The first case of HIV-2 in Scotland.

HIV-1 infects an estimated 37 million people worldwide, while the rarer HIV-2 infects 1-2 million worldwide. HIV-2 is mainly restricted to West African countries. The majority of patients in Scotland are diagnosed with HIV-1, but in 2013 the West of Scotland Specialist Virology Centre (WoSSVC) diagnosed Scotland's first HIV-2 positive case in a patient from Côte d'Ivoire. HIV-2 differs from HIV-1 in terms of structural viral proteins, viral transmissibility, prolonged period of latency, intrinsic resistance to certain antivirals and how to monitor the effectiveness of treatment. Over the course of 5 years the patient has required several changes in treatment due to both side effects and pill burden. This case highlights the complexity of HIV-2 patient management over time.

Retraction Note: Oscillations of the baseline of solar magnetic field and solar irradiance on a millennial timescale.

This article has been retracted.

Oscillations of the baseline of solar magnetic field and solar irradiance on a millennial timescale.

Recently discovered long-term oscillations of the solar background magnetic field associated with double dynamo waves generated in inner and outer layers of the Sun indicate that the solar activity is heading in the next three decades (2019-2055) to a Modern grand minimum similar to Maunder one. On the other hand, a reconstruction of solar total irradiance suggests that since the Maunder minimum there is an increase in the cycle-averaged total solar irradiance (TSI) by a value of about 1-1.5 Wm-2 closely correlated with an increase of the baseline (average) terrestrial temperature. In order to understand these two opposite trends, we calculated the double dynamo summary curve of magnetic field variations backward one hundred thousand years allowing us to confirm strong oscillations of solar activity in regular (11 year) and recently reported grand (350-400 year) solar cycles caused by actions of the double solar dynamo. In addition, oscillations of the baseline (zero-line) of magnetic field with a period of 1950 ± 95 years (a super-grand cycle) are discovered by applying a running averaging filter to suppress large-scale oscillations of 11 year cycles. Latest minimum of the baseline oscillations is found to coincide with the grand solar minimum (the Maunder minimum) occurred before the current super-grand cycle start. Since then the baseline magnitude became slowly increasing towards its maximum at 2600 to be followed by its decrease and minimum at ~3700. These oscillations of the baseline solar magnetic field are found associated with a long-term solar inertial motion about the barycenter of the solar system and closely linked to an increase of solar irradiance and terrestrial temperature in the past two centuries. This trend is anticipated to continue in the next six centuries that can lead to a further natural increase of the terrestrial temperature by more than 2.5 °C by 2600.

Heartbeat of the Sun from Principal Component Analysis and prediction of solar activity on a millenium timescale.

We derive two principal components (PCs) of temporal magnetic field variations over the solar cycles 21-24 from full disk magnetograms covering about 39% of data variance, with σ = 0.67. These PCs are attributed to two main magnetic waves travelling from the opposite hemispheres with close frequencies and increasing phase shift. Using symbolic regression analysis we also derive mathematical formulae for these waves and calculate their summary curve which we show is linked to solar activity index. Extrapolation of the PCs backward for 800 years reveals the two 350-year grand cycles superimposed on 22 year-cycles with the features showing a remarkable resemblance to sunspot activity reported in the past including the Maunder and Dalton minimum. The summary curve calculated for the next millennium predicts further three grand cycles with the closest grand minimum occurring in the forthcoming cycles 26-27 with the two magnetic field waves separating into the opposite hemispheres leading to strongly reduced solar activity. These grand cycle variations are probed by α - Ω dynamo model with meridional circulation. Dynamo waves are found generated with close frequencies whose interaction leads to beating effects responsible for the grand cycles (350-400 years) superimposed on a standard 22 year cycle. This approach opens a new era in investigation and confident prediction of solar activity on a millenium timescale.

Capabilities of a mobile extracorporeal membrane oxygenation service for severe respiratory failure delivered by intensive care specialists.

We conducted a single-centre observational study of retrievals for severe respiratory failure over 12 months. Our intensivist-delivered retrieval service has mobile extracorporeal membrane oxygenation capabilities. Sixty patients were analysed: 34 (57%) were female and the mean (SD) age was 44.1 (13.6) years. The mean (SD) PaO2 /FI O2 ratio at referral was 10.2 (4.1) kPa and median (IQR [range]) Murray score was 3.25 (3.0-3.5 [1.5-4.0]). Forty-eight patients (80%) required veno-venous extracorporeal membrane oxygenation at the referring centre. There were no cannulation or extracorporeal membrane oxygenation-related complications. The median (IQR [range]) retrieval distance was 47.2 (14.9-77.0 [2.3-342.0]) miles. There were no major adverse events during retrieval. Thirty-seven patients (77%) who received extracorporeal membrane oxygenation survived to discharge from the intensive care unit and 36 patients (75%) were alive after six months. Senior intensivist-initiated and delivered mobile extracorporeal membrane oxygenation is safe and associated with a high incidence of survival.

Appropriate clinical use of human leukocyte antigen typing for coeliac disease: an Australasian perspective.

The past decade has seen human leukocyte antigen (HLA) typing emerge as a remarkably popular test for the diagnostic work-up of coeliac disease with high patient acceptance. Although limited in its positive predictive value for coeliac disease, the strong disease association with specific HLA genes imparts exceptional negative predictive value to HLA typing, enabling a negative result to exclude coeliac disease confidently. In response to mounting evidence that the clinical use and interpretation of HLA typing often deviates from best practice, this article outlines an evidence-based approach to guide clinically appropriate use of HLA typing, and establishes a reporting template for pathology providers to improve communication of results.

Cognitive impairment in coeliac disease improves on a gluten-free diet and correlates with histological and serological indices of disease severity.

BACKGROUND: Mild impairments of cognition or 'Brain fog' are often reported by patients with coeliac disease but the nature of these impairments has not been systematically investigated. AIM: This longitudinal pilot study investigated relationships between cognitive function and mucosal healing in people with newly diagnosed coeliac disease commencing a gluten-free diet. METHODS: Eleven patients (8 females, 3 males), mean age 30 (range 22-39) years, were tested with a battery of cognitive tests at weeks 0, 12 and 52. Information processing efficacy, memory, visuospatial ability, motoric function and attention were tested. Small bowel biopsies were collected via routine gastroscopy at weeks 12 and 52 and were compared to baseline Marsh scores. Cognitive performance was compared to serum concentrations of tissue transglutaminase antibodies, biopsy outcomes and other biological markers. RESULTS: All patients had excellent adherence to the diet. Marsh scores improved significantly (P = 0.001, Friedman's test) and tissue transglutaminase antibody concentrations decreased from a mean of 58.4 at baseline to 16.8 U/mL at week 52 (P = 0.025). Four of the cognitive tests assessing verbal fluency, attention and motoric function showed significant improvement over the 12 months and strongly correlated with the Marsh scores and tissue transglutaminase antibody levels (r = 0.377-0.735; all P < 0.05). However, no meaningful patterns of correlations were found for nutritional or biochemical markers, or markers of intestinal permeability. CONCLUSIONS: In newly diagnosed coeliac disease, cognitive performance improves with adherence to the gluten-free diet in parallel to mucosal healing. Suboptimal levels of cognition in untreated coeliac disease may affect the performance of everyday tasks.

Nutritional inadequacies of the gluten-free diet in both recently-diagnosed and long-term patients with coeliac disease.

BACKGROUND: Life-long gluten-free diet (GFD) is the only recognised treatment for coeliac disease (CD). The present study aimed to determine the nutritional adequacy of the 'no detectable gluten' diet. METHODS: Seven-day prospective food intake was assessed in 55 patients who were adherent to a GFD for more than 2 years and in 50 newly-diagnosed age- and sex-matched patients (18-71 years, 24% male) studied prospectively over 12 months on GFD. Historical precoeliac intake was also assessed in the latter group. Intake was compared with Australian Nutritional Recommendations and the Australian population data. RESULTS: Nutritional intake was similar between groups. Of macronutrients, only starch intake fell over 12 months (26% to 23%, P = 0.04). Fibre intake was inadequate for all except in diet-experienced men. More than one in 10 of both newly-diagnosed and experienced women had inadequate thiamin, folate, vitamin A, magnesium, calcium and iron intakes. More than one in 10 newly-diagnosed men had inadequate thiamin, folate, magnesium, calcium and zinc intakes. Inadequate intake did not relate to nutrient density of the GFD. Inadequacies of folate, calcium, iron and zinc occurred more frequently than in the Australian population. The frequency of inadequacies was similar pre- and post-diagnosis, except for thiamin and vitamin A, where inadequacies were more common after GFD implementation. CONCLUSIONS: Dietary intake patterns at 12 months on a GFD are similar to longer-term intake. Dietary inadequacies are common and may relate to habitual poor food choices in addition to inherent deficiencies in the GFD. Dietary education should also address the achievement of adequate micronutrient intake. Fortification of GF foods also need to be considered.

Quantification of fructans, galacto-oligosacharides and other short-chain carbohydrates in processed grains and cereals.

BACKGROUND: Wholegrain grains and cereals contain a wide range of potentially protective factors that are relevant to gastrointestinal health. The prebiotics best studied are fructans [fructooligosaccharides (FOS), inulin] and galactooligosaccharides (GOS). These and other short-chain carbohydrates can also be poorly absorbed in the small intestine (named fermentable oligo-, di- and monosaccharides and polyols; FODMAPs) and may have important implications for the health of the gut. METHODS: In the present study, FODMAPs, including fructose in excess of glucose, FOS (nystose, kestose), GOS (raffinose, stachyose) and sugar polyols (sorbitol, mannitol), were quantified using high-performance liquid chromatography with an evaporative light scattering detector. Total fructan was quantified using an enzymic hydrolysis method. RESULTS: Fifty-five commonly consumed grains, breakfast cereals, breads, pulses and biscuits were analysed. Total fructan were the most common short-chain carbohydrate present in cereal grain products and ranged (g per portion as eaten) from 1.12 g in couscous to 0 g in rice; 0.6 g in dark rye bread to 0.07 g in spelt bread; 0.96 g in wheat-free muesli to 0.11 g in oats; and 0.81 g in muesli fruit bar to 0.05 g in potato chips. Raffinose and stachyose were most common in pulses. CONCLUSIONS: Composition tables including FODMAPs and prebiotics (FOS and GOS) that are naturally present in food will greatly assist research aimed at understanding their physiological role in the gut.

Diarrhoea during enteral nutrition is predicted by the poorly absorbed short-chain carbohydrate (FODMAP) content of the formula.

BACKGROUND: Although it is recognized that diarrhoea commonly complicates enteral nutrition, the causes remain unknown. AIM: To identify factors associated with diarrhoea in patients receiving enteral nutrition with specific attention to formula composition. METHODS: Medical histories of in-patients receiving enteral nutrition were identified by ICD-10-AM coding and randomly selected from the year 2003 to 2008. Clinical and demographic data were extracted. Formulas were classified according to osmolality, fibre and FODMAP (fermentable oligo-, di- and mono-saccharides and polyols) content. RESULTS: Formula FODMAP levels ranged from 10.6 to 36.5 g/day. Of 160 patients receiving enteral nutrition, 61% had diarrhoea. Univariate analysis showed diarrhoea was associated with length of stay >21 days (OR 4.2), enteral nutrition duration >11 days (OR 4.0) and antibiotic use (OR 2.1). After adjusting for influencing variables through a logistic regression model, a greater than five-fold reduction in risk of developing diarrhoea was seen in patients initiated on Isosource 1.5 (P = 0.029; estimated OR 0.18). The only characteristic unique to this formula was its FODMAP content, being 47-71% lower than any other formula. CONCLUSIONS: Length of stay and enteral nutrition duration independently predicted diarrhoea development, while being initiated on a lower FODMAP formula reduced the likelihood of diarrhoea. As retrospective evaluation does not support a cause-effect relationship, an interventional study investigating FODMAPs in enteral formula is indicated.

Dietary poorly absorbed, short-chain carbohydrates increase delivery of water and fermentable substrates to the proximal colon.

BACKGROUND: Functional gut symptoms are induced by inclusion and reduced by dietary restriction of poorly absorbed short-chain carbohydrates (FODMAPs), but the mechanisms of action remain untested. AIMS: To determine the effect of dietary FODMAPs on the content of water and fermentable substrates of ileal effluent. METHODS: Twelve ileostomates without evidence of small intestinal disease undertook two 4-day dietary periods, comprising diets differing only in FODMAP content in a randomized, cross-over, single-blinded intervention study. Daytime (14 h) ileal effluent was collected on day four of each diet. Patients rated effluent volume and consistency on a 10-cm visual analogue scale. The FODMAP content of the diet and effluent was measured. RESULTS: Ingested FODMAPs of 32% (range 6-73%) was recovered in the high FODMAP diet effluent. Effluent collection weight increased by a mean of 22% (95% CI, 5-39), water content by 20% (2-38%) and dry weight by 24% (4-43%) with the high compared to low FODMAP diet arm. Output increased by 95 (28-161) mL. Volunteers perceived effluent consistency was thicker (95% CI, 0.6-1.9) with the low FODMAP diet than with the high FODMAP diet (3.5-6.1; P = 0.006). CONCLUSIONS: These data support the hypothetical mechanism; FODMAPs increase delivery of water and fermentable substrates to the proximal colon.

Comparison of the prevalence of fructose and lactose malabsorption across chronic intestinal disorders.

BACKGROUND: Fructose malabsorption, lactose malabsorption and an early rise in breath hydrogen after lactulose (ERBHAL) may play roles in induction of symptoms in gastrointestinal conditions. AIM: To compare prevalence and interactions of fructose malabsorption, lactose malabsorption and ERBHAL among healthy subjects and those with chronic intestinal disorders using consistent breath hydrogen testing methodologies. METHODS: Consecutive series of Caucasian patients with Crohn's disease (n = 91), ulcerative colitis (56), functional gastrointestinal disorders (FGID) (201), coeliac disease (136) and 71 healthy volunteers underwent breath hydrogen testing using lactulose, fructose and lactose. RESULTS: Early rise in breath hydrogen after lactulose occurred more commonly in healthy controls (39%) than in Crohn's disease (20%) and untreated coeliac disease (14%; P < 0.008), but not FGID (27%), ulcerative colitis (26%) or treated coeliac disease (29%). Fructose malabsorption was more frequent in Crohn's disease (61%) than other groups (33-44%, P < 0.05). Lactose malabsorption was most common in Crohn's disease (42%) and ulcerative colitis (40%) and uncommon (10%) in 79 patients with newly diagnosed coeliac disease. In Crohn's disease, concurrent Fructose malabsorption and lactose malabsorption was most common (29%), and the association of fructose malabsorption with ERBHAL seen overall (62%) was not observed (36%, P < 0.0001). CONCLUSIONS: Carbohydrate malabsorption and ERBHAL are normal physiological phenomena. The abnormal patterns observed in Crohn's disease may have pathogenic importance.

Simultaneous detection and quantitation of cytomegalovirus, Epstein-Barr virus, and adenovirus by use of real-time PCR and pooled standards.

Quantitative real-time PCR has become the most widely used preemptive approach for managing cytomegalovirus (CMV), Epstein-Barr virus (EBV), and adenovirus infections in immunosuppressed patients. These three assays are normally available as separate tests, each using five quantitation standards that are tested in duplicate. We have developed an adenovirus-CMV-EBV triplex assay that uses one set of five pooled quantitative standards, tested singly rather than in duplicate. This test demonstrated a sensitivity and an accuracy of quantitation equivalent to those of our previous single tests and was shown to be able to detect mixed infections with no loss in sensitivity. This assay is now in routine use in our laboratory and has considerably simplified the work flow of the laboratory, with a resultant improvement in sample turnaround time and significantly reduced costs.

A new tool for the management of infection in patients with febrile neutropenia.

BACKGROUND: We describe a novel analytical technique for determining instantaneous trends in body temperature data, which may assist clinicians in optimizing antimicrobial therapy in patients with febrile neutropenia. The paper presents a new algorithm, based on a modified second backward difference (M2BD) matrix filter for monitoring temperature response to anti-microbial chemotherapies in neutropenic patients and develops techniques for extracting accurate, instantaneous trend data from clinical time series data. Such an algorithm is needed because it is difficult to assess patient wellbeing in those who are neutropenic. Temperature data, a key indicator of response to antimicrobial therapy, are typically very noisy, with many fluctuations, making it very difficult to identify underlying trends in real time. Clinicians are therefore forced to make important decisions concerning drug therapy on imperfect data. METHODS: In order to determine the underlying temperature trend, analysis of synthetic time series data (with a known underlying trend) was undertaken using both the CUSUM technique and the M2BD matrix filter. The CUSUM analysis was undertaken using four reference temperatures, 37.5 degrees C, 38.0 degrees C, 38.5 degrees C and 39.0 degrees C. A validation study was also undertaken using four sets of noisy synthetic temperature data to evaluate the performance of the M2BD filter. The M2BD filter was then used to analyse anonymized serial temperature data from a neutropenic patient undergoing chemotherapy. RESULTS: For all four reference temperatures the CUSUM analysis failed to predict the underlying temperature trend. By comparison, the M2BD filter extracted, in real time, the underlying temperature trend with great accuracy and no time lag. In the validation study, the M2BD filter accurately extracted the underlying temperature trend for all four of the synthetic datasets. With regard to the anonymized patient data, the M2BD filter again performed well, accurately determining the underlying trend. CONCLUSION: The study demonstrated that the M2BD filter is capable of instantaneously extracting underlying trends from clinical time series data. This finding suggests that this algorithm has great potential as a tool for assisting clinicians in the management of patients with febrile neutropenia.

Amino acid partitioning using a Fiedler vector model.

This paper presents a new Fiedler vector model for categorising amino acids, which is based on the Miyazawa-Jernigan matrix. The model splits the amino acid residues into two hydrophobic groups (LFI) and (MVWCY) and two polar groups (HATGP) and (RQSNEDK). In so doing, it independently confirms the findings of Wang and Wang and Cieplak et al. and demonstrates the validity of using eigenvectors to partition amino acid groups.

Review article: fructose malabsorption and the bigger picture.

Fructose is found widely in the diet as a free hexose, as the disaccharide, sucrose and in a polymerized form (fructans). Free fructose has limited absorption in the small intestine, with up to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine. The physiological consequences of their malabsorption include increasing osmotic load, providing substrate for rapid bacterial fermentation, changing gastrointestinal motility, promoting mucosal biofilm and altering the profile of bacteria. These effects are additive with other short-chain poorly absorbed carbohydrates such as sorbitol. The clinical significance of these events depends upon the response of the bowel to such changes; they have a higher chance of inducing symptoms in patients with functional gut disorders than asymptomatic subjects. Restricting dietary intake of free fructose and/or fructans may have durable symptomatic benefits in a high proportion of patients with functional gut disorders, but high quality evidence is lacking. It is proposed that confusion over the clinical relevance of fructose malabsorption may be reduced by regarding it not as an abnormality but as a physiological process offering an opportunity to improve functional gastrointestinal symptoms by dietary change.

Personal view: food for thought--western lifestyle and susceptibility to Crohn's disease. The FODMAP hypothesis.

Susceptibility to the development of Crohn's disease involves a combination of genetic and environmental factors. The association of Crohn's disease with westernization has implicated lifestyle factors in pathogenesis. While diet is a likely candidate, evidence for specific changes in dietary habits and/or intake has been lacking. A new hypothesis is proposed, by which excessive delivery of highly fermentable but poorly absorbed short-chain carbohydrates and polyols (designated FODMAPs--Fermentable Oligo-, Di- and Mono-saccharides And Polyols) to the distal small intestinal and colonic lumen is a dietary factor underlying susceptibility to Crohn's disease. The subsequent rapid fermentation of FODMAPs in the distal small and proximal large intestine induces conditions in the bowel that lead to increased intestinal permeability, a predisposing factor to the development of Crohn's disease. Evidence supporting this hypothesis includes the increasing intake of FODMAPs in western societies, the association of increased intake of sugars in the development of Crohn's disease, and the previously documented effects of the ingestion of excessive FODMAPs on the bowel. This hypothesis provides potential for the design of preventive strategies and raises concern about current enthusiasm for putative health-promoting effects of FODMAPs. One of the greatest challenges in defining the pathogenesis of Crohn's disease is to identify predisposing environmental factors. Such an achievement might lead to the development of preventive strategies for, and the definition of, possible target for changing the natural history of this serious disease. The present paper describes a new hypothesis for one such environmental factor.