulin therapy, insulin requirements are likely to decrease. Although one would anticipate benefits from reduction in circulating insulin concentrations, the studies do not provide data to determine if benefits of combination therapy outweigh risks. Further studies of larger size and longer duration are needed before the use of metformin with insulin can be routinely recommended in patients with type 1 diabetes.

Extrapyramidal symptoms associated with calcium-channel blockers.

Flunarizine and cinnarizine have been well documented to cause EPS. Other CCBs, on rare occasions, also have been reported to cause EPS. Theoretical explanations for these events include the inhibition of calcium influx into striatal cells and direct dopaminergic antagonistic properties. In addition, the chemical structures of flunarizine and cinnarizine, which are related to neuroleptics, may explain the relatively greater incidence of EPS with these agents. Suggested risk factors for acquiring EPS with flunarizine or cinnarizine use appear to be age, although experience with using these agents in younger patients is limited, and a family history of tremors and/or Parkinson's disease. The onset and type of presentation is unpredictable and, in most instances, discontinuation of the medication relieves the symptoms within a few days to months. Pharmacologic management of EPS with continued use of the offending agent generally has not been of clinical benefit. In conclusion, patients receiving CCBs, particularly flunarizine and cinnarizine, should be monitored for EPS.

Synthesis of sweet-tasting methylthio derivatives of D-fructose and sucrose.

1,6-Di-S-methyl-1,6-dithio-D-fructofuranose and its bis(S-oxide) and bis(S,S-dioxide) are described. On examination for sweetness, the oxygenated compounds were neutral but the parent compound was 15-20 times sweeter than sucrose, and 1',6'-di-S-methyl-1',6'-dithiosucrose was slightly less sweet than sucrose.

Enhanced detection of preinvasive breast cancer: combined role of mammography and needle localization biopsy.

Several recent reports have described an increase in the incidence of preinvasive carcinoma of the breast. To determine the incidence of preinvasive breast cancer at our institution, the results of 469 consecutive outpatient breast biopsies performed at Walter Reed Army Medical Center between July 1, 1985, and January 1, 1987, were reviewed. During this time period, 256 biopsies were performed on palpable masses, and 213 needle localization biopsies were performed on mammographically suspicious lesions. The overall incidence of cancer was 15.4%. Needle localization biopsies yielded a diagnosis of cancer in 17.8% of cases, as did 13.3% of biopsies performed on palpable masses. Eight of 38 (21.1%) carcinomas identified by mammography were preinvasive at the time of diagnosis. Only one of 34 (2.9%) cancers identified because of a breast mass was preinvasive. We conclude that screening mammography is an invaluable tool for the detection of preinvasive carcinoma of the breast and that the increased use of mammography will result in an increase in the incidence of detection of this lesion.

Synthesis of 3-C-(hydroxymethyl)erythritol and 3-C-methylerythritol.

3-C-(Hydroxymethyl)erythritol was prepared from 3-C-(hydroxymethyl)-2,3-O-isopropylidene-D-erythro-tetrofuranose (4) by hydrolysis followed by reduction, or by reduction followed by hydrolysis. Monotosylation of 4, followed by reduction with lithium aluminum hydride and hydrolysis, afforded 3-C-methylerythritol.

An approach to leprosy work in south Bombay--a preliminary communication.

The city of Bombay with its teeming eight million citizens is characterised by varied types of living pattern in its different parts and the approach to leprosy control work should be flexible to suit these facets of living conditions. Earlier reports (Ganapati and Girija 1979) have indicated the possibility of the successful application of techniques based on mass surveys in North Bombay where people belonging to low socio-economic strata live in somewhat organised slums or shanty towns. However, extreme South Bombay is marked by the paucity of such vast slums and one is struck by the more permanent multistoreyed housing structures. Living in commercial establishments as well as footpath dwelling are common. This presentation consists of an attempt to gauge the leprosy problems in this part of the city taking advantage of 425 patients registered at a leprosy clinic run in conjunction with the dermatology out patient department of a big general hospital over a period of 40 months. 212 cases (50%) hailing from South Bombay proper were the subject matter for analysis. 66% (140) belonged to progressive types of leprosy classifiable as BT through LL and of the Ridley-Jopling classification and 30.7% were bacteriologically positive. 42.9% of the patients had some degree of deformity. Males formed 80% of the sample and 76% were above 15 years of age. Analysis of duration of residence revealed that 68% were living in Bombay for over six years and 53.5% were residing in the city for 11 years or more. This finding is contrary to the expectation of leprosy patients in Bombay belonging to a "floating population". Attempts at field work revealed the following findings: Slum pockets being few (only four), patients were expected to live in residential buildings; but it was found that 25% of population were staying in work places. 17% were footpath dwellers and 18.9% shared their accommodation with people other than family members. 10.4% were domestic servants staying in the residences of their employees. The labour class constituted 50.5% the unemployed housewives group formed 21.7% and beggers 0.9%. 4.2% only were slum dwellers. Locating and examining contacts of patients was difficult as 42.9% could not be traced owing to faulty addresses or patients having changed residences or shifted to native places. Of the 111 patients (52.3%) contacted, 26.4% were living with families and 26.1% were staying alone or with others.(ABSTRACT TRUNCATED AT 400 WORDS)