Cardiorespiratory fitness and accelerometer-determined physical activity following one year of free-living high-intensity interval training and moderate-intensity continuous training: a randomized trial.

BACKGROUND: Free-living adherence to high-intensity interval training (HIIT) has not been adequately tested. This randomized trial examined changes in cardiorespiratory fitness (CRF) and accelerometer-measured purposeful physical activity over 12 months of free-living HIIT versus moderate-intensity continuous training (MICT). METHODS: Ninety-nine previously low-active participants with overweight/obesity were randomly assigned to HIIT (n = 47) or MICT (n = 52). Both interventions were combined with evidence-based behaviour change counselling consisting of 7 sessions over 2 weeks. Individuals in HIIT were prescribed 10 X 1-min interval-based exercise 3 times per week (totalling 75 min) whereas individuals in MICT were prescribed 150 min of steady-state exercise per week (50 mins 3 times per week). Using a maximal cycling test to exhaustion with expired gas analyses, CRF was assessed at baseline and after 6 and 12 months of free-living exercise. Moderate-to-vigorous physical activity of 10+ minutes (MVPA10+) was assessed by 7-day accelerometry at baseline, 3, 6, 9, and 12 months. Intention to treat analyses were conducted using linear mixed models. RESULTS: CRF was improved over the 12 months relative to baseline in both HIIT (+ 0.15 l/min, 95% CI 0.08 to 0.23) and MICT (+ 0.11 l/min, 95% CI 0.05 to 0.18). Both groups improved 12-month MVPA10+ above baseline (HIIT: + 36 min/week, 95% CI 17 to 54; MICT: + 69 min/week, 95% CI 49 to 89) with the increase being greater (by 33 min, 95% CI 6 to 60) in MICT (between group difference, P = 0.018). CONCLUSION: Despite being prescribed twice as many minutes of exercise and accumulating significantly more purposeful exercise, CRF improvements were similar across 12 months of free-living HIIT and MICT in previously low-active individuals with overweight/obesity.

The development of a theory informed behaviour change intervention to improve adherence to dietary and physical activity treatment guidelines in individuals with familial hypercholesterolaemia (FH).

BACKGROUND: Familial hypercholesterolaemia (FH) is a genetic condition characterised by elevated levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of cardiovascular disease (CVD). Following dietary and physical activity guidelines could help minimise this risk but adherence is low. Interventions to target these behaviours are therefore required. A comprehensive understanding of the target behaviours and behaviour change theory should drive the process of intervention development to increase intervention effectiveness and scalability. This paper describes the application of a theoretical framework to the findings of a qualitative evidence synthesis (QES) to inform the content and delivery of an intervention to improve adherence to dietary and physical activity guidelines in individuals with FH. METHODS: The Behaviour Change Wheel (BCW) was used to guide intervention development. Factors influencing dietary and physical activity behaviours were identified from an earlier QES and mapped onto factors within the BCW. A comprehensive behavioural diagnosis of these factors was conducted through application of the theoretical domains framework (TDF). Using these data, the most appropriate intervention functions and behaviour change techniques (BCTs) for inclusion in the intervention were identified. Decision making was guided by evaluation criteria recommended by BCW guidance and feedback from individuals with FH. RESULTS: Factors influencing dietary and physical activity behaviours mapped onto twelve of the fourteen TDF domains, with seven intervention functions deemed suitable to target the domains' theoretical constructs. Twenty-six BCTs were identified as being appropriate for delivery within these functions and were included in the intervention. For instance, within the enablement intervention function, the BCT problem solving was incorporated by inclusion of a 'barriers and solutions' section. Guided by evaluation criteria and feedback from individuals with FH, the intervention will be delivered as an hour-long family-based appointment, followed up with four telephone calls. CONCLUSIONS: The novel application of the BCW and TDF to the results of a QES has enabled the development of a theory and evidence informed behaviour change intervention. This systematic approach facilitates evaluation of the intervention as part of an ongoing feasibility trial. The transparent approach taken can be used to guide intervention development by researchers in other fields.

Successful embolisation of pelvic fistulating vessels to the prostate arising after TURP - a rare cause of postoperative bleeding.

Transurethral resection of the prostate (TURP) is considered the gold-standard operation to treat lower urinary tract symptoms due to benign prostatic enlargement in men. Postoperative bleeding is a recognised complication and managing it is a core skill required by attending urologists. We report a rare case of postoperative bleeding caused by fistulating vessels to the prostate which developed after TURP. These fistulas arose from the right internal iliac vessels and communicated with pre-existing pelvic varices affecting the right paraprostaticand seminal vesicle tissues. The fistulating vessels were successfully embolised with liquid embolic agent. Surgeons should be aware that persisting haemorrhage can occur post-TURP from the rare presence of fistulating vessels communicating with pelvic varices. Early computed tomography angiographic assessment is warranted in cases where bleeding is prolonged and refractory to standard management in view of timely referral for percutaneous embolisation.

Don't go chasing artificial waterfalls: Artificial line limits and cascading failures in power grids.

Research on cascading failures in power-transmission networks requires detailed data on the capacity of individual transmission lines. However, these data are often unavailable to researchers. Consequently, line limits are often modeled by assuming that they are proportional to some average load. However, there is scarce research to support this assumption as being realistic. In this paper, we analyze the proportional loading (PL) approach and compare it to two linear models that use voltage and initial power flow as variables and are trained on the line limits of a real power network that we have access to. We compare these artificial line-limit methods using four tests: the ability to model true line limits, the damage done during an attack, the order in which edges are lost, and accuracy ranking the relative performance of different attack strategies. We find that the linear models are the top-performing method or are close to the top in all the tests we perform. In comparison, the tolerance value that produces the best PL limits changes depending on the test. The PL approach was a particularly poor fit when the line tolerance was less than two, which is the most commonly used value range in cascading failure research. We also find indications that the accuracy of modeling line limits does not indicate how well a model will represent grid collapse. The findings of this paper provide an understanding of the weaknesses of the PL approach and offer an alternative method of line-limit modeling.

The temporal profile of retinal cell genesis in the marmoset monkey.

The New World marmoset monkey (Callithrix jacchus) has a relatively short gestational period compared with other primates but possesses a retina at a similar stage of maturation by birth. Previous studies have highlighted that the complex fovea of the marmoset undergoes a more rapid postnatal development in comparison with the Macaca monkey, reaching a mature stage earlier than these species. In this current study, we examined the prenatal proliferation profile of cells in the entire retina employing the thymidine analogs and also determined their phenotype by double-label immunocytochemistry using type-specific markers. Akin to other primate species, we demonstrate a centroperipheral gradient in the emergence of both neurons and Müller glia with cones, ganglion cells, and horizontal cells generated first in the fovea at fetal day (Fd)70-74 and with the last generated at the retinal edge at Fd115. Rods, bipolar cells, amacrine cells, displaced amacrine cells, and Müller glia were generated between Fd76 and Fd135 along the same gradient. Similar to foveal development, marmoset neuronal generation was rapid, only taking 51% of gestation whereas in Macaca this takes 81%.

Protocolised approach to end-of-life care in the ICU--the ICU PALCare Pilot Project.

International literature on end-of-life care in intensive care units (ICUs) supports the use of 'protocol bundles', which is not common practice in our 18-bed adult general ICU in Sydney, New South Wales. We conducted a prospective observational study to identify problems related to end-of-life care practices and to determine whether there was a need to develop protocol bundles. Any ICU patient who had 'withdrawal' of life-sustaining treatment to facilitate a comfortable death was eligible. Exclusion criteria included organ donors, unsuitable family dynamics and lack of availability of research staff to obtain family consent. Process-of-care measures were collected using a standardised form. Satisfaction ratings were obtained using de-identified questionnaire surveys given to the healthcare staff shortly after the withdrawal of therapy and to the families 30 days later. Twenty-three patients were enrolled between June 2011 and July 2012. Survey questionnaires were given to 25 family members and 30 healthcare staff, with a high completion rate (24 family members [96%] and 28 staff [93.3%]). Problems identified included poor documentation of family meetings (39%) and symptom management. Emotional/spiritual support was not offered to families (39.1%) or ICU staff (0%). The overall level of end-of-life care was good. The overwhelming majority of families and healthcare staff were highly satisfied with the care provided. Problems identified related to communication documentation and lack of spiritual/emotional support. To address these problems, targeted measures would be more useful than the adoption of protocol bundles. Alternate models of satisfaction surveys may be needed.

Retrograde transneuronal degeneration in the retina and lateral geniculate nucleus of the V1-lesioned marmoset monkey.

Retrograde transneuronal degeneration (RTD) of retinal ganglion cells and dorsal lateral geniculate (LGN) neurons are well described following a lesion of the primary visual cortex (V1) in both Old World monkeys and humans. Based on previous studies of New World monkeys and prosimians, it was suggested that these species displayed no RTD following a lesion of V1. In this study of the New World marmoset monkey, 1 year after a unilateral V1 lesion either in adults or at 14 days after birth, we observed ~20 % ganglion cell (GC) loss in adult but ~70 % in infants. This finding is similar to the RTD previously described for Old World Macaca monkeys. Furthermore, in infants we find a similar amount of RTD at 3 weeks and 1 year following lesion, demonstrating that RTD is very rapid in neonates. This highlights the importance of trying to prevent the rapid onset of RTD following a lesion of V1 in early life as a strategy for improved functional recovery. Despite differences in GC loss, there was little difference between LGN degeneration in infant versus adult lesions. A wedge on the horizontal meridian corresponding to the LGN foveal representation revealed extensive neuronal loss. Retinal afferent input was labeled by cholera toxin B subunit. Input to the degenerated parvocellular layers was difficult to detect, while input to magnocellular and koniocellular layers was reduced but still apparent. Our demonstration that the New World marmoset monkey shares many of the features of neuroplasticity with Old World Macaca monkeys and humans emphasizes the opportunity and benefit of marmosets as models of visual cortical injury.

Donor-recipient size mismatch in paediatric renal transplantation.

Introduction. End stage renal failure in children is a rare but devastating condition, and kidney transplantation remains the only permanent treatment option. The aim of this review was to elucidate the broad surgical issues surrounding the mismatch in size of adult kidney donors to their paediatric recipients. Methods. A comprehensive literature search was undertaken on PubMed, MEDLINE, and Google Scholar for all relevant scientific articles published to date in English language. Manual search of the bibliographies was also performed to supplement the original search. Results. Size-matching kidneys for transplantation into children is not feasible due to limited organ availability from paediatric donors, resulting in prolonged waiting list times. Transplanting a comparatively large adult kidney into a child may lead to potential challenges related to the surgical incision and approach, vessel anastomoses, wound closure, postoperative cardiovascular stability, and age-correlated maturation of the graft. Conclusion. The transplantation of an adult kidney into a size mismatched paediatric recipient significantly reduces waiting times for surgery; however, it presents further challenges in terms of both the surgical procedure and the post-operative management of the patient's physiological parameters.

Anatomical changes in the primary visual cortex of the congenitally blind Crx-/- mouse.

Mutations in the human cone-rod homeobox (Crx) gene are associated with retinal dystrophies such as Leber Congenital Amaurosis (LCA), characterized by complete or near complete absence of vision from birth. The photoreceptors of Crx-/- mice lack outer segments, and therefore cannot capture light signals through rods and cones, thus resulting in a lack of normal retinal ganglion cell activity from birth. Using specific antibodies to subsets of neurons and markers of activity, we examined the impact of this absence of sensory input on the development of the primary visual cortex (V1) in early postnatal Crx-/- mice, before wiring of the visual system is complete, and in adulthood. We revealed that Crx-/- mice did not exhibit gross anatomical differences in V1; however, they exhibited significantly fewer calcium-binding protein (parvalbumin and calbindin-D28k) expressing interneurons, as well as reduced nonphosphorylated neurofilament expression in V1. These results reveal that the Crx mutation and lack of light stimulation through the photoreceptor pathway regulate the development and phenotype of different neuronal populations in V1 but not its general morphology. We conclude, therefore, that photoreceptor-mediated visual input during development is crucial for the normal postnatal development and maturation of subsets of cortical neurons.

The rat temporal association cortical area 2 (Te2) comprises two subdivisions that are visually responsive and develop independently.

In this study, we have used the expression of non-phosphorylated neurofilament (NNF), a protein that exhibits differential areal and laminar neuronal patterning, to assess the chemoarchitectural organization of the rat temporal association cortex (Te). Since expression of NNF is associated with the latter stages of neuronal development, this enabled us to profile the hierarchical development of this region of the cortex. We also examined the expression of the protein Fos, the product of the immediate-early gene cFos, as a neuronal activity marker to determine which areas within this region are visually responsive. Our findings reveal the existence of two previously undescribed subdivisions within the dorsal and ventral domains of the rat temporal association cortical area 2 (Te2) which we have termed Te2d and Te2v, respectively. We also demonstrated the early maturation of the caudal region of Te2d while preceding the primary visual cortex. Within this region of the cortex, the Fos protein indicates that both subdivisions are visually responsive.

No evidence of Mycobacterium avium subsp. paratuberculosis in in vitro produced cryopreserved embryos derived from subclinically infected cows.

The aim of the project was to ascertain if Mycobacterium avium subsp. paratuberculosis (Map) could be cultured from frozen-thawed in vitro produced (IVP) embryos derived from cows with subclinical Johne's disease (JD). Straws of 109 IVP embryos were obtained from 267 cumulus-oocyte-complexes (COCs) collected from 12 clinically normal cows in which antibodies against Map were detected in blood by an enzyme-linked immunosorbent assay (ELISA). These embryos were processed, washed using the standard protocol as described by the International Embryo Transfer Society (IETS) and frozen in a commercial IVP embryo laboratory. Of the 12 donor cows, 11 had histopathological or bacteriological evidence of infection at post-mortem inspection. The frozen embryos were thawed and the contents of the straws were cultured using the radiometric mycobacterial culture method. No Map was detected in any of the 109 embryos or freezing media. This suggests that the use of in vitro produced and cryopreserved embryos derived from cows with subclinical JD poses very low, if any, risk of spreading infection to susceptible animals.

Herd-level risk factors associated with tuberculosis breakdowns among cattle herds in England before the 2001 foot-and-mouth disease epidemic.

A case-control study of the factors associated with the risk of a bovine tuberculosis (TB) breakdown in cattle herds was undertaken within the randomized badger culling trial (RBCT). TB breakdowns occurring prior to the 2001 foot-and-mouth disease epidemic in three RBCT triplets were eligible to be cases; controls were selected from the same RBCT area. Data from 151 case farms and 117 control farms were analysed using logistic regression. The strongest factors associated with an increased TB risk were movement of cattle onto the farm from markets or farm sales, operating a farm over multiple premises and the use of either covered yard or 'other' housing types. Spreading artificial fertilizers or farmyard manure on grazing land were both associated with decreased risk. These first case-control results from the RBCT will be followed by similar analyses as more data become available.

Single-unit responses to kinetic stimuli in New World monkey area V2: physiological characteristics of cue-invariant neurones.

In order to investigate the neural processes underlying figure-ground segregation on the basis of motion, we studied the responses of neurones in the second visual area (V2) of marmoset monkeys to stimuli that moved against dynamic textured backgrounds. The stimuli were either "solid" bars, which were uniformly darker or lighter than the background's average, or kinetic ("camouflaged") bars, formed by textural elements that matched the spatial and temporal modulation of the background. Camouflaged bars were rendered visible only by the coherent motion of their textural elements. Using solid bars, we subdivided the population of marmoset V2 neurones into motion-selective (uni- and bi-directional units, 73.3% of the sample) and weakly-biased (26.7%) subpopulations. The motion selective subpopulation was further subdivided into cue-invariant neurones (units which demonstrated a similar selectivity for the direction of motion of the solid and camouflaged bars) and non-cue-invariant neurones (units which showed selectivity to the direction of motion of solid bars, but had weak or pandirectional responses to camouflaged bars). Cells with cue-invariant responses to these stimuli were as common in V2 as in the primary visual area (V1; approximately 40% of the population). In V2, neurones with cue-invariant and non-cue-invariant motion selectivity formed distinct populations in terms of classical response properties: cue-invariant neurones were characterized by a sharp axis of motion selectivity and extensive length summation, while the majority of non-cue-invariant neurones had broader motion selectivity and were end-stopped. In the light of previous studies, these different constellations of classical response properties suggest a correlation with more traditionally recognized categories of V2 units and modular compartments. The responses of V2 cells to kinetic stimuli were slightly delayed relative to their responses to luminance-defined stimuli.

First- and second-order stimulus length selectivity in New World monkey striate cortex.

Motion is a powerful cue for figure-ground segregation, allowing the recognition of shapes even if the luminance and texture characteristics of the stimulus and background are matched. In order to investigate the neural processes underlying early stages of the cue-invariant processing of form, we compared the responses of neurons in the striate cortex (V1) of anaesthetized marmosets to two types of moving stimuli: bars defined by differences in luminance, and bars defined solely by the coherent motion of random patterns that matched the texture and temporal modulation of the background. A population of form-cue-invariant (FCI) neurons was identified, which demonstrated similar tuning to the length of contours defined by first- and second-order cues. FCI neurons were relatively common in the supragranular layers (where they corresponded to 28% of the recorded units), but were absent from layer 4. Most had complex receptive fields, which were significantly larger than those of other V1 neurons. The majority of FCI neurons demonstrated end-inhibition in response to long first- and second-order bars, and were strongly direction selective. Thus, even at the level of V1 there are cells whose variations in response level appear to be determined by the shape and motion of the entire second-order object, rather than by its parts (i.e. the individual textural components). These results are compatible with the existence of an output channel from V1 to the ventral stream of extrastriate areas, which already encodes the basic building blocks of the image in an invariant manner.

Changes in striatal electroencephalography and neurochemistry induced by kainic acid seizures are modified by dopamine receptor antagonists.

We investigated the involvement of striatal dopamine release in electrographic and motor seizure activity evoked by kainic acid in the guinea pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the dopamine D(1) receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390; 0.5 mg kg(-1)), or the dopamine D(2) antagonist, (5-aminosulphonyl)-N-[(1-ethyl-2-pyrrolidinyl)-methyl]-2-methoxybenzamide (sulpiride, 30 mg kg(-1)). Microdialysis and high performance liquid chromatography were used to monitor changes in extracellular levels of striatal dopamine and its metabolites, glutamate, aspartate and gamma-amino-butyric acid (GABA). These data were correlated with changes in the striatal and cortical electroencephalographs and clinical signs. We found that, although neither dopamine receptor antagonist inhibited behavioural seizure activity, blockade of the dopamine D(1)-like receptor with SCH 23390 significantly reduced both the 'power' of the electrical seizure activity and the associated change in extracellular striatal concentration of glutamate, whilst increasing the extracellular striatal concentration of GABA. In contrast, blockade of the dopamine D(2)-like receptor with sulpiride significantly increased the extracellular, striatal content of glutamate and the dopamine metabolites. These results confirm previous evidence in other models of chemically-evoked seizures that antagonism of the dopamine D(1) receptor tends to reduce motor and electrographic seizure activity as well as excitatory amino-acid transmitter activity, while antagonism of the dopamine D(2) receptor has relatively less apparent effect.

Overcoming barriers to hepatitis B immunisation by a dedicated hepatitis B immunisation service.

AIMS: To determine the effectiveness of a selective hospital based hepatitis B immunisation programme and the barriers to be overcome in obtaining a successful outcome. METHODS: Retrospective case note review of 265 infants born over a five year period to hepatitis B carrier mothers at a university affiliated hospital in Hackney, London. RESULTS: A total of 242 infants (91%) were fully vaccinated; 217 (82%) had serology; 31 required booster doses. Percentages failing to reach second, third vaccinations, and serology on schedule rose exponentially (7%, 18%, 33% respectively). Mobility was high (25%) and significantly affected outcome. A total of 95% Hackney resident babies were fully vaccinated compared with 78% non-residents. Uptake of routine immunisations was higher in Hackney residents than non-residents and greater in those who were eligible for hepatitis B vaccine. Name changes occurred in 35%. Translation requirements were high (85% for Turkish, Vietnamese, and Asian families). Requirements for specific postnatal counselling of mothers and hepatology referral fell significantly during the course of the study. Only seven of 22 babies born in 1995 in Tower Hamlets compared with 53 of 58 Hackney babies received a full vaccination course in non-hospital based primary care. CONCLUSION: In inner city areas with high prevalence of hepatitis B carriage, mobility, and diverse ethnicity, a dedicated centralised immunisation service can be highly effective, provided that adequate support services (translation, counselling, and parental referral) are available.

SCH 23390 affords protection against soman-evoked seizures in the freely moving guinea-pig: a concomitant neurochemical, electrophysiological and behavioural study.

We studied the role of striatal dopamine (DA) release in seizure activity evoked by the subcutaneous administration of the cholinesterase inhibitor pinacolyl methylphosphonofluoridate (soman), in the guinea-pig. The involvement of the dopamine receptor subtypes was studied by systemic administration of the D(1)-like receptor antagonist SCH 23390 (0.5 mg kg(-1)) or the D(2)-like receptor antagonist sulpiride (30 mg kg(-1)). Microdialysis and HPLC with electrochemical detection were used to monitor changes in extracellular levels of striatal DA and its metabolites, acetylcholine and choline. These data were correlated with changes in the striatal and cortical electroencephalogram and observation of predefined clinical signs. We found that the blockade of the D(1) receptor with SCH 23390 can inhibit seizure activity, while blockade of the D(2) receptor with sulpiride can augment the evoked seizure activity. These results clarify the involvement of the dopaminergic system in soman-evoked seizures.