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Megaprostheses are increasingly utilised outside of the oncological setting, and remain at significant risk of periprosthetic joint infection (PJI). Debridement, antibiotic, and implant retention (DAIR) is an established treatment for PJI, however its use in non-oncological patients with femoral megaprostheses has not been widely reported. There are significant differences in patient physiology, treatment goals, and associated risks between these patient cohorts.We identified 14 patients who underwent DAIR for a PJI of their femoral megaprostheses, between 2000 and 2014, whom had their index procedure secondary to non-oncological indications. Patients were managed as part of a multidisciplinary team, with our standardised surgical technique including exchange of all mobile parts, and subsequent antibiotic therapy for a minimum of 3 months. Patients were followed up for a minimum of 5 years.Patients included six proximal femoral replacements, five distal femoral replacements, and three total femoral replacements. No patients were lost to follow-up. There were six males and eight females, with a mean age of 67.2 years, and mean ASA of 2.3. Nine patients (64.3%) successfully cleared their infection following DAIR at a minimum of 5 year follow-up. Five patients (35.7%) required further revision surgery, with four patients cleared of infection. No patients who underwent DAIR alone suffered complications as a result of the procedure.The use of DAIR in these complex patients can lead to successful outcomes, but the risk of further revision remains high. The success rate (64.3%) remains on par with other studies evaluating DAIR in megaprostheses and in primary arthroplasty. This study indicates judicious use of DAIR can be an appropriate part of the treatment algorithm.II.

Introduction We have seen unparalleled changes in our healthcare systems globally as a result of the COVID-19 pandemic. As we strive to regenerate our full capacity elective services in order to contest the increasing demand for lower limb arthroplasty, this pandemic has allowed us a rare opportunity to revise and develop novel elective arthroplasty pathways intended to improve patient care and advance healthcare efficiency. We present an extensive evidence-based review of the approaches used to achieve day-case unicompartmental arthroplasty (UKA) as well as the development of a day-case UKA care pathway in a UK NHS institution based on the evidence provided in the literature. Methods An extensive search of the literature was performed for articles that reported on readmission or complication rates ≥30 days postoperatively following day-case UKA. Findings Fifteen manuscripts reporting the results of day-case UKA, defined as discharged on the same calendar day of surgery, were included in our review. Mean reported complication rates for day-case and inpatient UKA within the follow-up periods were 4.05% and 6.52%, respectively. Mean readmission rates were 2.71% and 4.36% for day-case and inpatient UKA, respectively. The mean rate of successful same-day discharge was 92.45%. Conclusion We introduce our institutional Elective Day Surgery Arthroplasty Pathway (EDSAP) founded upon the evidence presented in the literature. Stringent patient selection complimented by a well-defined day-case arthroplasty pathway is fundamental for successful commencement of day-case UKA in the NHS.

Central to the basis of ecological immunology are the ideas of costs and trade-offs between immunity and life history traits. As a physical barrier, the insect cuticle provides a key resistance trait, and Tenebrio molitor shows phenotypic variation in cuticular colour that correlates with resistance to the entomopathogenic fungus Metarhizium anisopliae. Here we first examined whether there is a relationship between cuticular colour variation and two aspects of cuticular architecture that we hypothesised may influence resistance to fungal invasion through the cuticle: its thickness and its porosity. Second, we tested the hypothesis that tyrosine, a semi-essential amino acid required for immune defence and cuticular melanisation and sclerotisation, can act as a limiting resource by supplementing the larval diet and subsequently examining adult cuticular colouration and thickness. We found that stock beetles and beetles artificially selected for extremes of cuticular colour had thicker less porous cuticles when they were darker, and thinner more porous cuticles when they were lighter, showing that colour co-varies with two architectural cuticular features. Experimental supplementation of the larval diet with tyrosine led to the development of darker adult cuticle and affected thickness in a sex-specific manner. However, it did not affect two immune traits. The results of this study provide a mechanism for maintenance of cuticular colour variation in this species of beetle; darker cuticles are thicker, but their production is potentially limited by resource constraints and differential investments in resistance mechanisms between the sexes.

Recent studies have provided evidence that late-onset Alzheimer’s disease (AD) can in part be considered a metabolic disease. Besides age, female sex andAPOEε4 genotype represent strong risk factors for AD. They also both give rise to large metabolic differences, suggesting that metabolic aspects of AD pathogenesis may differ between males and females and betweenAPOEε4 carriers and non-carriers. We systematically investigated group-specific metabolic alterations by conducting stratified association analyses of 140 metabolites measured in serum samples of 1,517 AD neuroimaging initiative subjects, with AD biomarkers for Aβ and tau pathology and neurodegeneration. We observed substantial sex differences in effects of 15 metabolites on AD biomarkers with partially overlapping differences forAPOEε4 status groups. These metabolites highlighted several group-specific alterations not observed in unstratified analyses using sex andAPOEε4 as covariates. Combined stratification by both variables uncovered further subgroup-specific metabolic effects limited to the group with presumably the highest AD risk:APOEε4+ females. Pathways linked to the observed metabolic alterations suggest that females experience more expressed impairment of mitochondrial energy production in AD than males. These findings indicate that dissecting metabolic heterogeneity in AD pathogenesis may enable grading of the biomedical relevance of specific pathways for specific subgroups. Extending our approach beyond simple one- or two-fold stratification may thus guide the way to personalized medicine.Significance statementResearch provides substantial evidence that late-onset Alzheimer’s disease (AD) is a metabolic disease. Besides age, female sex and APOEε4 genotype represent strong risk factors for AD, and at the same time give rise to large metabolic differences. Our systematic investigation of sex and APOE ε4 genotype differences in the link between metabolism and measures of pre-symptomatic AD using stratified analysis revealed several group-specific metabolic alterations that were not observed without sex and genotype stratification of the same cohort. Pathways linked to the observed metabolic alterations suggest females are more affected by impairment of mitochondrial energy production in AD than males, highlighting the importance of tailored treatment approaches towards a precision medicine approach.

Toxic soft-shell clams ( Mya arenaria ) were collected and the meats homogenized and tested for toxicity by the A.O.A.C. mouse bioassay procedure. The homogenate was incubated at temperatures ranging from 220 to 269.5°F and toxicities measured in samples heated for various time intervals. The relationships between toxicity and the time of heating were semilogarithmic for each of the six incubation temperatures. Decimal reduction times were calculated for each heat treatment and were plotted (log scale) against heating temperature. The thermal-destruction-time (TDT) curve was linear (r2 = 0.97), indicating that the kinetics of paralytic shellfish poison destruction are similar to those of most microorganisms. The toxin levels were also analyzed by high performance liquid chromatography for 110 samples and although results compared favorably with the bioassay data, its reliability for routine assessment of toxicity was not clearly established.

Clearance of intracellular pathogens, such asLeishmania (L.) major, depends on a well-regulated adaptive T cell response. Here we describe a pathogen-encoded mechanism to alter T cell recruitment by suppressing CXCL10, a chemokine that recruits CD4+ and CD8+ T cells by signaling through the CXCR3 receptor.L. majorsuppresses CXCL10 through the virulence factor and protease, glycoprotein-63(gp63).GP63 cleaves CXCL10 after amino acid A81, impairing T-cell chemotaxisin vitro.GP63 from either extracellular promastigotes or intracellular amastigotes is capable of cleaving CXCL10. Consistent with CXCL10 cleavage during infection, we observed GP63-mediated impairment of activated CD8+ T-cells in the draining lymph nodes of C57BL/6JWTmice. Correspondingly, in C57BL/6JWTmice,gp63deletion resulted in slower lesion development and a smaller maximum lesion size. However, infection in C57BL/6Jcxcr3−/−mice revealed the delay to lesion development required CXCR3 signaling. Finally,Salmonella entericaandChlamydia trachomatisinfection also suppress CXCL10, demonstrating convergent evolution of this immune evasion strategy in diverse intracellular pathogens. Understanding mechanisms of CXCL10 evasion may facilitate the development of novel therapeutic strategies to treat intracellular pathogens.Author SummaryLeishmaniasis is an infectious disease that affects over one million people annually. It is caused by intracellular parasites that have evolved to evade the host’s attempts to eliminate the parasite. The most common form of disease, cutaneous leishmaniasis, causes disfiguring skin lesions if the host immune system does not appropriately respond to the infection. A family of molecules called chemokines are critical for the recruitment of specific subsets of immune cells required to eliminate infection. Here, we demonstrate a novel mechanism that the parasiteLeishmania (L.) majoremploys to disrupt the immune response by interfering with chemokine signaling. By this strategy,L. majoruses a protease to cleave chemokines known to recruit T-cells required for fighting off infection. We show thatL. majorcleavage of these immune signals changes the recruitment of CD8+ T-cells and alters disease progression in mice. Finally, we observe that multiple common human intracellular pathogens, includingChlamydia trachomatisandSalmonella enterica, interfere with the same chemokines, suggesting a strong selective pressure to avoid this component of the immune response. Our study provides new insights into how intracellular pathogens interact with the host immune response to enhance pathogen survival and exacerbate disease outcomes.

The substrate of the methionine salvage pathway, methylthioadenosine, is a predictor of death in sepsis patients., Sepsis is a deleterious inflammatory response to infection with high mortality. Reliable sepsis biomarkers could improve diagnosis, prognosis, and treatment. Integration of human genetics, patient metabolite and cytokine measurements, and testing in a mouse model demonstrate that the methionine salvage pathway is a regulator of sepsis that can accurately predict prognosis in patients. Pathway-based genome-wide association analysis of nontyphoidal Salmonella bacteremia showed a strong enrichment for single-nucleotide polymorphisms near the components of the methionine salvage pathway. Measurement of the pathway’s substrate, methylthioadenosine (MTA), in two cohorts of sepsis patients demonstrated increased plasma MTA in nonsurvivors. Plasma MTA was correlated with levels of inflammatory cytokines, indicating that elevated MTA marks a subset of patients with excessive inflammation. A machine-learning model combining MTA and other variables yielded approximately 80% accuracy (area under the curve) in predicting death. Furthermore, mice infected with Salmonella had prolonged survival when MTA was administered before infection, suggesting that manipulating MTA levels could regulate the severity of the inflammatory response. Our results demonstrate how combining genetic data, biomolecule measurements, and animal models can shape our understanding of disease and lead to new biomarkers for patient stratification and potential therapeutic targeting.

SummaryPlasma proteins mediate thrombogenesis, inflammation, endocardial injury and structural remodelling in atrial fibrillation (AF). We hypothesised that anti-coagulation with rivaroxaban, a direct factor Xa inhibitor, would differentially modulate biologically-relevant plasma proteins, compared with warfarin, a multi-coagulation protein antagonist. We performed unbiased liquid chromatography/tandem mass spectroscopy and candidate multiplexed protein immunoassays among Japanese subjects with non-valvular chronic AF who were randomly assigned to treatment with 24 weeks of rivaroxaban (n=93) or warfarin (n=94). Nine metaproteins, including fibulin-1 (p=0.0033), vitronectin (p=0.0010), haemoglobin α(p=0.0012), apolipoproteins C-II (p=0.0017) and H (p=0.0023), complement C5 precursor (p=0.0026), coagulation factor XIIIA (p=0.0026) and XIIIB (p=0.0032) subunits, and 10 candidate proteins, including thrombomodulin (p=0.0004), intercellular adhesion molecule-3 (p=0.0064), interleukin-8 (p=0.0007) and matrix metalloproteinase-3 (p=0.0003), were differentially expressed among patients with and without known clinical risk factors for stroke and bleeding in AF. Compared with warfarin, rivaroxaban treatment was associated with a greater increase in thrombomodulin (Δ0.1 vs. 0.3 pg/ml, p=0.0026) and a trend towards a reduction in matrix metalloproteinase-9 (Δ2.2 vs. –4.9 pg/ml, p=0.0757) over 24 weeks. Only modest correlations were observed between protein levels and prothrombin time, factor Xa activity and prothrombinase-induced clotting time. Plasma proteomics can identify distinct functional patterns of protein expression that report on known stroke and bleeding risk phenotypes in an ethnically-homogeneous AF population. The greater upregulation of thrombomodulin among patients randomised to rivaroxaban represents a proof-of-principle that pharmacoproteomics can be employed to discern novel effects of factor Xa inhibition beyond standard pharmacodynamic measures.

In this article we examine harmonic mappings defined on the punctured unit disk in the spirit of Clunie and Sheil-Small [J. Clunie and T. Sheil-Small (1984). Harmonic univalent functions. Ann. Acad. Sci. Fenn. Series A. I. Math., 9, 3–25] and Hengartner and Schober [W. Hengartner and G. Schober (1987). Univalent harmonic functions. Trans. Amer. Math. Soc., 299, 1–31]. We develop a family of mappings such that the members possess finitely many terms in their power series form. Moreover, there is a close coefficient relation between the analytic and co-analytic parts to guarantee the mappings are sense-preserving. After developing the family, we examine conditions for which mappings from the family are sense-preserving, typically real, and univalent, calling this family UTF. In closing, an example of the coefficient region for the sub-class of degree four UTF is included.

Measurement of insect immune effector system function aimed at identifying costs has largely been stimulated by the ideas of Hamilton & Zuk (1982), who proposed that choosy females may derive some genetic benefit from selecting parasite-resistant males. Field studies of such systems assume that most variation in measured immune traits is affected strongly by genes and pay little attention subsequently to the role of nutritional status in determining the magnitude of assayed immune effector systems. In this paper the effects of nutrient deprivation on immune function are measured in the mealworm beetle (Tenebrio molitor L.) reared in otherwise ideal conditions. The results suggest that immune effector system function is down-regulated during short-term nutritional deprivation, but is rapidly up-regulated to pre-deprivation levels after animals are allowed access to food. This rapid modulation of immune function in the context of nutritional status has important implications for measuring immune function in the field, as well as the interpretation of those measures.

The argument principle is an important and useful result for meromorphic functions on domains in the plane. Duren, Hengartner and Laugesen have obtained an argument principle for harmonic mappings on Jordan domains. This paper is concerned with proving an argument principle for harmonic mappings that have isolated singularities. Examples are included to show how the geometric behavior of harmonic mappings differs from the meromorphic case. Also included in the paper is a definition of “pole” at an isolated singular point of a harmonic mapping and a “partitioning theorem” for the image space that yields components whose values are assumed the same number of times in the appropriate region.

OBJECTIVE: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. DESIGN: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of

Summary Recently, the analgesic effects of acupuncture have been brought into question, mainly because of the methodological inadequacies of previous studies. This single-blind placebo-controlled study examined the effects of manual acupuncture administered at a point related to the site of electrically induced pain at the finger (i.e. Pericardium 6 ) and a point unrelated to the site of electrically induced pain (i.e. Gallbladder 20) in normal subjects. The effects of acupuncture on the amplitudes of the late waveform components of the somatosensory evoked potentials elicited by painful electrical stimulation of the index finger were also examined. The main findings of this study were that, when compared to sham acupuncture or control groups, acupuncture administered at either Pericardium 6 or Gallbladder 20 did not significantly change: (i) sensory detection threshold, pain threshold or pain tolerance to electrically induced pain administered to the index finger, and (ii) P 1 N 1 or N 1 P 2 amplitudes of late latency waveform components of the somatosensory evoked potentials elicited by a painful electrical stimulus delivered to the index finger. Although acupuncture appears to be successful in relieving the pain of many chronic pain sufferers, these findings substantiate recent meta-analyses which conclude that the analgesic effects of acupuncture under placebo-controlled conditions remain in doubt. Our results should serve as an incentive for further research into the analgesic effects of acupuncture under placebo-controlled conditions.

Objective Animal work suggests that maternal oxytocin secretion is influenced by the secretion of endogenous opioids in pregnancy. Spontaneous labour and pre-labour uterine activity follow a 24-hour rhythm the origin of which has not been explained but may be related to diurnal changes in oxytocin secretion. This study was performed to document the changes over a 24-hour period in maternal oxytocin and beta-endorphin secretion. Design A 4-hourly blood profile was undertaken for a 24-hour period. Patients Sixteen women with singleton pregnancies of more than 36 weeks gestation and 10 women with pregnancies in the mid trimester were studied. Measurements Blood was sampled 4-hourly for 24 hours beginning at 1200 h. Oxytocin was measured in all patients and beta-endorphin-like immunoreactivity was measured in 15 patients. Results A simple index was defined for comparing night-time levels to daytime levels for both oxytocin and beta-endorphin. In all cases more than 36 weeks gestation the index was positive for oxytocin (night-time levels were higher) and in all cases the index was negative for beta-endorphin (night-time levels were lower). In the mid trimester women all values of the index for oxytocin were positive but in the beta-endorphin group equal numbers demonstrated a positive or a negative index. Conclusions Reciprocal 24-hour rhythms were demonstrated between oxytocin and beta-endorphin; however, it is not clear whether this relationship is causal.

Electroanalgesia has been practised since ancient times, but had not gained widespread popularity with patients until the advent of transcutaneous electrical nerve stimulators in the 1970s. These electrical stimulator units have now been developed into highly effective relievers of pain, offering significant long term benefit to around 40% of chronic pain sufferers. A number of variations to the units have been designed to improve the efficacy of stimulation, however there remain 3 basic forms: continuous, pulsed and acupuncture-like. Before rejecting the method as ineffective for any patient, it is important to have an adequate trial of treatment of at least a fortnight during which all forms of available stimulation are tried, with electrodes placed in a variety of positions on the skin for a minimum of an hour at a time. Failure is generally due to lack of perseverence or unrealistic expectations.

Background Label-free quantitative proteomics holds a great deal of promise for the future study of both medicine and biology. However, the data generated is extremely intricate in its correlation structure, and its proper analysis is complex. There are issues with missing identifications. There are high levels of correlation between many, but not all, of the peptides derived from the same protein. Additionally, there may be systematic shifts in the sensitivity of the machine between experiments or even through time within the duration of a single experiment. Results We describe a hierarchical model for analyzing unbiased, label-free proteomics data which utilizes the covariance of peptide expression across samples as well as MS/MS-based identifications to group peptides—a strategy we call metaprotein expression modeling. Our metaprotein model acknowledges the possibility of misidentifications, post-translational modifications and systematic differences between samples due to changes in instrument sensitivity or differences in total protein concentration. In addition, our approach allows us to validate findings from unbiased, label-free proteomics experiments with further unbiased, label-free proteomics experiments. Finally, we demonstrate the clinical/translational utility of the model for building predictors capable of differentiating biological phenotypes as well as for validating those findings in the context of three novel cohorts of patients with Hepatitis C. Conclusions Mass-spectrometry proteomics is quickly becoming a powerful tool for studying biological and translational questions. Making use of all of the information contained in a particular set of data will be critical to the success of those endeavors. Our proposed model represents an advance in the ability of statistical models of proteomic data to identify and utilize correlation between features. This allows validation of predictors without translation to targeted assays in addition to informing the choice of targets when it is appropriate to generate those assays.

1 Three hypothalamic regulatory hormones, thyrotrophin-releasing hormone (TRH), luteinizing hormone/follicle-stimulating hormone-releasing hormone (LH/FSH-RH) and growth hormone-release inhibiting hormone (GH-RIH) given intravenously had no effect on the electroencephalographic response known as the contingent negative variation (CNV) in normal subjects. 2 TRH was given as a 10 ml infusion of 600 μg over 8 min to six subjects. This produced subjective sensations and a rise in heart rate but no significant alteration of CNV magnitude. 3 LH/FSH-RH was given in a dose of 200 μg in 10 ml over 2 min to six subjects. This had no effect on CNV magnitude or heart rate and produced no subjective effects. 4 GH-RIH was given as a 10 ml infusion of 250 μg over 10 min to six subjects. Again there was no alteration in the magnitude of the CNV; the heart rate was slowed.

Three patients with unilateral auditory disturbances (singing voices, rockets and gongs, and whistling kettles) are described. The symptoms occurred during benzodiazepine withdrawal in two patients and the instigation of nefopam treatment in one. All patients had mild hearing loss and abnormal auditory evoked potentials. Two showed marked asymmetry of background EEG rhythms over the temporal lobe. In two of the patients the symptoms responded partially to TENS and/or acupuncture.

Dit diepgaande onderzoek richtte zich op de relaties tussen patient-, stimulator- en uitkomstvariabelen van een groot aantal chronische pijnpatienten, bij wie tens langdurig was toegepast: 179 patienten vulden een tens-vragenlijst in, met als onderdelen de leeftijd, geslacht, oorzaak en lokalisatie van de pijn en het tens- behandelregiem. Van deze 179 patienten bezochten er 107 onze onderzoeks- afdeling voor evaluatie van de elektrische karakteristieken van de tens tijdens de zelf toegepaste behandeling.

The tsetse fly (Glossina spp.) inhabits 11 million km2 of Africa (Greekmore, 1989) where it is responsible for the transmission of trypanosomosis to man and animals. Because of its slow rate of reproduction, with females producing only four to five pupae per annum, control of the tsetse fly is the best means of controlling trypanosomosis. A number of different methods have been and are used but, whilst successes have been achieved, a long term solution has not been found.

The present study examines the effects of auricular transcutaneous electrical nerve stimulation (TENS) on electrical pain threshold measured at the ipsilateral wrist and autonomic functions including skin temperature, blood pressure and pulse rate in 24 healthy subjects. TENS was administered as low frequency trains of pulses delivered at a 'strong but comfortable' intensity to 1 of 3 auricular points to be examined: (i) autonomic effects (autonomic point), (ii) pain threshold effects (wrist point), and (iii) placebo effects at an unrelated point (face point). A fourth untreated group was designated as a situation control. The main finding of the study was that auricular TENS produced no significant overall effects on experimental pain threshold or autonomic functions recorded under the present conditions. However, pain threshold was found to increase by over 50% of its pretreatment baseline in 4 subjects and by 30% in 6 subjects. This rise was not dependent upon the site of auricular TENS. The possible mechanisms of such changes are discussed.

This study records the consistency of transcutaneous electrical nerve stimulation (TENS) pulse frequency and pulse pattern used by 13 chronic patients over a 1 year period. The results show that patients prefer specific pulse frequencies and pulse patterns unique to the individual and that they turn to such frequencies and patterns on subsequent treatment sessions. Pulse frequencies and pulse patterns were not related to the cause and site of pain, a finding consistent with previous study in this laboratory. This observation, coupled with the large variability in pulse frequencies and pulse patterns used between individuals, implies that patients prefer such frequencies and patterns for reasons of comfort which may not be related to mechanisms specific to the pain system.

This in-depth study examines the relationships between patient, stimulator and outcome variables in a large number of chronic pain patients utilising TENS on a long-term basis. 179 patients completed a TENS questionnaire designed to record age, sex, cause and site of pain and TENS treatment regime. Of these 179 patients, 107 attended our research unit for assessment of the electrical characteristics of TENS during self-administered treatment. Although a remarkable lack of correlation between patient, stimulator and outcome variables was found to exist, the analysis revealed much information of importance: 47% of patients found TENS reduced their pain by more than half; TENS analgesia was rapid both in onset (less than 0.5 h in 75% patients) and in offset (less than 0.5 h in 51% patients); one-third of patients utilised TENS for over 61 h/week; pulse frequencies between 1 and 70 Hz were utilised by 75% of patients; 44% of patients benefitted from burst mode stimulation. The clinical implications of these findings are discussed.

The analgesic efficacy of various pulse patterns of transcutaneous electrical nerve stimulation (TENS) were assessed in 84 normal healthy subjects using the cold pressor pain technique. Burst, modulation, random and continuous TENS all significantly elevated ice pain threshold. Continuous (80 Hz) TENS produced the greatest mean elevation in threshold but the response to random TENS showed the least inter-subject variation. Ice pain tolerance was increased by all modes of TENS, continuous TENS producing the greatest magnitude of response, although these changes did not reach statistical significance. Increasing the size of electrodes reduced the effect of continuous TENS. The clinical implications of these findings are discussed.

Our wish to know more about the paths taken by electrical currents in electroacupuncture (EA) with special reference to the heart, particularly in patients with an implanted pacemaker, prompted us to undertake this study. Using ourselves as subjects, we have developed a safe oscillographic method to detect, visualise and record the EA currents that avoids the use of equipment requiring mains electricity. After two trials with unsatisfactory equipment, we found that the newly developed model 3425 PicoScope™ (Pico Technology Ltd), with a four channel differential amplifier input connected to a laptop PC operating in battery mode, satisfied our criteria. With this recording system, we carried out two sets of experiments in which EA was provided by a Cefar acus4™ stimulator. The results confirm that the placement of a pair of acupuncture needles for EA can be used to predict the paths taken by the stimulating currents, and thus their areas of likely influence. When the needles are placed in closely adjacent acupuncture points in a limb, there is little or no detectable spread of the currents along the limb or into the chest. By contrast, when the needles are placed far apart, the electrical currents spread widely. Thus, when each of a pair of needles is placed in a point on opposite arms, the electrical currents recorded in the area of the pectoral muscles is of an order that might trigger an abnormal cardiac rhythm in a susceptible heart or activate a cardiac pacemaker incorporating an intracardiac defibrillator (ICD). Our results confirm the guidelines for EA safe practice recommended by the British Medical Acupuncture Society (BMAS) to avoid adverse events, ie EA should not be applied such that the current is likely to traverse the heart. We can now be confident that electric fields generated by pairs of needles below the knee or elbow do not create detectable currents in the chest. It is likely that similar results would be obtained with the use of transcutaneous electrical nerve stimulation (TENS) but this remains to be established by additional experiments.

It is shown that, by using basis sets of elliptical functions in electronic structure calculations for the diatomic molecules LiH, Li2, LiHe+, BeH+ and Be2, excellent agreement with fully numerical calculations is obtained within the self-consistent field model. Total energies can be reproduced to within a few mu Hartree.

Objective . The presence of a supportive companion to women in labour has been found to reduce the duration of labour and the incidence of oxytocin augmentation. The mechanism which produces this improvement is unknown but work in animals suggests that environmental disturbance produces changes in endogenous oxytocin secretion. This study was carried out to assess maternal oxytocin secretion in relation to the presence of a supportive companion in labour. Study design . A randomised controlled trial involving allocation of unsupported women in the first stage of labour to a period of 1h with a supportive companion or 1h without. Sixteen women with uncomplicated singleton pregnancies who were in the active phase of the first stage of labour were studied. Maternal oxytocin levels were assayed by radioimmunoassay for 16min (eight specimens) before and after the support or control period. Results . There are no differences between maternal oxytocin levels in the two groups of patients. There was no difference in either of the two groups between the oxytocin levels pre and post the support/control period. Conclusions . One hour of birth support in the first stage of labour did not improve maternal oxytocin levels when compared to a control group.

Central to the conceptual basis of ecological immunity is the notion that immune effector systems are costly to produce, run, and/or maintain. Using the mealworm beetle, Tenebrio molitor, as a model we investigated two aspects of the costs of innate immunity. We conducted an experiment designed to identify the cost of an induced immune response, and the cost of constitutive investment in immunity, as well as potential interactions. The immune traits under consideration were the encapsulation response and prophylactic cuticular melanization, which are mechanistically linked by the melanin-producing phenoloxidase cascade. If immunity is costly, we predicted reduced longevity and/or fecundity as a consequence of investment in either immune trait. We found a measurable longevity cost associated with producing an inducible immune response (encapsulation). In contrast to other studies, this cost was expressed under ad libitum feeding conditions. We found no measurable costs for constitutive investment in immunity (prophylactic investment in cuticular colour).

Abstract The Paddy reservoir, located near the Foothills of the Rocky Mountains in northeast British Columbia, Canada, is a fluvioestuarine valley-filled sandstone that has moderate to high permeability. Evidence of tectonic stress has been observed during hydraulic fracture treatments in the form of excessive wellbore friction and net pressures. Historically, attempts to fracture-stimulate these wells has been difficult due to the inability to generate sufficient fracture width necessary for proppant placement. This paper presents a completion solution for the Paddy reservoir in northeast British Columbia that enabled successful placement of propped fracture treatments. Pressure response of past fracture treatments were analysed to understand the cause of past failures, and to quantify the influence of tectonicallyinduced stress. A recommended completion solution is presented which includes orientated perforating to reduce near-wellbore friction and a process for designing fracture treatments to enable successful placement of proppant. Field examples of the new completion technique are presented which show that near-wellbore friction was reduced by 50%, and that up to four times the amount of proppant was placed in the formation compared to previous treatments. Pressure match simulation results from the fracture treatments are also presented. Geologic Summary The Paddy Member forms the upper portion of the Peace River Formation and is distributed over the Peace River area of northwest Alberta and northeast British Columbia. It is underlain by dominantly coarse-grained shoreface deposits of the Cadotte Member and overlain by marine shales of the Shaftesbury Formation. The Paddy Member is made up of thinly bedded sandstones and shales with occasional thin coals. In the study area, the Paddy is approximately 40 m thick. Reservoir quality, incised valley sandstones located in the upper part of the unit are up to 18 m thick. They are dominantly fine to medium and occasionally coarse grained, fairly quartz-rich sandstones with 10 - 30% chert and other lithic grains. Beds are from centimetre to metre scale in thickness and show small to large-scale trough cross lamination. Where bedding thickness is reduced, millimetre scale wavy shale laminae are common and are often incorporated into stylolitic concentrations, which greatly reduce vertical permeability. The cleaner sandstones were probably deposited under fluvial conditions with some tidal influence where thin shale laminae are common. The dominant cement in these sandstones is quartz, which substantially occludes intergranular porosity in the study area. Small amounts of carbonate cements also occur but are rarely volumetrically important. In addition to intergranular porosity, a significant amount of microporosity has been generated through the dissolution of detrital grains, primarily chert. The abundance of microporosity in these sandstones, together with low water saturations indicated by wireline log analysis, may be the origin of the widely held concern that the Paddy reservoir is susceptible to formation damage through water blocking. Core from the study area indicates that porosity in the Paddy reservoir ranges up to 20%, with associated permeability to air at minimal confining pressure of several hundred millidarcies. A minimum porosity cutoff for pay is taken at approximately 8 - 9%, which is typically associated with 1 md permeability.

Amy D'Andrea and Jessica Sjogren 464 pages, paperback, £41.99. Wiley-Blackwell. 2013. ISBN 978 0 8138 1621 0 ![Graphic][1] THIS is a comprehensive reference guide aimed at the more experienced reader. The authors have spent some 15 years compiling the data and presenting it in an easy-to-reference format. In over 400 pages, the authors cover a wide range of subjects from preventive health care, nutrition, reproduction and anatomy to emergency and critical care; there's even a small chapter on holistic medicine. There is very little narrative text, with most of the … [1]: /embed/inline-graphic-1.gif

We studied the effects of spinal intrathecal fentanyl on oxytocin secretion in 20 healthy women prior to an elective caesarean delivery at term under spinal anaesthesia. The women were randomly allocated into two groups with respect to spinal anaesthesia. Group I (n=10) received intrathecal bupivacaine (15 mg) plus fentanyl (25 microgram), and Group II (n=10) received intrathecal bupivacaine (15 mg) alone, prior to caesarean section. The two groups were comparable demographically. Altogether, ten samples of 4.5 ml of blood (taken every 60 s) were obtained before and ten samples were obtained after the intrathecal administration of the drug and establishment of the T6 block, and plasma oxytocin concentrations were assayed for each subject. Oxytocin was measured by RIA. We found no significant differences in plasma oxytocin concentrations of individual subjects before and after intrathecal injection. In addition, there were no significant differences in plasma oxytocin concentrations between the two groups when pooled samples from the subjects were compared for the pre- and post-intrathecal injection phases. We conclude that the spinal intrathecal administration of fentanyl does not suppress oxytocin secretion in pregnant women who are not in labour at term.

Joint inflammation in juvenile rheumatoid arthritis (JRA) is sometimes associated with an autoimmune response to type II collagen (CII), a cartilage-specific protein. To test the hypothesis that down-regulation of autoimmunity to CII can be accomplished in JRA by oral administration of CII, an open-label study of CII was performed in 9 patients with JRA.Seven rheumatoid factor-negative JRA patients with polyarticular disease and 2 JRA patients with pauciarticular disease (1 with early onset and 1 with late onset) were treated for 3 months with oral bovine CII. Patients were examined for disease activity and underwent routine laboratory testing at monthly intervals. Two of the patients had flares of disease when treatment was discontinued, and these patients were re-treated for an additional 3 months. To test the hypothesis that oral tolerance induces an immune deviation of T cells, peripheral blood mononuclear cells from patients were collected before and after treatment and cultured with CII. Supernatants and RNA were collected and analyzed for the presence of various cytokines.Eight patient trials met the criteria for clinical improvement outlined by Giannini and coworkers in 1997. None of the patients had any side effects from the treatment. In 6 of the 8 patients who improved, interferon-gamma production decreased after oral CII therapy, correlating with clinical improvement, while 6 patients had increases in levels of transforming growth factor beta3.These results are encouraging. The possible beneficial effect of oral CII in JRA merits further investigation.

Despite the former popularity of hypnosis as a way of "improving" eyewitness memory, many courts almost always regard the use of this testimony to be inadmissible, whereas others allow it only when strict procedural guidelines have been followed. Although the U.S. Supreme Court recognized a defendant's constitutional right to admit his own hypnotically elicited testimony, others have recognized a constitutional basis to exclude hypnotically elicited testimony in most other circumstances.

1. Animal and human work has indicated that maternal oxytocin secretion is under the control of endogenous opiates. Previous workers have described the fetal production of oxytocin in addition to maternal production. The study of the interaction between exogenously administered opiates and oxytocin secretion may give insight into the activity of any opiate-mediated regulatory mechanism of oxytocin secretion in the fetus. This study was designed to investigate the effect of an opiate (5 mg of morphine) given to the mother on the fetal production of oxytocin in labour. 2. Morphine was given by the attending clinicians for analgesic purposes to women in the first stage of labour. After delivery umbilical artery vein and maternal vein specimens were taken. 3. Four groups of patients were studied: women after normal vaginal delivery without analgesia in labour (n=10); women after normal vaginal delivery who had morphine administration in the first stage of labour (n=12); women who had an emergency Caesarean section in the first stage of labour (n=11); women who had an elective Caesarean section at term who were not in labour (n=11). 4. Oxytocin levels were measured by radioimmunoassay in the maternal vein, umbilical artery and umbilical vein specimens. Morphine was measured by radioimmunoassay in the umbilical vein specimens. 5. The umbilical artery minus vein concentration of oxytocin was calculated for each patient (A-V). There was no change in the umbilical (A-V) concentration of oxytocin if morphine had been given to the mother in labour; this applied to fetuses delivered vaginally or by Caesarean section. When the fetuses who were exposed to morphine were analysed separately, there was no correlation between the umbilical vein morphine concentration and the umbilical (A-V) oxytocin concentration either in Caesarean or vaginal deliveries. 6. Fetal oxytocin production was not affected by the maternal administration of morphine in the first stage of labour. This applies to the oxytocin production in the first and second stage of labour.