Pressure-Temperature Phase Diagram Reveals Spin-Lattice Interactions in Co[N(CN)2]2.

Diamond anvil cell techniques, synchrotron-based infrared and Raman spectroscopies, and lattice dynamics calculations are combined with prior magnetic property work to reveal the pressure-temperature phase diagram of Co[N(CN)2]2. The second-order structural boundaries converge on key areas of activity involving the spin state exposing how the pressure-induced local lattice distortions trigger the ferromagnetic → antiferromagnetic transition in this quantum material.

Magnetoelectric Coupling through the Spin Flop Transition in Ni_{3}TeO_{6}.

We combined high field optical spectroscopy and first principles calculations to analyze the electronic structure of Ni_{3}TeO_{6} across the 53 K and 9 T magnetic transitions, both of which are accompanied by large changes in electric polarization. The color properties are sensitive to magnetic order due to field-induced changes in the crystal field environment, with those around Ni1 and Ni2 most affected. These findings advance the understanding of magnetoelectric coupling in materials in which magnetic 3d centers coexist with nonmagnetic heavy chalcogenide cations.

High Pressure Vibrational Properties of WS2 Nanotubes.

We bring together synchrotron-based infrared and Raman spectroscopies, diamond anvil cell techniques, and an analysis of frequency shifts and lattice dynamics to unveil the vibrational properties of multiwall WS2 nanotubes under compression. While most of the vibrational modes display similar hardening trends, the Raman-active A1g breathing mode is almost twice as responsive, suggesting that the nanotube breakdown pathway under strain proceeds through this displacement. At the same time, the previously unexplored high pressure infrared response provides unexpected insight into the electronic properties of the multiwall WS2 tubes. The development of the localized absorption is fit to a percolation model, indicating that the nanotubes display a modest macroscopic conductivity due to hopping from tube to tube.

Size-dependent vibronic coupling in α-Fe2O3.

We report the discovery of finite length scale effects on vibronic coupling in nanoscale α-Fe2O3 as measured by the behavior of vibronically activated d-d on-site excitations of Fe(3+) as a function of size and shape. An oscillator strength analysis reveals that the frequency of the coupled symmetry-breaking phonon changes with size, a crossover that we analyze in terms of increasing three-dimensional character to the displacement pattern. These findings demonstrate the flexibility of mixing processes in confined systems and suggest a strategy for both enhancing and controlling charge-lattice interactions in other materials.

The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy.

Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection.

Molecular epidemiology of human Campylobacter jejuni shows association between seasonal and international patterns of disease.

We sought to explain seasonality and other aspects of Campylobacter jejuni epidemiology by integrating population genetic and epidemiological analysis in a large 3-year longitudinal, two-centre, population-based study. Epidemiological information was collected for 1505 isolates, which were multilocus sequence-typed. Analyses compared pathogen population structure between areas, over time, and between clinical presentations. Pooled analysis was performed with published international datasets. Subtype association with virulence was not observed. UK sites had nearly identical C. jejuni populations. A clade formed by ST45 and ST283 clonal complexes showed a summer peak. This clade was common in a Finnish dataset but not in New Zealand and Australian collections, countries with less marked seasonality. The UK, New Zealand and Australian collections were otherwise similar. These findings map to known in-vitro differences of this clade. This identifies a target for studies to elucidate the drivers of the summer peak in human C. jejuni infection.

Prevalence and risk factors for hepatitis C virus infection in Kech District, Balochistan, Pakistan: most infections remain unexplained. A cross-sectional study.

We studied a cross-sectional sample of the population of Kech, a small rural town in Pakistan to determine the prevalence and risk factors for hepatitis C infection. The prevalence of hepatitis C was 110 out of 2000 persons (5·5%, 95% confidence interval 4·5-6·5). Higher rates were identified in males. Independent risk factors identified were age ≥75 years, being a healthcare worker, and injecting drug use. There was a high prevalence of many potential routes of transmission of bloodborne viruses and most people reported at least one potential risk factor.

The Patient Health Questionnaire 12 Somatic Symptom scale as a predictor of symptom severity and consulting behaviour in patients with irritable bowel syndrome and symptomatic diverticular disease.

BACKGROUND: Anxiety, depression and nongastrointestinal symptoms are often prominent in irritable bowel syndrome (IBS), but their relative value in patient management has not been quantitatively assessed. We modified the Patient Health Questionnaire 15 (PHQ-15) by excluding three gastrointestinal items to create the PHQ-12 Somatic Symptom (PHQ-12 SS) scale. AIMS: To compare the value of the PHQ-12 SS scale with the Hospital Anxiety and Depression (HAD) scale in predicting symptoms and patient behaviour in IBS and diverticular disease. METHODS: We compared 151 healthy volunteers (HV), 319 IBS patients and 296 patients with diverticular disease (DD), 113 asymptomatic [ASYMPDD] and 173 symptomatic DD (SYMPDD). RESULTS: Patient Health Questionnaire 12 SS scores for IBS and SYMPDD were significantly higher than HV. Receiver-operator curves showed a PHQ-12 SS >6, gave a sensitivity for IBS of 66.4% with a specificity of 94.7% and a positive likelihood ratio (PLR) = 13.2, significantly better than that associated with an HAD anxiety score >7, PLR = 3.0 and depression score >7 PLR = 6.5. PHQ-12 SS correlated strongly with IBS severity scale and GP visits in both IBS and DD. CONCLUSION: The PHQ-12 SS scale is a useful clinical tool which correlates with patient behaviour in both IBS and symptomatic DD.

Autoantibodies in chronic hepatitis C virus infection and their association with disease profile.

Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain. We assessed the prevalence of anti-nuclear (ANA) and anti-smooth muscle (ASM) antibodies within a cohort of 963 treatment-naïve HCV patients. We also assessed for differences between autoantibody-positive and autoantibody-negative patients in demographics, markers of disease activity and response to anti-viral treatment. One hundred and seventy-two patients (17.9%) had at least one autoantibody, of which were 104 (10.8%) ASM, 54 (5.6%) ANA and 14 (1.5%) positive for both. Autoantibody-positive patients were older (43 vs 39 years, P = 0.001) caused by an age-related increase in ANA (but not ASM). There were no differences in gender, alcohol intake, ethnicity or viral genotype. The presence of autoantibodies, and specifically ASM, was associated with an increase in interface hepatitis score amongst men (1.1 vs 0.8, P = 0.005) but no difference in other necroinflammatory measures, liver function tests or immunoglobulins (Ig). There was no difference in initial fibrosis stage or rate of fibrosis progression. Autoantibodies did not affect response to anti-viral treatment. We conclude that autoantibodies are frequent in HCV infection. Anti-nuclear antibodies increase with age, whereas ASM antibodies are associated with interface hepatitis in men. Neither autoantibody carries increased risk of fibrosis progression or failure of therapy.

Psychological and colonic factors in painful diverticulosis.

BACKGROUND: The importance of psychological factors in symptom expression in diverticulosis is unknown. This follow-up study assessed the relative importance of colonic and psychological factors in symptom expression. METHODS: Patients with barium enema-proven diverticula were sent a bowel symptom questionnaire in 1999 and again in 2006 with additional psychological questionnaires included. RESULTS: Some 170 of 261 initial responders were eligible for follow-up and 124 (72.9 per cent) provided complete replies. Forty-two (33.9 per cent) of 124 respondents experienced recurrent abdominal pain a median of 3.5 (interquartile range (i.q.r.) 2.00-9.25) days per month, with a median duration of 1 (i.q.r. 0.7-2) h. Multivariable analysis identified a history of acute diverticulitis (odds ratio 3.98; P = 0.010) and a raised score on the Hospital Anxiety and Depression Scale (odds ratio 2.53; P = 0.030) as the best predictors of recurrent pain. CONCLUSION: Psychological and colonic factors are important in symptom expression in diverticulosis.

Clinical pathways for patients with newly diagnosed hepatitis C - what actually happens.

Management of hepatitis C virus (HCV)-infected individuals requires referral to specialist care. To determine whether patients newly diagnosed as anti-HCV positive are appropriately referred for further investigation and management, and if not, to determine why not. We studied patients tested for antibodies to HCV by Nottingham Public Health Laboratory in a 2-year period (2000-2002). The progress of newly diagnosed anti-HCV positive patients into specialist clinics for further management was documented. For patients not referred for specialist care, a questionnaire was sent to the clinician requesting the initial anti-HCV test, to identify reasons for nonreferral. Eleven thousand one hundred and seventy-seven patients were tested for anti-HCV. Two hundred and fifty-six (2.3%) were newly diagnosed as being anti-HCV positive. Two per cent of samples sent from primary care were anti-HCV positive, compared to 18.8, 18.9 and 1.3% sent from prison, drug and alcohol units, and secondary care, respectively. About 64.3% of positive patients diagnosed in primary care were referred to specialist care, compared to 18.4, 42.4 and 62.6% of patients diagnosed in the other three settings. One hundred and twenty-five (49%) newly diagnosed patients were referred appropriately for further management. 68 of these attended clinic, 45 underwent liver biopsy and 26 (10%) began treatment. One hundred and thirty-one patients (51%) were not referred. In 54 cases, there was no evidence that the anti-HCV positive result reached the patient. In 15, referral was considered but rejected, and 20 patients were referred to non-HCV-specialists (their general practitioners or to genito-urinary medicine). Hence less than 50% of newly diagnosed anti-HCV positive patients are referred to an appropriate clinic for further investigation and management. Reasons for this are multifarious and complex, reflecting both systems failure and patient choice. Unless these are understood and addressed, the Department of Health Hepatitis C Strategy (2002) and Action Plan for England (2004) will fail to achieve their intended objectives.

Relationships between structural and functional measures of nutritional status in a normally nourished population.

BACKGROUND AND AIMS: Both anthropometric and functional measurements have been used in nutritional assessment and monitoring. Hand dynamometry is a predictor of surgical outcome and peak expiratory flow rate has been used as an index of respiratory muscle function. This study aims to measure in normal subjects the relationship between anthropometric measurements, voluntary muscle strength by hand grip dynamometry and respiratory muscle function by peak expiratory flow rate. METHODS: Ninety-eight subjects (46 male, 52 female) with a mean age of 45.9 years were studied. Hand grip strength was measured in the dominant and non-dominant hands with a portable strain-gauge dynamometer. Peak expiratory flow rate was measured using a mini-Wright peak flow meter. Three readings were taken, each 1 min apart, and the average recorded. Midarm muscle circumference (MAMC) was derived from triceps skin fold thickness and midarm circumference (MAC) using standard anthropometric techniques. Statistical relationships were measured with Pearson's coefficient of correlation. RESULTS: In both sexes there was significant correlation between hand grip strength in the dominant and non-dominant hands and peak expiratory flow rate (P<0.001). In men, there was a positive correlation between MAMC, hand grip strength (P<0.001) and peak expiratory flow rate (P<0.001). In women muscle function correlated with height (P<0.001) but not MAMC (P>0.05). CONCLUSIONS: In normal subjects bedside tests of skeletal and respiratory muscle function correlated with each other in both sexes, and with muscle mass in men but not in women.

Human papillomavirus infection in women who develop high-grade cervical intraepithelial neoplasia or cervical cancer: a case-control study in the UK.

Human papillomavirus (HPV) testing might identify older women who could be withdrawn from the cervical screening programme, or require less frequent screening. A case-control study using the United Kingdom cervical screening population was set up to help address this issue. Cases comprised 575 women who developed cervical intraepithelial neoplasia (CIN) grade 2 or worse over a 13-year period following a cytologically normal baseline smear, and were stratified by age group ('under 20', '20-39' and 40 years or over). Controls (n=601) were women who remained disease free over this interval and were the same age on average as cases. DNA was extracted from the baseline smears and tested for HPV by PCR using GP5+/6+ consensus primers. HPV+ samples were tested for HPV types 16 and 18 using specific PCR primers. In all, 27.0% of cases tested positive for HPV at baseline, compared with 15.4% of controls (odds ratio (OR)=2.00; 95% confidence interval (CI), 1.50-2.68). Among women aged 40 years or over, the OR for HPV 16 was 8.95 (95% CI, 2.63-30.4). These results support the need for further cervical screening of HPV- older women, as many of the cases were HPV- at baseline.

A practical posture for hand grip dynamometry in the clinical setting.

BACKGROUND & AIMS: The optimal testing position for hand grip strength, which is a useful functional measure of nutritional status, is open to debate. We therefore examined the systematic difference between different postures in order to establish a methodology that is clinically relevant, easy to perform and reproducible. METHODS: Grip strength was measured in the dominant and non-dominant hands with a strain gauge dynamometer in three positions: lying at 30 degrees in bed with elbows supported, seated in an armchair with elbows supported and in a chair with elbows unsupported. The average of three readings made in each position, each 1 min apart, was recorded. RESULTS: 55 normally nourished subjects (26 male) were studied. Mean (95% CI) grip strengths measured in the dominant hand with the subject in bed, sitting in an armchair and sitting in a chair were 45.7 (42.3-49.2), 46.3 (42.9-49.8) and 48.5 (45.4-51.7) kg, respectively for males. Corresponding values for females were 29.4 (27.0-31.8), 29.3 (26.8-31.9) and 31.6 (28.8-34.3) kg. There was no significant difference (Student t-paired test) between measurements made in bed and on an armchair (P = 0.49), but the measurements made in a chair were significantly higher than those made in bed (P = 0.001) and in an armchair (P = 0.004). No statistical difference was present, comparing the three separate measurements in each position (Student t-paired test). CONCLUSIONS: Measurement of grip strength using hand dynamometry is reproducible and consistent. As all patients are not able to sit in a chair with elbows unsupported, in clinical practice it is more practicable to perform hand dynamometry with the elbows supported in a bed or armchair.

Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study.

BACKGROUND: The natural history of hepatitis C virus (HCV) infection remains uncertain. Previous data concerning rates of progression are from studies using estimated dates of infection and single liver biopsy scores. We prospectively studied the rate of progression of fibrosis in HCV infected patients by repeat liver biopsies without intervening treatment. PATIENTS: We studied 214 HCV infected patients (126 male; median age 36 years (range 5-8)) with predominantly mild liver disease who were prospectively followed without treatment and assessed for risk factors for progression of liver disease. Interbiopsy interval was a median of 2.5 years. Paired biopsies from the same patient were scored by the same pathologist. RESULTS: Seventy of 219 (33%) patients showed progression of at least 1 fibrosis point in the Ishak score; 23 progressed at least 2 points. Independent predictors of progression were age at first biopsy and any fibrosis on first biopsy. Factors not associated with progression were: necroinflammation, duration of infection, alcohol consumption, alanine aminotransferase levels, current or past hepatitis B virus infection, ferritin, HCV genotype, and steatosis or iron deposition in the initial biopsy. CONCLUSIONS: One third of patients with predominantly mild hepatitis C showed significant fibrosis progression over a median period of 30 months. Histologically, mild hepatitis C is a progressive disease. The overall rate of fibrosis progression in patients with hepatitis C was low but increased in patients who were older or had fibrosis on their index biopsy. These data suggest that HCV infection will place an increasing burden on health care services in the next 20 years.

Randomized, double-blind, placebo-controlled trial of prednisolone in post-infectious irritable bowel syndrome.

BACKGROUND: Post-infectious irritable bowel syndrome is associated with increased serotonin-containing enterochromaffin cells and lymphocytes in rectal biopsies. Animal studies have suggested that steroids reduce the lymphocyte response and suppress some of the post-infectious changes in neuromuscular function. AIM: To evaluate whether steroids reduce the number of enterochromaffin cells and improve the symptoms of post-infectious irritable bowel syndrome. METHODS: Twenty-nine patients with post-infectious irritable bowel syndrome underwent a randomized, double-blind, placebo-controlled trial of 3 weeks of oral prednisolone, 30 mg/day. Mucosal enterochromaffin cells, T lymphocytes and mast cells were assessed in rectal biopsies before and after treatment, and bowel symptoms were recorded in a daily diary. RESULTS: Initial enterochromaffin cell counts were increased and correlated with initial lamina propria T-lymphocyte counts (r = 0.460, P = 0.014). Enterochromaffin cell counts did not change significantly after either prednisolone (- 0.8% +/- 9.2%) or placebo (7.9% +/- 7.9%) (P = 0.5). Although lamina propria T-lymphocyte counts decreased significantly after prednisolone (22.0% +/- 5.6%, P = 0.003), but not after placebo (11.5% +/- 8.6%, P = 0.1), this was not associated with any significant treatment-related improvement in abdominal pain, diarrhoea, frequency or urgency. CONCLUSIONS: Prednisolone does not appear to reduce the number of enterochromaffin cells or cause an improvement in symptoms in post-infectious irritable bowel syndrome. Other approaches to this persistent condition are indicated.

Risk factors for drug resistant tuberculosis in Leicestershire--poor adherence to treatment remains an important cause of resistance.

In the light of rising numbers of tuberculosis (TB) cases in the United Kingdom, the problem of anti-tubercular drug resistance remains a significant concern. Drug resistant TB cases are more difficult and costly to treat, and require appropriate treatment and control mechanisms. This matched case control study aimed to investigate risk factors for resistance in Leicestershire, using data for laboratory isolates of Mycobacterium tuberculosis identified from 1993 to 1998. Each case, defined as culture positive laboratory isolates resistant to at least one first-line drug, was matched to four fully sensitive controls on age, sex and ethnic group. Twenty-three cases and 81 controls were included in the analysis. Drug resistance in Leicestershire was found to be associated with poor adherence to treatment (OR 4.8, 95% CI 1.6-14.4, P=0.005) and with previous TB (OR 3.7, 95% CI 1.2-11.8, P=0.022). These findings emphasize the need to provide support to patients taking treatment in order to maximize adherence.

Prognosis in post-infective irritable bowel syndrome: a six year follow up study.

BACKGROUND: Irritable bowel syndrome developing following infective gastroenteritis accounts for approximately 1 in 10 of unselected IBS patients. AIMS: To define the long term natural history of post-infective IBS (PI-IBS). METHODS: A total of 436 individuals, who had previously responded to a questionnaire on their bowel habits following an acute episode of gastroenteritis, were sent a questionnaire about their current bowel habits and physical and mental health six years after their initial illness. RESULTS: Complete data on original bowel habit, episodes of gastroenteritis, mental health history, and subsequent bowel habit at six years were obtained in 192 individuals. Of these, there were 14 cases of "post-infective IBS" (PI-IBS) and 13 who had IBS prior to infection (previous IBS). Over the six year follow up period there were 20 "new non-infective IBS cases" (new IBS). The strongest risk factor for developing any type of IBS was female sex (relative risk 2.2, p<0.05). Compared with new IBS, those with PI-IBS had significantly more days with loose stools (p<0.05) but a similar number of days with pain, urgency, and bloating. Six of 14 (43%) PI-IBS and four of 13 (31%) previous IBS patients recovered by six years (NS). Of 27 IBS patients followed for six years, only 1/8 with a history of anxiety or depression recovered compared with 9/19 without such a history (p=0.19). CONCLUSION: PI-IBS differs from non-infective IBS by having more diarrhoeal features. Less than half of both PI-IBS and non-infective IBS cases recover over six years. A history of anxiety and depression severe enough to warrant treatment may impair recovery but larger numbers are needed to prove this.

Peri-operative fluid and electrolyte management: a survey of consultant surgeons in the UK.

BACKGROUND: Current peri-operative fluid and electrolyte management in the UK may be suboptimal. We assessed the attitudes of consultant surgeons to fluid and electrolyte prescribing and gathered suggestions for improvement in education on the subject. METHODS: A postal questionnaire survey was sent to 1091 Fellows of the Association of Surgeons of Great Britain and Ireland. Of the 730 (67%) replies, 20 were invalid or incomplete, and 710 (65%) questionnaires were analysed. Outcome measures included provision of guidelines and teaching to junior staff on fluid and electrolyte prescribing, appropriateness of fluid management and suggestions to improve standards. RESULTS: Junior staff were given written guidelines in 22% of instances. Only 16% of respondents felt that their preregistration house officers (PRHOs) were adequately trained in the subject before joining the firm; 15% also stated that PRHOs did not receive much training on their firm. 65% felt that fluid balance charts were accurately maintained, nursing shortages being the commonest reason for inaccuracies. Only 30% felt that postoperative patients were receiving appropriate amounts of water, sodium and potassium. Respondents who had been consultants for > 5 years were more likely to prefer erring on the side of under-replacement of fluid than those who were consultants for 5 years (63% versus 47%, P < 0.0005). Suggestions for improvement in education included problem-oriented ward rounds, written guidelines, and discussion of patient scenarios. CONCLUSIONS: Consultant surgeons feel that present practice in peri-operative fluid management is unsatisfactory. Higher standards within clinical governance and risk management may be achieved by focused practical training combined with formal written guidelines.

Congenital coronary arteriovenous fistula presenting with syncope.

Previous reports of syncope in patients with coronary arteriovenous fistula (CAVF) have theorized that it occurs secondary to a coronary steal phenomenon. We present a case of syncope in a young woman with a CAVF and no anatomic substrate for coronary steal.