Ischaemic stroke caused by Group B Streptococcus associated meningoencephalitis in young, immunocompetent adults - a case series and systematic review of literature.

A 51-year-old man presented with mild headache followed by sudden onset of right sided weakness and dysarthria on the background of one week history of right sided sciatica and malaise. He was apparently immunocompetent with only past medical history being hypertension. There was no consumption of tobacco or excess alcohol and he previously had normal liver and renal function.

Avian agnosia: A window into auditory semantics.

The functional and neural organisation of auditory knowledge is relatively poorly understood. The breakdown of conceptual knowledge in semantic dementia has revealed that pre-morbid expertise influences the extent to which knowledge is differentiated. Whether this principle applies to a similar extent in the auditory domain is not yet known. Previous reports of patients with impaired auditory vs. intact visual expert knowledge suggest that expertise may have differential effects upon the organisation of auditory and visual knowledge. An equally plausible alternative, however, is that auditory knowledge is simply more vulnerable to deterioration. Thus, expertise effects in the auditory domain may not yet have been observed because knowledge of auditory expert vs. non-expert knowledge has yet to be compared. We had the opportunity to address this issue by studying SA, a patient with semantic dementia and extensive pre-morbid knowledge of birds. We undertook a systematic investigation of SA's auditory vs. visual knowledge from matched expert vs. non-expert categories. Relative to a group of 10 age, education and IQ matched bird experts, SA showed impaired auditory vs. intact visual avian knowledge, despite intact basic auditory perceptual abilities. This was explained by independent effects of modality and expertise. Thus, he was also disproportionately impaired for auditory vs. visual knowledge of items from non-expert categories. In both auditory and visual modalities, his performance was relatively more impaired on tests of non-expert vs. expert knowledge. These findings suggest that, while auditory knowledge may be more vulnerable to deterioration, expertise modulates visual and auditory knowledge to a similar extent.

Antibiotic-loaded bone void filler accelerates healing in a femoral condylar rat model.

AIMS: Demineralised bone matrix (DBM) is rarely used for the local delivery of prophylactic antibiotics. Our aim, in this study, was to show that a graft with a bioactive glass and DBM combination, which is currently available for clinical use, can be loaded with tobramycin and release levels of antibiotic greater than the minimum inhibitory concentration for Staphylococcus aureus without interfering with the bone healing properties of the graft, thus protecting the graft and surrounding tissues from infection. MATERIALS AND METHODS: Antibiotic was loaded into a graft and subsequently evaluated for drug elution kinetics and the inhibition of bacterial growth. A rat femoral condylar plug model was used to determine the effect of the graft, loaded with antibiotic, on bone healing. RESULTS: We found that tobramycin loaded into a graft composed of bioglass and DBM eluted antibiotic above the minimum inhibitory concentration for three days in vitro. It was also found that the antibiotic loaded into the graft produced no adverse effects on the bone healing properties of the DBM at a lower level of antibiotic. CONCLUSION: This antibiotic-loaded bone void filler may represent a promising option for the delivery of local antibiotics in orthopaedic surgery. Cite this article: Bone Joint J 2016;98-B:1126-31.

Making EBSD on water ice routine.

Electron backscatter diffraction (EBSD) on ice is a decade old. We have built upon previous work to select and develop methods of sample preparation and analysis that give >90% success rate in obtaining high-quality EBSD maps, for the whole surface area (potentially) of low porosity (<15%) water ice samples, including very fine-grained (<10 µm) and very large (up to 70 mm by 30 mm) samples. We present and explain two new methods of removing frost and providing a damage-free surface for EBSD: pressure cycle sublimation and 'ironing'. In general, the pressure cycle sublimation method is preferred as it is easier, faster and does not generate significant artefacts. We measure the thermal effects of sample preparation, transfer and storage procedures and model the likelihood of these modifying sample microstructures. We show results from laboratory ice samples, with a wide range of microstructures, to illustrate effectiveness and limitations of EBSD on ice and its potential applications. The methods we present can be implemented, with a modest investment, on any scanning electron microscope system with EBSD, a cryostage and a variable pressure capability.

Magnetic Nanoparticles with High Specific Absorption Rate at Low Alternating Magnetic Field.

This paper describes the synthesis and properties of a new type of magnetic nanoparticle (MNP) for use in the hyperthermia treatment of tumors. These particles consist of 2-4 nm crystals of gamma-Fe2O3 gathered in 20-40 nm aggregates with a coating of carboxymethyl-dextran, producing a zetasize of 110-120 nm. Despite their very low saturation magnetization (1.5-6.5 emu/g), the specific absorption rate (SAR) of the nanoparticles is 22-200 W/g at applied alternating magnetic field (AMF) with strengths of 100-500 Oe at a frequency of 160 kHz.

Clinical relevance of a positive molecular test in the diagnosis of Clostridium difficile infection.

BACKGROUND: In 2011, the Department of Health advised that a two-stage test approach should be used to improve accuracy of Clostridium difficile infection (CDI) diagnosis. No specific test protocol was established at that time. AIM: To compare clinical features of inpatient CDI cases identified by toxin enzyme immunoassay (EIA) with those identified as polymerase chain reaction (PCR) positive but toxin EIA negative. METHODS: During a six-month period (2011-2012), 2181 liquid faeces samples submitted to North Bristol NHS Trust were tested by EIA for both toxin and glutamate dehydrogenase (GDH). A total of 215 toxin or GDH EIA-positive samples were tested by Cepheid Xpert PCR assay; 128 clinically evaluable inpatients were grouped by test result, and their duration of diarrhoea and 14-day mortality compared. FINDINGS: Inpatients with a positive PCR but negative toxin EIA had a significantly lower 14-day all-cause mortality [11%; 95% confidence interval (CI): 4-23%] than patients with a positive PCR and positive toxin EIA test (37%; 95% CI: 19-59%; P = 0.01), and a smaller proportion of patients had prolonged diarrhoea (>5 days or unresolved at death: 19%; CI: 9-32%, vs 67%; CI: 45-84%; P < 0.001). A positive toxin EIA test was a significant independent predictor of death [odds ratio (OR): 4.7, 95% CI: 1.4-15.4; P = 0.01] and prolonged diarrhoea (OR: 8.6; CI: 2.9-25.6; P < 0.001), but a positive PCR (given positive GDH EIA) was not. CONCLUSION: The clinical significance of a positive PCR result without a positive toxin EIA is questionable; such a result is associated with a significantly lower mortality and shorter duration of symptoms than patients with a positive toxin EIA.

Dislocations in nanostructured two-phase Fe30Ni20Mn20Al30.

In a previous study, the dislocations in Fe(30)Ni(20)Mn(25)Al(25) (at. %), which consist of 50 nm wide alternating b.c.c. and B2 phases, were shown to have a/2<111> Burgers vectors after room temperature deformation. The dislocations were found to glide in pairs on both {110} and {112} slip planes and were relatively widely separated in the b.c.c. phase, where the dislocations were uncoupled, and closely spaced in the B2 phase, where the dislocations were connected by an anti-phase boundary. In this article, we analyze the dislocations in the two ~5 nm-wide B2 phases in a related two-phase alloy Fe(30)Ni(20)Mn(20)Al(30), with compositions Fe-23Ni-21Mn-24Al and Fe-39Ni-12Mn-34Al, compressed to ~3% strain at a strain rate 5 × 10(-4) s(-1) at 873 K (the lowest temperature at which substantial plastic flow was observed). It is shown that slip occursby the glide of a<100> dislocations. A review of the literature suggests that the differences in the observed slip vector between these B2 phases could be due to the differences in composition, differences in deformation temperature, or possibly both.

The management of diabetes in terminal illness related to cancer.

The management of diabetes during terminal illness is complex, with lack of agreement and consensus among physicians and multidisciplinary teams. Despite the plethora of guidelines available for the management of diabetes, there exists no agreed, evidence-based strategy for managing diabetes during terminal illness and at the end of life. A number of physiological factors may influence glycaemic control during terminal illness. These include anorexia, cachexia, malabsorption, renal and hepatic failure. Furthermore, controversy exists on the frequency of blood glucose monitoring, the optimum blood glucose range and how to achieve this. We review the factors influencing blood glucose during terminal illness and provide a suggested approach to managing patients with type 1 and type 2 diabetes during the early and late stages of terminal illness.

Associations between types of dietary fat and fish intake and risk of stroke in the Caerphilly Prospective Study (CaPS).

BACKGROUND: Few population-based longitudinal studies on diet and stroke have been conducted, and associations between dietary fat and fish intake and risk of stroke are unclear. OBJECTIVES: To prospectively examine relationships between intakes of total fat, saturated fat, unsaturated fat, white fish and oily fish and risk of stroke in a well-defined population of 2710 middle-aged men. STUDY DESIGN: Prospective cohort study. METHODS: Detailed information on health and lifestyle factors was collected via interview, and diet was assessed on three occasions using a food frequency questionnaire. Stroke ascertainment was by self-report and inspection of clinical records. Extracted data were assessed by two independent experts. RESULTS: During a median follow-up of 18 years, 225 strokes (209 ischaemic and 19 haemorrhagic) were eligible for inclusion in the analyses. For most recent diet (i.e. food frequency questionnaire data collected immediately prior to the stroke event), there was a slightly lower risk of stroke with higher intakes of unsaturated fat and oily fish. Multiple adjusted hazard ratios (HRs) for the lowest vs highest quintiles of unsaturated fat and oily fish intakes were 0.66 [95% confidence interval (CI) 0.41-1.05, P trend = 0.13] and 0.66 (95% CI 0.41-1.05, P trend = 0.09), respectively. Baseline and cumulative diets showed a slightly higher risk of stroke with higher intake of white fish; HRs for the lowest vs highest quintiles were 1.16 (95% CI 0.76-1.77, P trend = 0.22) and 1.28 (95% CI 0.77-2.13, P trend = 0.48), respectively. CONCLUSIONS: Overall, strong associations were not found between intakes of different types of fat and fish and risk of stroke in middle-aged men. The inverse associations between unsaturated fat and oily fish intakes and risk of stroke were weak, but the direction of association was broadly consistent with other studies; however, these relatively weak associations were not conventionally statistically significant.

Herd management practices and the transmission of Johne's disease within infected dairy herds in Victoria, Australia.

A retrospective cohort study involving 137 dairy herds randomly selected from all 390 participating in the Victorian Test and Control Program for bovine Johne's disease was undertaken to gain insight into the relationships between calf rearing practices and the occurrence of bovine Johne's disease on infected dairy farms. Each study farm was visited between July 2005 and January 2006 and a structured survey examining herd management and calf rearing practices was completed. The resultant data, along with information from annual herd testing for Johne's disease and records of clinical Johne's disease diagnosed in the herd, from May 1990 to March 2008, were analysed. Factors associated with time to the birth of the animal that was the first home-bred clinical case of Johne's disease or ELISA positive animal born after the second annual whole herd test in the herd were investigated using survival analysis methods. The publicly-subsidised Test and Control Program commenced in 1996. On the 1st of July 2003 the program was modified with more rigorous and externally audited calf rearing requirements introduced for all participants. The more stringent calf rearing requirements introduced in July 2003 appear to have translated into significantly reduced disease transmission within the infected study herds.

Factors that influence decisions about cardiopulmonary resuscitation: the views of doctors and medical students.

BACKGROUND: A number of studies have explored doctors' views and experiences of cardiopulmonary resuscitation (CPR), but to our knowledge there has been no research to identify the information that doctors take into account when they make decisions about CPR. PURPOSE OF STUDY: To investigate factors that influence decisions about CPR. STUDY DESIGN: Qualitative study involving six focus groups with 17 doctors and four medical students in Leicester, UK. RESULTS: Doctors and medical students considered a number of factors important when making decisions about CPR-namely, the patient's diagnosis, prognosis, age, quality of life, the opinions of doctors and other medical staff, and the wishes of patients and relevant others. The relative importance of each of these factors varied significantly and was influenced by the doctors' own beliefs and values. CONCLUSIONS: Doctors would benefit from greater support for their decision making in relation to resuscitation to reduce variability in clinical practice and to promote appropriate patient care. Identification of factors that influence doctors' individual beliefs, attitudes and values towards resuscitation and improvement in the quality of patient communication may help to guide policy in this area.

Photosynthetic control of atmospheric carbonyl sulfide during the growing season.

Climate models incorporate photosynthesis-climate feedbacks, yet we lack robust tools for large-scale assessments of these processes. Recent work suggests that carbonyl sulfide (COS), a trace gas consumed by plants, could provide a valuable constraint on photosynthesis. Here we analyze airborne observations of COS and carbon dioxide concentrations during the growing season over North America with a three-dimensional atmospheric transport model. We successfully modeled the persistent vertical drawdown of atmospheric COS using the quantitative relation between COS and photosynthesis that has been measured in plant chamber experiments. Furthermore, this drawdown is driven by plant uptake rather than other continental and oceanic fluxes in the model. These results provide quantitative evidence that COS gradients in the continental growing season may have broad use as a measurement-based photosynthesis tracer.

Microbial investigation of venous leg ulcers.

OBJECTIVE: To investigate microbiology laboratory reporting policies, whether practitioners working in primary care adhered to the relevant guidelines when submitting swabs from venous leg ulcers (VLUs), and the impact of laboratory reports on antibiotic usage forVLUs. METHOD: Questionnaires were sent to all microbiology laboratories in England and Wales, and to clinicians who had submitted VLU swabs to one laboratory. RESULTS: Ninety-five (47%) laboratories responded. Laboratories processed a mean of 7.3 leg ulcer swabs/100,000 population/week but were often unable to identify the leg ulcer aetiology from the clinical details provided. All laboratories stated that they routinely reported group A haemolytic streptococci and meticillin-sensitive and resistant Staphylococcus aureus; 75% always reported antibiotic susceptibility for these isolates. The majority reported other beta-haemolytic streptococci. A total of 126 clinicians (64%) returned their questionnaires; 100 had confirmed in their swab submission that the ulcer was of venous aetiology and so were included in the analysis. Eighty per cent of the swabs were submitted in accordance with guidelines, with increased pain (61%) being the most common reason. Discharge/exudate (52%) and malodour (41%) were common reasons for swab submissions, even though the guidelines do not cite them as clinical signs of infection. Reporting of antibiotic susceptibilities was associated with increased antibiotic usage. CONCLUSION: Clinicians in primary care generally adhere to guidelines when submittingVLU specimens for microbiological investigation. Clinicians need to include clinical information with the swab so that laboratories can interpret the microbiology results. To reduce the use of antibiotics in the management ofVLUs, laboratories need to be selective in their organism and antibiotic-susceptibility reporting.

Dislocation identification and in situ straining in the spinodal Fe30Ni20Mn25Al25 alloy.

Dislocations in the spinodal alloy Fe(30)Ni(20)Mn(25)Al(25), which is composed of alternating BCC and B2 (ordered BCC) phases, have been investigated using weak-beam transmission electron microscopy (TEM). The alloy was compressed at room temperature in an as-hot-extruded state to strains of approximately 3% for post-mortem dislocation analysis. Dislocations with a/2<111> Burgers vectors were found to glide in pairs on both {110} and {112} slip planes. TEM in situ straining experiments were also performed on both the as-extruded alloy and an arc-melted alloy. The in situ straining observations confirmed that dislocations were able to pass between both spinodal phases. Partial dislocation separations were relatively wide in the BCC phase and narrow in the B2 phase. Dislocation glide, as opposed to twinning (both of which have been observed in other BCC-based spinodals), was also found to be the only room temperature deformation mechanism.

Ethnic differences in healthcare-seeking behaviour and management for acute chest pain: secondary analysis of the MINAP dataset 2002-2003.

OBJECTIVE: To examine whether there are ethnic differences in the healthcare-seeking behaviour and management of patients with chest pain. DESIGN: Prospective cohort of patients attending accident and emergency departments with chest pain. SETTING: Hospitals in England and Wales from 1 January 2002 to 31 December 2003. PARTICIPANTS: Patients with chest pain. MAIN OUTCOME MEASURES: Whether patients arrived by ambulance, whether they received thrombolysis and the time it took from symptom onset to arrive at hospital and receive thrombolysis. RESULTS: South Asian patients were less likely to arrive by ambulance (age and sex adjusted odds ratio 0.64, 95% CI 0.60 to 0.69, p<0.001) regardless of admission diagnosis. Overall, they were more likely to receive thrombolysis (adjusted multivariable odds ratio 1.19, 95% CI 1.10 to 1.30, p<0.001) and the difference was more marked if they had non-specific ECG changes for heart disease rather than definite evidence of a myocardial infarction. There was no evidence of an important clinical delay in South Asians receiving thrombolysis after arrival at hospital. CONCLUSIONS: There are ethnic differences in healthcare-seeking behaviour and the way doctors manage South Asians with chest pain. The relative underuse of ambulances by South Asians may either reflect cultural differences or geographical proximity to hospitals. Doctors may have a lower threshold for giving thrombolytic therapy to South Asian men with chest pain possibly because they are aware of the increased risk of coronary heart disease in this population.

Long term survival in a patient with variant Creutzfeldt-Jakob disease treated with intraventricular pentosan polysulphate.

Variant Creutzfeldt-Jakob disease (vCJD) is a neurodegenerative disease that principally affects young people and has a median duration of illness of 13 (range 6-39) months. vCJD is incurable and there are currently no treatments that conclusively slow the rate of disease progression. However, recent animal studies and isolated case reports have suggested that treatment with intraventricular pentosan polysulphate (PPS) may be beneficial in the treatment of patients with vCJD. We report a case of a 22-year-old male with vCJD treated 19 months after the onset of clinical symptoms with continuous intraventricular PPS (32 microg/kg/day) over a period of 31 months. Treatment with PPS appeared to be safe and well tolerated and was associated with prolonged survival (51 months) when compared to natural history studies. However, PPS treatment did not appear to arrest the progression of the disease.

Synthesis and heating effect of iron/iron oxide composite and iron oxide nanoparticles.

Fe/Fe oxide nanoparticles, in which the core consists of metallic Fe and the shell is composed of Fe oxides, were obtained by reduction of an aqueous solution of FeCl3 within a NaBH4 solution, or, using a water-in-oil micro-emulsion with CTAB as the surfactant. The reduction was performed either in an inert atmosphere or in air, and passivation with air was performed to produce the Fe/Fe3O4 core/shell composite. Phase identification and particle size were determined by X-ray diffraction and TEM. Thermal analysis was performed using a differential scanning calorimeter. The quasistatic magnetic properties were measured using a VSM, and the specific absorption rates (SARs) of both Fe oxide and Fe/Fe3O4 composite nanoparticles either dispersed in methanol or in an epoxy resin were measured by Luxtron fiber temperature sensors in an alternating magnetic field of 150 Oe at 250 kHz. It was found that the preparation conditions, including the concentrations of solutions, the mixing procedure and the heat treatment, influence the particle size, the crystal structure and consequently the magnetic properties of the particles. Compared with Fe oxides, the saturation magnetization (MS ) of Fe/Fe3O4 particles (100-190 emu/g) can be twice as high, and the coercivity (HC ) can be tunable from several Oe to several hundred Oe. Hence, the SAR of Fe/Fe3O4 composite nanoparticles can be much higher than that of Fe oxides, with a maximum SAR of 345 W/g. The heating behavior is related to the magnetic behavior of the nanoparticles.

Intratumoral Iron Oxide Nanoparticle Hyperthermia and Radiation Cancer Treatment.

The potential synergism and benefit of combined hyperthermia and radiation for cancer treatment is well established, but has yet to be optimized clinically. Specifically, the delivery of heat via external arrays /applicators or interstitial antennas has not demonstrated the spatial precision or specificity necessary to achieve appropriate a highly positive therapeutic ratio. Recently, antibody directed and possibly even non-antibody directed iron oxide nanoparticle hyperthermia has shown significant promise as a tumor treatment modality. Our studies are designed to determine the effects (safety and efficacy) of iron oxide nanoparticle hyperthermia and external beam radiation in a murine breast cancer model. METHODS: MTG-B murine breast cancer cells (1 × 106) were implanted subcutaneous in 7 week-old female C3H/HeJ mice and grown to a treatment size of 150 mm3 +/- 50 mm3. Tumors were then injected locally with iron oxide nanoparticles and heated via an alternating magnetic field (AMF) generator operated at approximately 160 kHz and 400 - 550 Oe. Tumor growth was monitored daily using standard 3-D caliper measurement technique and formula. specific Mouse tumors were heated using a cooled, 36 mm diameter square copper tube induction coil which provided optimal heating in a 1 cm wide region in the center of the coil. Double dextran coated 80 nm iron oxide nanoparticles (Triton Biosystems) were used in all studies. Intra-tumor, peri-tumor and rectal (core body) temperatures were continually measured throughout the treatment period. RESULTS: Preliminary in vivo nanoparticle-AMF hyperthermia (167 KHz and 400 or 550 Oe) studies demonstrated dose responsive cytotoxicity which enhanced the effects of external beam radiation. AMF associated eddy currents resulted in nonspecific temperature increases in exposed tissues which did not contain nanoparticles, however these effects were minor and not injurious to the mice. These studies also suggest that iron oxide nanoparticle hyperthermia is more effective than nonnanoparticle tumor heating techniques when similar thermal doses are applied. Initial electron and light microscopy studies of iron oxide nanoparticle and AMF exposed tumor cells show a rapid uptake of particles and acute cytotoxicity following AMF exposure.

Meta-analysis of vitamin D receptor polymorphisms and pulmonary tuberculosis risk.

Several case-control studies performed in populations where the incidence of tuberculosis (TB) is high have examined genetic susceptibility to TB. The Vitamin D receptor (VDR) gene is a good candidate, because it influences immune response, and associations between TaqI and FokI polymorphisms in the VDR gene and pulmonary TB risk have been found. Furthermore, if a relationship between these polymorphisms and TB risk is confirmed this will be important evidence pointing to vitamin D as a potential preventive agent for TB. We carried out a systematic review and meta-analysis, and found that results were inconclusive and studies were underpowered.

Effect of compliance with recommended calf-rearing practices on control of bovine Johne's disease.

OBJECTIVE: To assess the degree of compliance with recommended management procedures for the control of bovine Johne's disease and study the relationship between aspects of calf management and testing/disease outcomes in the herds. PROCEDURE: Fifty-four south Gippsland dairy herds participating in the Victorian bovine Johne's disease test and control program were visited between July and November 2002 and an audit of calf rearing practices was conducted. The results of testing completed under the program were analysed for each of the herds. Twenty seven management factors were examined for a relationship with the presence of clinical cases of Johne's disease or cattle with positive ELISA test results that were born after the completion of the second whole herd test. Logistic regression was used to examine the strength of relationships between the management practices and the frequency with which new cases of Johne's disease arose. RESULTS AND CONCULSIONS: Calves were removed from their dams within 12 hours of birth in only 17 (31.5%) of the herds. However, in all but one herd the calves were removed within 24 hours of birth. In 42 herds (77.8%) calf rearing facilities were adequately separated from adult cattle and the faeces from adult cattle. In 41 herds (75.9%) calves up to the age of 12 months were grazed on paddocks that were free of manure or effluent from adult cattle. However, in only 10 (18.5%) of the herds were all three of these calf management practices applied. Feeding whole milk containing antibiotic residues, or providing water for calves from birth, were found to have statistically significant associations with an increased occurrence of cases of bovine Johne's disease in the study herds. The practice of allowing cows to calve in a paddock was found to be associated with reduced occurrence of bovine Johne's disease. These associations were still found after analysis that included herd size, the number of clinical cases that had occurred in the herds before the start of testing, the number of animals with positive ELISA tests that were detected at the first test and the number of years of participation in the test and cull program. Early separation of newborn calves from cows and grazing calves under 12 months of age in areas free of adult cattle were not found to be protective against Johne's disease.