Does Rectoanal Intussusception Limit Improvements in Clinical Outcome and Quality of Life After Sacral Nerve Stimulation for Fecal Incontinence?

BACKGROUND: Sacral nerve stimulation is a treatment option for severe, medically refractory fecal incontinence, although its use in patients with anatomic abnormalities remains controversial. OBJECTIVE: This study aimed to determine whether patients with rectoanal intussusception achieve similar benefits from device implantation to patients without rectoanal intussusception. DESIGN: Retrospective review of a prospectively maintained database. Demographics and clinical data were collected for each patient, including preoperative pelvic floor testing. Defecographies were reanalyzed in a blinded manner. Preoperative rectoanal intussusception was determined on the basis of the Oxford system (grade III-IV vs not; grade V excluded). SETTINGS: Academic-affiliated pelvic health center. PATIENTS: All patients undergoing sacral nerve stimulation for fecal incontinence between July 2011 and July 2019. MAIN OUTCOME MEASURES: Cleveland Clinic Florida Incontinence/Wexner Scores, Fecal Incontinence Severity Indices, and Fecal Incontinence Quality of Life Indices at 1 year. RESULTS: One hundred sixty-nine patients underwent sacral nerve stimulation for fecal incontinence during the study period. The average age was 60.3 years and 91% were female. Forty-six patients (27.2%) had concomitant rectoanal intussusception (38 patients [22.5%] grade III and 8 patients [4.7%] grade IV). Before surgery, patients reported an average of 10.8 accidents per week and a Wexner score of 15.7, with no difference between patients with and without rectoanal intussusception ( p = 0.22 and 0.95). At 1 year after surgery, the average Wexner score was 9.5. There was no difference in postoperative Wexner scores (10.4 vs 9.2, p = 0.23) or improvement over time between patients with and without rectoanal intussusception (-6.7 vs -5.7, p = 0.40). Similarly, there was no difference in quality of life or frequency of incontinence to liquid or solid stool. LIMITATIONS: Single-institution, moderate sample size, incomplete survey response. CONCLUSIONS: Concomitant rectoanal intussusception does not appear to affect clinical outcomes or quality of life after sacral nerve stimulation for fecal incontinence. Appropriate patients with fecal incontinence and rectoanal intussusception can be considered for sacral nerve stimulation placement. See Video Abstract at http://links.lww.com/DCR/C192 . LA INTUSUSCEPCIN RECTOANAL LIMITA LAS MEJORAS EN EL RESULTADO CLNICO Y LA CALIDAD DE VIDA DESPUS DE LA NEUROESTIMULACION SACRA PARA LA INCONTINENCIA FECAL: ANTECEDENTES:La neuroestimulación sacra es una opción de tratamiento para la incontinencia fecal grave refractaria al tratamiento médico, aunque su uso en pacientes con anomalías anatómicas sigue siendo controvertido.OBJETIVO:Determinar si los pacientes con intususcepción rectoanal logran beneficios similares de la implantación del dispositivo a los pacientes sin intususcepción rectoanal.DISEÑO:Revisión retrospectiva de una base de datos mantenida prospectivamente. Se recopilaron datos demográficos y clínicos de cada paciente, incluidas las pruebas preoperatorias del piso pélvico. Las defecografías se volvieron a analizar de forma ciega. La intususcepción rectoanal preoperatoria se determinó según el sistema de Oxford (grado III-IV vs. no; grado V excluido).ESCENARIO:Centro académico de salud pélvica.PACIENTES:Todos los pacientes sometidos a neuroestimulación sacra por incontinencia fecal entre julio de 2011 y julio de 2019.PRINCIPALES MEDIDAS DE RESULTADO:Cleveland Clinic Florida Incontinence/Wexner Scores, Índices de gravedad de la incontinencia fecal, Índices de calidad de vida de la incontinencia fecal al año.RESULTADOS:169 pacientes se sometieron a neuroestimulación sacra por incontinencia fecal durante el período de estudio. La edad promedio fue de 60.3 años y el 91% eran mujeres. Cuarenta y seis pacientes (27.2%) tenían intususcepción rectoanal concomitante (38 [22.5%] grado III y 8 [4.7%] grado IV). Antes de la cirugía, los pacientes informaron un promedio de 10.8 accidentes por semana y una puntuación de Wexner de 15.7 sin diferencia entre pacientes con y sin intususcepción rectoanal (p = 0.22 y 0.95). Un año después de la cirugía, la puntuación promedio de Wexner fue de 9.5. No hubo diferencia en las puntuaciones de Wexner posoperatorias (10.4 frente a 9.2, p = 0.23) o mejoría con el tiempo entre los pacientes con y sin intususcepción rectoanal (-6.7 frente a -5.7, p = 0.40). De manera similar, no hubo diferencia en la calidad de vida o la frecuencia de incontinencia de heces líquidas o sólidas.LIMITACIONES:Institución única, tamaño de muestra moderado, respuesta de encuesta incompleta.CONCLUSIÓN:La intususcepción rectoanal concomitante no parece afectar los resultados clínicos o la calidad de vida después de la neuroestimulación sacra para la incontinencia fecal. Los pacientes apropiados con incontinencia fecal e intususcepción rectoanal pueden ser considerados para la neuroestimulación sacra. Consulte Video Resumen en http://links.lww.com/DCR/C192(Traducción-Dr. Jorge Silva Velazco ).

Pentecostal spirituality in the context of faith and hope gospel (prosperity preaching): African Pentecostal response to the COVID-19 pandemic.

Covid-19 has challenged humanity in several ways and has created the opportunity for reflection on our spirituality and the hope for divine healing of the world, while scientific communities do their best to find solutions to the pandemic from their perspective. In light of this, the article seeks to address issues of spirituality in the context of the COVID-19 pandemic and how the Pentecostal community is responding to this challenge through the preaching of faith and hope messages. The article addresses the issue of "prosperity preaching" from the perspective of the concept of faith and hope gospel. The article argues that the faith and hope messages of the Pentecostals are not only proclaimed as means of the spiritual sustainability of members but also for psychological/emotional stability. It also argues that although Pentecostals are doing their best in their religious and spiritual response to the pandemic, they should accommodate the application of the theology of the sovereignty of God in every situation and encourage their members to seek medical attention where applicable.

Measuring quality of life in people living with and beyond cancer in the UK.

PURPOSE: The aim of this study was to identify the most appropriate measure of quality of life (QoL) for patients living with and beyond cancer. METHODS: One hundred eighty-two people attending cancer clinics in Central London at various stages post-treatment, completed a series of QoL measures: FACT-G, EORTC QLQ-C30 , IOCv2 (positive and negative subscales) and WEMWBS, a wellbeing measure. These measures were chosen as the commonest measures used in previous research. Correlation tests were used to assess the association between scales. Participants were also asked about pertinence and ease of completion. RESULTS: There was a significant positive correlation between the four domain scores of the two health-related QoL measures (.32 ≤ r ≤ .72, P < .001), and a significant large negative correlation between these and the negative IOCv2 subscale scores (- .39 ≤ r ≤ - .63, P < .001). There was a significant moderate positive correlation between positive IOCv2 subscale and WEMWBS scores (r = .35, P < .001). However, neither the FACT-G nor the EORTC showed any significant correlation with the positive IOCv2 subscale. Participants rated all measures similarly with regards to pertinence and ease of use. CONCLUSION: There was little to choose between FACT-G, EORTC, and the negative IOC scales, any of which may be used to measure QoL. However, the two IOCv2 subscales capture unique aspects of QoL compared to the other measures. The IOCv2 can be used to identify those cancer survivors who would benefit from interventions to improve their QoL and to target specific needs thereby providing more holistic and personalised care beyond cancer treatment.

Supporting informed choice in acupuncture: effects of a new person-, evidence- and theory-based website for patients with back pain.

OBJECTIVES: To test whether a newly developed person-, theory- and evidence-based website about acupuncture helps patients make informed decisions about whether or not to use acupuncture for back pain. METHODS: A randomised online study compared a newly developed 'enhanced website' to a 'standard website'. The enhanced website provided evidence-based information in a person-based manner and targeted psychological constructs. The standard website was based on a widely used patient information leaflet. In total, 350 adults with recent self-reported back pain were recruited from general practices in South West England. The two primary outcomes were knowledge change and making an informed choice about using acupuncture. Secondary outcomes were beliefs about and willingness to have acupuncture. RESULTS: Participants who viewed the enhanced acupuncture website had a significantly greater increase in knowledge about acupuncture (M = 1.1, standard deviation (SD) = 1.7) than participants who viewed the standard website (M = 0.2, SD = 1.1; F(1, 315) = 37.93, p < 0.001, η2 = .107). Participants who viewed the enhanced acupuncture website were also 3.3 times more likely to make an informed choice about using acupuncture than those who viewed the standard website (χ2(1) = 23.46, p < 0.001). There were no significant effects on treatment beliefs or willingness to have acupuncture. CONCLUSION: The enhanced website improved patients' knowledge and ability to make an informed choice about acupuncture, but did not optimise treatment beliefs or change willingness to have acupuncture. The enhanced website could be used to support informed decision-making among primary care patients and members of the general public considering using acupuncture for back pain.

Topical vapocoolant spray reduces nociceptive response to ear notching in neonatal piglets.

OBJECTIVE: To evaluate the efficacy of a vapocoolant spray (VS) to provide local anaesthesia for piglets during ear notching. STUDY DESIGN: Randomized study. ANIMALS: Eleven 10 day old and forty 3-5 day old Large White piglets. METHODS: Temperature validation studies using thermocouples and a temperature data logger were conducted on dead and live tissue to determine optimal spray distance and duration to reduce tissue temperature to below 10 °C. A behavioural trial was conducted to assess efficacy for ear notching. Piglets were randomly assigned to one of four treatment groups: positive control (POS; n = 10), VS (n = 10), lignocaine (LIG; n = 10) and negative control (NEG; n = 10). Spray was administered to the margin of each ear, from a distance of 10 cm, and for a duration of 2 seconds immediately prior to ear notching. Behavioural observation was used to assess movement and vocal response, with responses categorized as no response (0) and response (1). RESULTS: Temperature and tissue validation studies indicated that a 2 second spray from 10 cm reduced tissue temperature to below 10 °C, and reduced response to stimulation of the skin with an 18 gauge needle (p < 0.001). There was a significant effect of treatment on response to ear notching (p < 0.001). The probability of a piglet to respond to ear notching was 98.7% for NEG piglets, compared with those treated with VS (5.3%), LIG (1.1%) and sham-notched piglets (0.9%). CONCLUSIONS AND CLINICAL RELEVANCE: This study contributes new data on the pain of ear notching in piglets. The application of a topical VS prior to ear notching reduced the antinociceptive response of piglets to the procedure, similar to that of a local anaesthetic. Cryoanaesthesia presents a simple and effective option for reducing the pain response to this simple husbandry procedure.

Review of systematic reviews of non-pharmacological interventions to improve quality of life in cancer survivors.

OBJECTIVES: Over two million people in the UK are living with and beyond cancer. A third report diminished quality of life. DESIGN: A review of published systematic reviews to identify effective non-pharmacological interventions to improve the quality of life of cancer survivors. DATA SOURCES: Databases searched until May 2017 included PubMed, Cochrane Central, EMBASE, MEDLINE, Web of Science, the Cumulative Index to Nursing and Allied Health Literature, and PsycINFO. STUDY SELECTION: Published systematic reviews of randomised trials of non-pharmacological interventions for people living with and beyond cancer were included; included reviews targeted patients aged over 18. All participants had already received a cancer diagnosis. Interventions located in any healthcare setting, home or online were included. Reviews of alternative therapies or those non-English reports were excluded. Two researchers independently assessed titles, abstracts and the full text of papers, and independently extracted the data. OUTCOMES: The primary outcome of interest was any measure of global (overall) quality of life. ANALYTICAL METHODS: Quality assessment assessing methdological quality of systematic reviews (AMSTAR) and narrative synthesis, evaluating effectiveness of non-pharmacological interventions and their components. RESULTS: Of 14 430 unique titles, 21 were included in the review of reviews. There was little overlap in the primary papers across these reviews. Thirteen reviews covered mixed tumour groups, seven focused on breast cancer and one focused on prostate cancer. Face-to-face interventions were often combined with online, telephone and paper-based reading materials. Interventions included physical, psychological or behavioural, multidimensional rehabilitation and online approaches. Yoga specifically, physical exercise more generally, cognitive behavioural therapy (CBT) and mindfulness-based stress reduction (MBSR) programmes showed benefit in terms of quality of life. CONCLUSIONS: Exercise-based interventions were effective in the short (less than 3-8 months) and long term. CBT and MBSR also showed benefits, especially in the short term. The evidence for multidisciplinary, online and educational interventions was equivocal.

Topical anaesthesia reduces sensitivity of castration wounds in neonatal piglets.

The aim of this study was to do determine the efficacy of the topical anaesthetic Tri-Solfen® in the amelioration of the pain of castration in piglets. The trial was conducted over a three day period, and blocked across six litters with 12 piglets treated on days one and two, and 16 on day three. The piglets were randomly allocated by weight and litter to 1 of 4 treatment groups: (i) sham castration (SHAM; n = 10); (ii) surgical castration with no anaesthetic intervention (CAST; n = 10); (iii) surgical castration with post-operative topical anaesthesia (TRI; n = 10); (iv) surgical castration with a pre-operative intra-testicular lignocaine hydrochloride injection (LIG; n = 10). Wound sensitivity testing involved von Frey monofilaments of weights 4g and 300g, and an 18 gauge needle, used to stimulate the wound and surrounding skin respectively, at various pre-determined sites. Neonatal piglets receiving topical anaesthesia (Tri-Solfen®) spray into castration wounds had significantly lower wound sensitivity responses for up to 4h, compared to those castrated following intra-testicular lignocaine injection or those with no treatment. The use of topical anaesthetic is suggested as a practical and affordable method of improving piglet welfare during castration.

Does kinesiology tape increase trunk forward flexion?

INTRODUCTION: Non specific lower back pain is a common musculoskeletal disorder in manual labourers due to the strenuous nature of their job. Fear of pain can cause restrictions in trunk movement leading to reduced flexibility. Kinesiology Tape (KT) may be an option for treating low back stiffness. The present study investigated the immediate effect of KT on trunk flexion active range of motion. METHOD: 34 male participants (mean age ± SD: 42 ± 11), in physically demanding jobs, asymptomatic of pain, with a history of non specific lower back pain were randomly assigned to: 1) KT Intervention (KTI) or 2) KT Placebo (KTP). Trunk flexion data was collected at baseline and immediately following tape application. ANCOVA was used to examine the differences between groups. RESULTS: The KTI group demonstrated a statistically significant gain in Trunk flexion compared with baseline (2.75 cm, P < 0.05). Changes from pre to post treatment for the KTP were not significant (1.57 cm, P = 0.062). No statistically significant differences existed between groups post-treatment (P = 0.218). CONCLUSION: KTI demonstrates an immediate positive effect on trunk flexion when compared with baseline measurements. However, results suggest that KTI performs no better than a comparable placebo.

Assessing knowledge about acupuncture: A survey of people with back pain in the UK.

OBJECTIVES: Despite the prevalence of acupuncture treatment in the UK, and the increasing evidence of safety and effectiveness, the information presented to patients by practitioners frequently contains inaccuracies. As knowledge of treatment affects both patient decision-making and treatment outcomes, this study aimed to establish what is known about acupuncture in a sample of people who had, and had not, previously experienced acupuncture. DESIGN: A 15-item questionnaire was constructed to assess knowledge of acupuncture. SETTING: Online survey of people with a history of back pain. RESULTS: 202 participants completed the questionnaire. 66.8% of the sample was female and 33.2% male, with a mean age of 35 years (range 18-74 years). 87.6% had back pain in the past six months, 44.1% currently. 21.8% had previously received acupuncture, and 69.8% had previously read or heard information about acupuncture. On average participants answered 11.03 of 15 questions about acupuncture correctly (SD=2.64). Items relating to common concerns about acupuncture, acupuncture efficacy, and types of acupuncture were correctly answered by ≥80% of participants. Participants possessed less knowledge of accessibility, Government legislation, and methods of administration. CONCLUSIONS: The study identified key gaps in knowledge about acupuncture among patients. In particular, many participants were unaware that acupuncture is available from the UK National Health Service and that acupuncturists are not subject to statutory regulation in the UK. These knowledge gaps should be addressed in order to increase people's understanding of and access to acupuncture.

Using psychological theory and qualitative methods to develop a new evidence-based website about acupuncture for back pain.

INTRODUCTION: Potential acupuncture patients seek out information about acupuncture from various sources including websites, many of which are unreliable. We aimed to create an informative, scientifically accurate and engaging website to educate patients about acupuncture for back pain and modify their beliefs in a way that might enhance its clinical effects. METHODS: We used psychological theory and techniques to design an evidence-based website, incorporating multimedia elements. We conducted qualitative "think aloud" audio-recorded interviews to elicit user views of the website. A convenience sample of ten participants (4 male; aged 21-64 years from the local community) looked at the website in the presence of a researcher and spoke their thoughts out loud. Comments were categorised by topic. RESULTS: The website comprises 11 main pages and addresses key topics of interest to potential acupuncture patients, including beneficial and adverse effects, mechanisms of action, safety, practicalities, and patients' experiences of acupuncture. It provides information through text, evidence summaries and audio-clips of four patients' stories and two acupuncturists' descriptions of their practice, and three short films. Evidence from the think aloud study was used to identify opportunities to make the website more informative, engaging, and user-friendly. CONCLUSIONS: Using a combination of psychological theory and qualitative interviews enabled us to produce a user-friendly, evidence-based website that is likely to change patients' beliefs about acupuncture for back pain. Before using the website in clinical settings it is necessary to test its effects on key outcomes including patients' beliefs and capacity for making informed choices about acupuncture.

A UK based review of recommendations regarding the management of chronic fatigue syndrome.

OBJECTIVES: Chronic fatigue syndrome (CFS) is a controversial illness, with apparent disagreements between medical authorities and patient support organisations regarding safe and effective treatments. The aim of this study was to measure the extent of different views regarding treatments, comparing patient support organisations and medical authorities in the UK. METHODS: Two independent raters analysed two groups of resources: UK patient support websites and both medical websites and textbooks. A 5-point Likert scale was developed with the question 'With what strength does the source recommend these treatments?' The various treatments were divided into the following four groups: complementary and alternative medicine (CAM), pharmacological, rehabilitative, and pacing therapies. RESULTS: There were significant differences between the scores for patient support organisations and medical sources for all 4 treatment groups. The results for supporting CAM were 74% (patient group) vs 16% (medical source) (p<0.001), 71% vs 42% for pharmacological (p=0.01), 28% vs 94% for rehabilitative (p<0.001) and 91% vs 50% for pacing treatments (p=0.001). CONCLUSIONS: There were substantially different treatment recommendations between patient support organisations and medical sources. Since expectations can determine response to treatment, these different views may reduce the engagement in and effectiveness of rehabilitative therapies recommended by national guidelines and supported by systematic reviews.

The discovery and development of sorafenib for the treatment of thyroid cancer.

INTRODUCTION: Although the prognosis for most differentiated thyroid cancers (DTCs) remains excellent, recurrence and insensitivity to radioactive iodine (RAI) lead to therapeutic challenges and poorer outcomes. In defining the pathogenesis of DTC, multiple genetic alterations have been identified in key pathways focused around receptor tyrosine kinases (RTKs) and the MAPK cascade. Sorafenib was specifically developed to target rapidly accelerated fibrosarcoma (RAF) kinase in the MAPK pathway. It has been shown, however, to have potent inhibition of several key RTKs, RAF kinase and the V600E BRAF mutation, gaining FDA approval in November 2013 for advanced RAI-refractory DTC. AREAS COVERED: The authors provide a review of the targeted RAF kinase discovery strategy as well as the preclinical and clinical development of sorafenib, leading to FDA approval of DTC. The authors also provide some insight into the clinical use of sorafenib and look at important considerations for treatment. EXPERT OPINION: Sorafenib significantly improves progression-free survival in metastatic DTC patients who are RAI-refractory. However, the overall survival benefit is still unproven and requires additional follow up. Despite its cost and significant side-effect profile, which results in dose reductions in the majority of DTC patients, sorafenib should be considered for the treatment of RAI-refractory advanced DTC patients following evaluation of their individual risk-benefit stratification.

The pre-reflective experience of "I" as a continuously existing being: the role of temporal functional binding.

The present moment is of infinitesimally brief duration. In the brain, however, there are perceptual processes that bind together events occurring at different times, on a time scale of milliseconds, into a coherent and integrated temporal representation. These processes include temporal integration, as in perception of biological motion, synchronisation, and change detection. These processes are also responsible for temporal integration and coherence in inner mental life, such as in mental imagery. I argue that this gives rise to the pre-reflective experience of the self as a continuously existing being. Temporal integration is also a feature of the experience of action-outcome relations, and I argue that this produces a pre-reflective experience of the self, not just as continuously existing, but also as the doer of both physical and mental actions. This is the foundation on which the idea of the self as continuously existing on longer time scales--the narrative self--is built.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling.

BACKGROUND: Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE: To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN: Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING: General population and genitourinary medicine clinic attenders. PARTICIPANTS: Heterosexual women and men. INTERVENTIONS: Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES: Population prevalence; index case reinfection; and partners treated per index case. RESULTS: Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, >10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS: There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

The experience of force: the role of haptic experience of forces in visual perception of object motion and interactions, mental simulation, and motion-related judgments.

Forces are experienced in actions on objects. The mechanoreceptor system is stimulated by proximal forces in interactions with objects, and experiences of force occur in a context of information yielded by other sensory modalities, principally vision. These experiences are registered and stored as episodic traces in the brain. These stored representations are involved in generating visual impressions of forces and causality in object motion and interactions. Kinematic information provided by vision is matched to kinematic features of stored representations, and the information about forces and causality in those representations then forms part of the perceptual interpretation. I apply this account to the perception of interactions between objects and to motions of objects that do not have perceived external causes, in which motion tends to be perceptually interpreted as biological or internally caused. I also apply it to internal simulations of events involving mental imagery, such as mental rotation, trajectory extrapolation and judgment, visual memory for the location of moving objects, and the learning of perceptual judgments and motor skills. Simulations support more accurate judgments when they represent the underlying dynamics of the event simulated. Mechanoreception gives us whatever limited ability we have to perceive interactions and object motions in terms of forces and resistances; it supports our practical interventions on objects by enabling us to generate simulations that are guided by inferences about forces and resistances, and it helps us learn novel, visually based judgments about object behavior.

Congenital chondrodystrophy of unknown origin in beef herds.

Congenital chondrodystrophy of unknown origin (CCUO), often referred to as 'acorn calf disease' or congenital joint laxity and dwarfism (CJLD), has been reported in beef cattle in Canada, the United States, Europe, South Africa, New Zealand and Australia. An association of CCUO with grazing drought-affected pastures, feeding hay-only or silage-only diets or supplementation with apple pulp suggests a nutritional cause such as a mineral deficiency. This review compares published reports on CCUO in order to identify common features among outbreaks and to provide a basis for future research into the condition. A protocol for investigation of outbreaks is provided to improve the outcome of future comparisons.

Cross-species absorption, metabolism, distribution and pharmacokinetics of BI 201335, a potent HCV genotype 1 NS3/4A protease inhibitor.

The present study describes the cross-species absorption, metabolism, distribution and pharmacokinetics of BI 201335, a potent HCV protease inhibitor currently in phase III clinical trials. BI 201335 showed a good Caco-II permeability (8.7 × 10(-6) cm/sec) and in vitro metabolic stability (predicted hepatic clearence (CL(hep)) <19% Q(h) in all species tested). Single dose PK revealed a clearance of 17, 3.0 and 2.6 mL/min/kg in rat, monkey and dog respectively, with a corresponding oral bioavailability of 29.1, 25.5 and 35.6%. Comparative plasma and liver PK profile in rodents showed a high liver Kp in the rat (42-fold), suggesting high target tissue distribution. Simple allometry based on animal PK predicted a human oral CL/F of 168 mL/min, within two-fold of the observed value (118 mL/min) at 240 mg in healthy volunteers. Allometry of volume of distribution generated a low exponent of 0.59, and a much lower predicted Vss/F (5-fold less than observed). Several different approaches of Vss/F prediction were evaluated and compared with the value observed in human. The averaged Vss/F from preclinical animals provides the best estimation of the observed human value (169 L vs. 175 L). Corresponding human "effective" t(1/2) values were also compared. The predicted human t(1/2) based on the CL from allometry with metabolic corrections and the averaged animal Vss represented the best estimation of the clinical data (12.1 vs. 17.2 hr). The present study demonstrated that the good preclinical ADMEPK profile of BI 201335 is consistent with that observed in the clinic. While preclinical data accurately predicted the human CL, the prediction of human Vss seems to be more challenging. The averaged Vss/F from all tested preclinical animals provided the best prediction of human Vss and the resulting "effective" t(1/2).

Practice, practitioner, or placebo? A multifactorial, mixed-methods randomized controlled trial of acupuncture.

The nonspecific effects of acupuncture are well documented; we wished to quantify these factors in osteoarthritic (OA) pain, examining needling, the consultation, and the practitioner. In a prospective randomised, single-blind, placebo-controlled, multifactorial, mixed-methods trial, 221 patients with OA awaiting joint replacement surgery were recruited. Interventions were acupuncture, Streitberger placebo acupuncture, and mock electrical stimulation, each with empathic or nonempathic consultations. Interventions involved eight 30-minute treatments over 4 weeks. The primary outcome was pain (VAS) at 1 week posttreatment. Face-to-face qualitative interviews were conducted (purposive sample, 27 participants). Improvements occurred from baseline for all interventions with no significant differences between real and placebo acupuncture (mean difference -2.7 mm, 95% confidence intervals -9.0 to 3.6; P=.40) or mock stimulation (-3.9, -10.4 to 2.7; P=.25). Empathic consultations did not affect pain (3.0mm, -2.2 to 8.2; P=.26) but practitioner 3 achieved greater analgesia than practitioner 2 (10.9, 3.9 to 18.0; P=.002). Qualitative analysis indicated that patients' beliefs about treatment veracity and confidence in outcomes were reciprocally linked. The supportive nature of the trial attenuated differences between the different consultation styles. Improvements occurred from baseline, but acupuncture has no specific efficacy over either placebo. The individual practitioner and the patient's belief had a significant effect on outcome. The 2 placebos were equally as effective and credible as acupuncture. Needle and nonneedle placebos are equivalent. An unknown characteristic of the treating practitioner predicts outcome, as does the patient's belief (independently). Beliefs about treatment veracity shape how patients self-report outcome, complicating and confounding study interpretation.

A biomechanical comparison of periprosthetic femoral fracture fixation in normal and osteoporotic cadaveric bone.

Several techniques are described for fixation of Vancouver B1 femoral shaft fractures after total hip arthroplasty. Twenty-four femurs were scanned by dual x-ray absorptiometry scanned and matched for bone mineral density. Femurs were implanted with a cemented simulated total hip prosthesis with a simulated periprosthetic femur fracture distal to the stem. Fractures were fixed with Synthes (Paoli, Pa) 12-hole curved plates and 4 different constructs proximally. Each construct was loaded to failure in axial compression. Constructs with locking and nonlocking screws demonstrated equivalent loads at failure and were superior in load at failure compared with cables. Cable constructs failed proximally. No proximal failures occurred in specimens fixed with screws and cables. A combination of locked or nonlocked screws and supplemental cable fixation is recommended for the treatment of Vancouver B1 periprosthetic femur fractures.

Forging convictions: the effects of active participation in a clinical trial.

This qualitative study explored non-specific influences on participation in, and outcomes of, a randomised controlled trial. It was nested within a single-blind clinical trial of western acupuncture which compared real acupuncture with two types of placebo control administered to National Health Service (NHS) patients awaiting hip and knee replacement surgery in England. Data collection (2004-2008) was based on narrative-style interviews and participant observation. The results indicate that trial recruitment and retention depend on a set of convictions forged largely as a result of contextual factors peripheral to the intervention, including the friendliness and helpfulness of research centre staff and status of the administering practitioner. These convictions also influence the reporting of the study outcomes, particularly if participants experience uncertainties when choosing an appropriate response. The findings suggest that participants in clinical trials are actively involved in shaping the research process, rather than passive recipients of treatment. Thus the outcomes of trials, notably those involving contact interventions, should be regarded not as matters of fact, but as products of complex environmental, social, interpretive and biological processes. In this paper, we develop and present a 'theory of active research participation' which offers a framework for understanding the impact of non-specific processes in clinical trials.