Post-operative pain after laparoscopic right hemicolectomy for Crohn's disease: a case control study.

AIM: Surgery for Crohn's disease (CD) is characterized by an enhanced inflammatory response. While inflammation can induce hyperalgesia, post-operative pain following surgery for CD has not been characterized. This retrospective study compared a consecutive series of patients undergoing laparoscopic right hemicolectomy for CD and neoplasia performed by a single surgeon. METHOD: Elective resections performed between Jan-2016 and Aug-2017 managed in an enhanced recovery pathway were eligible for inclusion. Patients were excluded if open surgery was performed, an ileostomy was fashioned, no patient-controlled analgesia (PCA) was used or data were incomplete. Results : 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. RESULTS: 38 cases were included, 20 for neoplasia and 18 for ileocolonic CD. There was no difference in patient gender (P=0.520). CD patients were younger (39.8±2.8 Vs 77.2±2.1 years, P<0.001) but had an equivalent length of resection (312.9±43.5 Vs 283.3±71.7 mm, P=0.915). CD patients had higher pain scores on post-operative day 1 (6.8±0.8 Vs 2.6±1.0, P<0.001), day 2 (5.0±0.5 Vs 1.6±0.9, P<0.001) and day 3 (4.1±0.6 Vs 1.3±0.7, P=0.008). CD patients used their PCA for longer (85.7±16.3 Vs 47.7±4.2 hours, P=0.017) and used a greater total amount of morphine (148.6±33.8 Vs 37.0±7.8 mg, P<0.001). Post-operative CRP was higher in patients with CD on day 1 (P=0.011), day 2 (P=0.001), day 3 (P=0.001) and day 4 (P=0.007), but no leak or intra-abdominal abscess occurred in either group. CONCLUSIONS: CD patients experience increased post-operative pain, require more post-operative analgesia and have an enhanced post-operative inflammatory response. Further studies to elucidate the mechanism of this hyperalgesia and strategies to obviate it are required.

Design and initial characterization of a compact, ultra high vacuum compatible, low frequency, tilt accelerometer.

A compact tilt accelerometer with high sensitivity at low frequency was designed to provide low frequency corrections for the feedback signal of the Advanced Laser Interferometer Gravitational Wave Observatory active seismic attenuation system. It has been developed using a Tungsten Carbide ceramic knife-edge hinge designed to avoid the mechanical 1/f noise believed to be intrinsic in polycrystalline metallic flexures. Design and construction details are presented; prototype data acquisition and control limitations are discussed. The instrument's characterization reported here shows that the hinge is compatible with being metal-hysteresis-free, and therefore also free of the 1/f noise generated by the dislocation Self-Organized Criticality in the metal. A tiltmeter of this kind will be effective to separate the ground tilt component from the signal of horizontal low frequency seismometers, and to correct the ill effects of microseismic tilt in advanced seismic attenuation systems.

Tumour microenvironment of both early- and late-stage colorectal cancer is equally immunosuppressive.

BACKGROUND: Tumour microenvironment (TME) of advanced colorectal cancer (CRC) suppresses dendritic cell (DC) maturation. Here, our aim was to determine how the microenvironment of early-stage tumours influences DCs. METHODS: Tumour-conditioned media (TCM) was generated by culturing explant tumour tissue in vitro (n=50). Monocyte-derived DCs (MDDCs) of healthy donors or cancer patients were pretreated with TCM and stimulated with lipopolysaccharide (LPS). DC maturation was assessed by flow cytometry and cytokine production measured by ELISA. RESULTS: TCM from both early- and late-staged tumours abrogated LPS-induction of IL-12p70 secretion, while increasing IL-10. The profile of inflammatory mediators in TCM was similar across stages, and all increased pSTAT3 expression by DCs.CRC patient DCs (n=31) secreted low levels of IL-12p70 and failed to upregulate expression of maturation markers in response to LPS. Furthermore, in vitro culture of autologous DCs with TCM did not change the hypo-responsiveness of patient DCs. CONCLUSION: Our data demonstrates that the TME of all stages of CRC contains inflammatory mediators capable of suppressing local DCs. MDDCs obtained from CRC patients are hyporesponsive to stimuli such as LPS. Measures to reverse the negative influence of the TME on DCs will optimise cancer vaccines in both early- and late-stage CRC.

A high precision, compact electromechanical ground rotation sensor.

We present a mechanical rotation sensor consisting of a balance pivoting on a tungsten carbide knife edge. These sensors are important for precision seismic isolation systems, as employed in land-based gravitational wave interferometers and for the new field of rotational seismology. The position sensor used is an air-core linear variable differential transformer with a demonstrated noise floor of 1 × 10⁻¹¹ m/√Hz. We describe the instrument construction and demonstrate low noise operation with a noise floor upper bound of 5.7 × 10⁻9 rad/√Hz at 10 mHz and 6.4 × 10⁻¹° rad/√Hz at 0.1 Hz. The performance of the knife edge hinge is compatible with a behaviorur free of noise from dislocation self-organized criticality.

Review article: the psychosexual impact of inflammatory bowel disease in male patients.

BACKGROUND: Knowledge of the extent and the impact of sexual dysfunction and interpersonal relationships in men with inflammatory bowel disease is scarce. AIMS: The aim of this review article was to summarise the current literature on sexual function in male patients with IBD and to provide a critical review of the IBD-related medical, surgical and psychological complications that can result in impaired quality of sexual health. METHODS: To collect relevant articles, PubMed/Medline and Embase searches were performed using Boolean search phrases. RESULTS: Reported rates of sexual dysfunction in male IBD patients range from 10% to 50%. Thirty-three to fifty per cent of patients report that sexual desire and satisfaction deteriorated after IBD diagnosis. Of those patients who were sexually inactive, half of these attributed lack of intercourse to underlying IBD. A striking finding reproduced in numerous studies is that disease activity relates strongly to impaired psychological function, and the most consistently reported risk factor for sexual problems in IBD patients is co-existing mood disorders. Hypogonadism is a complication of IBD and its therapies, the role of testosterone deficiency should be further explored as a potentially treatable and reversible factor in sexual dysfunction. CONCLUSIONS: By understanding what factors contribute to poor sexual functioning in our patients, we can strive to minimise adverse psychosocial events. Further insight into this complex relationship requires an IBD-specific measure of sexual function in male patients. We recommend screening for and treating co-morbid depression, testosterone deficiency and striving for clinical remission to prevent psychosexual dysfunction in male patients with inflammatory bowel disease.

The appropriateness of a proton pump inhibitor prescription.

Proton pump inhibitors (PPIs) are one of the most commonly prescribed groups of drug in Ireland, at great expense to the Irish healthcare executive. This study aims to evaluate the appropriateness of PPI prescriptions on admission and discharge in a tertiary referral hospital. All non-elective admissions in the Emergency Department in one week were included in the study. 102 patients in total were included, with 36 (35.4%) treated with a PPI on admission. Of these, only 3 (8.3%) had a clear indication noted as per current NICE guidelines. 18 new in-hospital PPI prescriptions were documented. 11 (61%) of which were present on discharge prescriptions. Continuing PPI prescription on discharge into the community may be inappropriate, costly and potentially harmful. Brief interventions aimed at reducing inappropriate PPI prescriptions have been shown to be effective at reducing the cost and potential harm of unnecessary treatment.

Characterization, stability, and plant effects of kiln-produced wheat straw biochar.

Biochar is a promising technology for improving soil quality and sequestering C in the long term. Although modern pyrolysis technologies are being developed, kiln technologies often remain the most accessible method for biochar production. The objective of the present study was to assess biochar characteristics, stability in soil, and agronomic effects of a kiln-produced biochar. Wheat-straw biochar was produced in a double-barrel kiln and analyzed by solid-state C nuclear magneticresonance spectroscopy. Two experiments were conducted with biochar mixed into an Ap-horizon sandy loam. In the first experiment, CO efflux was monitored for 3 mo in plant-free soil columns across four treatments (0, 10, 50, and 100 Mg biochar ha). In the second experiment, ryegrass was grown in pots having received 17 and 54 Mg biochar ha combined with four N rates from 144 to 288 kg N ha. Our kiln method generated a wheat-straw biochar with carbon content composed of 92% of aromatic structures. Our results suggest that the biochar lost <0.16% C as CO over the 90-d incubation period. Biomass yields were not significantly modified by biochar treatments, except for a slight decrease at the 144 kg N ha rate. Foliar N concentrations were significantly reduced by biochar application. Biochar significantly increased soil water content; however, this increase did not result in increased biomass yield. In conclusion, our kiln-produced biochar was highly aromatic and appeared quite recalcitrant in soil but had no overall significant impact on ryegrass yields.

A national house-staff audit of medical prophylaxis in medical patients for the PREVENTion of Venous ThromboEmbolism (PREVENT-VTE).

We established a national audit to assess the thromboprophylaxis rate for venous thromoembolism (VTE) in at risk medical patients in acute hospitals in the Republic of Ireland and to determine whether the use of stickers to alert physicians regarding thromboprophylaxis would double the rate prophylaxis in a follow-up audit. 651 acute medical admission patients in the first audit and 524 in the second re-audit were recruited. The mean age was 66.5 yrs with similar numbers of male and female patients and 265 (22.6%) patients were active smokers. The first and second audits identified 549 (84%) and 487 (93%) of patients at-risk for VTE respectively. Of the at-risk patients, 163 (29.7%) and 132 (27.1%) received LMWH in the first and second audit respectively. Mechanical thromboprophylaxis was instigated in 75 (13.6%) patients in the first and 86 (17.7%) patients in the second audit. The placement of stickers in patient charts didn't produce a significant increase in the number of at risk patients treated in the second audit. There is unacceptably low adherence to the ACCP guidelines in Ireland and more complex intervention than chart reminders are required to improve compliance.

Particulate matter concentrations in residences: an intervention study evaluating stand-alone filters and air conditioners.

UNLABELLED: This study, a randomized controlled trial, evaluated the effectiveness of free-standing air filters and window air conditioners (ACs) in 126 low-income households of children with asthma. Households were randomized into a control group, a group receiving a free-standing HEPA filter placed in the child's sleeping area, and a group receiving the filter and a window-mounted AC. Indoor air quality (IAQ) was monitored for week-long periods over three to four seasons. High concentrations of particulate matter (PM) and carbon dioxide were frequently seen. When IAQ was monitored, filters reduced PM levels in the child's bedroom by an average of 50%. Filter use varied greatly among households and declined over time, for example, during weeks when pollutants were monitored, filter use was initially high, averaging 84±27%, but dropped to 63±33% in subsequent seasons. In months when households were not visited, use averaged only 34±30%. Filter effectiveness did not vary in homes with central or room ACs. The study shows that measurements over multiple seasons are needed to characterize air quality and filter performance. The effectiveness of interventions using free-standing air filters depends on occupant behavior, and strategies to ensure filter use should be an integral part of interventions. PRACTICAL IMPLICATIONS: Environmental tobacco smoke (ETS) increased particulate matter (PM) levels by about 14 µg/m3 and was often detected using ETS-specific tracers despite restrictions on smoking in the house as reported on questionnaires administered to caregivers. PM concentrations depended on season, filter usage, relative humidity, air exchange ratios, number of children, outdoor PM levels, sweeping/dusting, and presence of a central air conditioner (AC). Free-standing air filters can be an effective intervention that provides substantial reductions in PM concentrations if the filters are used. However, filter use was variable across the study population and declined over the study duration, and thus strategies are needed to encourage and maintain use of filters. The variability in filter use suggests that exposure misclassification is a potential problem in intervention studies using filters. The installation of a room AC in the bedroom, intended to limit air exchange ratios, along with an air filter, did not lower PM levels more than the filter alone.

Cultural and linguistic validation of acne-QoL in French.

BACKGROUND: Acne-Quality of Life (acne-QoL) is a facial acne-specific quality-of-life instrument developed in English. OBJECTIVE: Our objective was to translate and validate acne-QoL in French and to establish the reliability and responsivity of this measure. METHODS: Acne-QoL was translated into French (acne-QoLfr) in accordance with international methodological recommendations. The validated French version of the Cardiff Acne Disability Index (CADIfr) was used as a comparator. Acne patients in Quebec (n = 20) and France (n = 14) completed the acne-QoLfr and CADIfr on three occasions over 3 months (day 0, day 2-3, day 60-90). RESULTS: A total of 34 patients were recruited. Pearson's correlation for total acne-QoLfr scores at day 0 and day 2-3 was 0.77. Of the four domains comprising the acne-QoLfr, correlations were highest for symptoms (0.85) and lowest for the role-emotional domain (0.66). At day 60-90, total acne-QoLfr scores increased by a mean of 19.7 points, reflecting improved quality-of-life with acne therapy and demonstrating responsivity of the instrument. CONCLUSION: Acne-QoLfr is a linguistically and culturally validated tool for facial acne that is both reliable and responsive.

Blackawton bees.

BACKGROUND: Real science has the potential to not only amaze, but also transform the way one thinks of the world and oneself. This is because the process of science is little different from the deeply resonant, natural processes of play. Play enables humans (and other mammals) to discover (and create) relationships and patterns. When one adds rules to play, a game is created. THIS IS SCIENCE: the process of playing with rules that enables one to reveal previously unseen patterns of relationships that extend our collective understanding of nature and human nature. When thought of in this way, science education becomes a more enlightened and intuitive process of asking questions and devising games to address those questions. But, because the outcome of all game-playing is unpredictable, supporting this 'messyness', which is the engine of science, is critical to good science education (and indeed creative education generally). Indeed, we have learned that doing 'real' science in public spaces can stimulate tremendous interest in children and adults in understanding the processes by which we make sense of the world. The present study (on the vision of bumble-bees) goes even further, since it was not only performed outside my laboratory (in a Norman church in the southwest of England), but the 'games' were themselves devised in collaboration with 25 8- to 10-year-old children. They asked the questions, hypothesized the answers, designed the games (in other words, the experiments) to test these hypotheses and analysed the data. They also drew the figures (in coloured pencil) and wrote the paper. Their headteacher (Dave Strudwick) and I devised the educational programme (we call 'i,scientist'), and I trained the bees and transcribed the childrens' words into text (which was done with smaller groups of children at the school's local village pub). So what follows is a novel study (scientifically and conceptually) in 'kids speak' without references to past literature, which is a challenge. Although the historical context of any study is of course important, including references in this instance would be disingenuous for two reasons. First, given the way scientific data are naturally reported, the relevant information is simply inaccessible to the literate ability of 8- to 10-year-old children, and second, the true motivation for any scientific study (at least one of integrity) is one's own curiousity, which for the children was not inspired by the scientific literature, but their own observations of the world. This lack of historical, scientific context does not diminish the resulting data, scientific methodology or merit of the discovery for the scientific and 'non-scientific' audience. On the contrary, it reveals science in its truest (most naive) form, and in this way makes explicit the commonality between science, art and indeed all creative activities. PRINCIPAL FINDING: 'We discovered that bumble-bees can use a combination of colour and spatial relationships in deciding which colour of flower to forage from. We also discovered that science is cool and fun because you get to do stuff that no one has ever done before. (Children from Blackawton)'.

Experimental assessment of the probabilistic maturation reaction norm: condition matters.

The probabilistic maturation reaction norm (PMRN) describes an individual's probability of maturing at a given age as a function of size and other relevant phenotypic traits. Population-level shifts in the PMRN are often interpreted to indicate genetic as opposed to phenotypic changes in maturation in fish. Inferences derived from trends in the PMRN have been challenged, warranting an experimental assessment of the method. This was accomplished in a laboratory experiment using zebrafish (Danio rerio). Fish were reared under different food levels to induce variation in growth and maturation. Plasticity in maturation was not entirely captured by the demographic age- and length-based PMRN. Adding condition to the PMRN captured a greater amount of environmental variation in maturation probability. Nevertheless, significant differences in the PMRNs among the food levels remained after accounting for the influences of age, size and condition on maturation probability indicating plasticity of the PMRN. This was particularly pronounced between fish held on low food levels as compared with fish experiencing abundant resources, with the latter experiencing higher size-specific maturation probabilities. Our analysis emphasizes the need for incorporating salient physiological traits influencing maturation, such as condition, to make accurate inferences about documented shifts observed in the position of PMRNs on maturation trends in wild fish stocks.

Tumour necrosis factor-alpha activation of protein kinase B in WEHI-164 cells is accompanied by increased phosphorylation of Ser473, but not Thr308.

Tumour necrosis factor-alpha (TNF-alpha) may activate both cell survival and cell death pathways. In the murine fibrosarcoma cell line WEHI-164, physiological concentrations (1 ng/ml) of TNF-alpha induced wortmannin-sensitive cell ruffling characteristic of the phosphoinositide 3-kinase (PI3-kinase) activation associated with cell survival. Wortmannin also enhanced cell death induced by TNF-alpha in the presence of actinomycin D, confirming that TNF-alpha activates a transcription-independent survival pathway requiring PI3-kinase activity. Both TNF-alpha and insulin-like growth factor 1 (IGF-1) caused a 6-10-fold wortmannin-sensitive increase in protein kinase B (PKB) activity within 5 min. For IGF-1, this was associated with an increase in phosphorylation of both Thr(308) and Ser(473), whereas for TNF-alpha only phosphorylation of Ser(473) was increased, even in the presence of okadaic acid to inhibit protein phosphatases 1 and 2A. TNF-alpha did not decrease the phosphorylation of Thr(308) induced by IGF-1, implying that TNF-alpha neither inhibits phosphoinositide-dependent kinase 1 (PDK1) nor activates an opposing phosphatase. In WEHI cells overexpressing a form of PKB, IGF-1 increased phosphorylation of Ser(473) on PKB, but not its kinase activity, whereas TNF-alpha failed to induce Ser(473) phosphorylation or kinase activation of either overexpressed T308A or wild-type PKB (where T308A is the mutant bearing the substitution Thr(308)-->A). IGF-1 caused translocation of green-fluorescent-protein-tagged ADP-ribosylation factor nucleotide-binding site opener (ARNO) to the plasma membrane of WEHI cells, but this was not detected with TNF-alpha. We conclude that, at physiological concentrations, TNF-alpha activates endogenous PKB by stimulating PDK2 (increase in Ser(473) phosphorylation) in a PI3-kinase-dependent (wortmannin-sensitive) manner, without causing detectable stimulation of PDK1 (no increase in Thr(308) phosphorylation) or ARNO translocation. Possible explanations of these observations are discussed.

Prototype-referenced shape encoding revealed by high-level aftereffects.

We used high-level configural aftereffects induced by adaptation to realistic faces to investigate visual representations underlying complex pattern perception. We found that exposure to an individual face for a few seconds generated a significant and precise bias in the subsequent perception of face identity. In the context of a computationally derived 'face space,' adaptation specifically shifted perception along a trajectory passing through the adapting and average faces, selectively facilitating recognition of a test face lying on this trajectory and impairing recognition of other faces. The results suggest that the encoding of faces and other complex patterns draws upon contrastive neural mechanisms that reference the central tendency of the stimulus category.

Recognition and sex categorization of adults' and children's faces: examining performance in the absence of sex-stereotyped cues.

The ability of children and adults to classify the sex of children's and adults' faces using only the biologically based internal facial structure was investigated. Face images of 7- to 10-year-old children and of adults in their 20s were edited digitally to eliminate hairstyle and clothing cues to sex. Seven-year-olds, nine-year-olds, and adults classified a subset of these faces by sex and were asked, subsequently, to recognize the faces from among the entire set of faces. This recognition task was designed to assess the relationship between categorization and recognition accuracy. Participants categorized the adult faces by sex at levels of accuracy varying from just above chance (7-year-olds) to nearly perfect (adults). All participant groups performed less accurately for children's faces than for adults' faces. The 7-year-olds were unable to classify the children's faces by sex at levels above chance. Finally, the faces of children and adults were equally recognizable--a finding that has theoretical implications for understanding the relationship between categorizing and identifying faces.

Mitochondria and cell death.

Mitochondria play a central role in both apoptosis and necrosis through the opening of the mitochondrial permeability transition pore (MPTP). This is thought to be formed through a Ca(2+)-triggered conformational change of the adenine nucleotide translocase (ANT) bound to matrix cyclophilin-D and we have now demonstrated this directly by reconstitution of the pure components. Opening of the MPTP causes swelling and uncoupling of mitochondria which, unrestrained, leads to necrosis. In ischaemia/reperfusion injury of the heart we have shown MPTP opening directly. Recovery of hearts correlates with subsequent closure, and agents that prevent opening or enhance closure protect from injury. Transient MPTP opening may also be involved in apoptosis by initially causing swelling and rupture of the outer membrane to release cytochrome c (cyt c), which then activates the caspase cascade and sets apoptosis in motion. Subsequent MPTP closure allows ATP levels to be maintained, ensuring that cell death remains apoptotic rather than necrotic. Apoptosis in the hippocampus that occurs after a hypoglycaemic or ischaemic insult is triggered by this means. Other apoptotic stimuli such as cytokines or removal of growth factors also involve mitochondrial cyt c release, but here there is controversy over whether the MPTP is involved. In many cases cyt c release is seen without any mitochondrial depolarization, suggesting that the MPTP does not open. Recent data of our own and others have revealed a specific outer-membrane cyt c-release pathway involving porin that does not release other intermembrane proteins such as adenylate kinase. This is opened by pro-apoptotic members of the Bcl-2 family such as BAX and prevented by anti-apoptotic members such as Bcl-X(L). Our own data suggest that this pathway may interact directly with the ANT in the inner membrane at contact sites.

On the other side of the mean: the perception of dissimilarity in human faces.

We created a 'face space' using a laser-scan representation of faces. In this space, a caricature can be made by moving a face away from the average face, along the line connecting the particular face to the average face. Here, we move the face along this line in the other direction, proceeding through the mean and 'out the other side'. This results in a face that is 'opposite', in a computational sense, to the original face. We morphed several faces into their anti-faces and sampled the morph trajectory in five discrete steps. We then collected similarity ratings from human participants for all possible pairs of morphed faces to determine how the distances in the 'physical face space' related to the distances in the 'psychological face space'. The data indicate that there is a perceptual discontinuity of face identity as the face crosses over to the 'other side of the mean'. We consider these results in the context of face-space models of human face processing.

The face typicality-recognizability relationship: encoding or retrieval locus?

Using a crossover recognition memory testing paradigm, we tested whether the effects on face recognition of the memorability component of face typicality (Vokey & Read, 1992, 1995) are due primarily to the encoding process occurring during study or to the retrieval process occurring at test. At study, faces were either veridical in form or at moderate (Experiment 1) or extreme (Experiment 2) levels of caricature. The variable of degree of facial caricature at study was crossed with the degree of caricature at test. The primary contribution of increased memorability to increased hit rate was through increased distinctiveness at study. Increased distinctiveness at test contributed to substantial reductions in the false alarm rate, too. Signal detection analyses confirmed that the mirror effects obtained were primarily stimulus/memory-based, rather than decision-based. Contrary to the conclusion of Vokey and Read (1992), we found that increments in face memorability produced increments in face recognition that were due at least as much to enhanced encoding of studied faces as they were to increased rejection of distractor faces.