Oscillatory entrainment to our early social or physical environment and the emergence of volitional control.

An individual's early interactions with their environment are thought to be largely passive; through the early years, the capacity for volitional control develops. Here, we consider: how is the emergence of volitional control characterised by changes in the entrainment observed between internal activity (behaviour, physiology and brain activity) and the sights and sounds in our everyday environment (physical and social)? We differentiate between contingent responsiveness (entrainment driven by evoked responses to external events) and oscillatory entrainment (driven by internal oscillators becoming temporally aligned with external oscillators). We conclude that ample evidence suggests that children show behavioural, physiological and neural entrainment to their physical and social environment, irrespective of volitional attention control; however, evidence for oscillatory entrainment beyond contingent responsiveness is currently lacking. Evidence for how oscillatory entrainment changes over developmental time is also lacking. Finally, we suggest a mechanism through which periodic environmental rhythms might facilitate both sensory processing and the development of volitional control even in the absence of oscillatory entrainment.

The phenomenology of auditory verbal hallucinations in emotionally unstable personality disorder and post-traumatic stress disorder.

OBJECTIVE: To explore the phenomenology of auditory verbal hallucinations (AVHs) in a clinical sample of young people who have a 'non-psychotic' diagnosis. METHODS: Ten participants aged 17-31 years with presentation of emotionally unstable personality disorder or post-traumatic stress disorder and frequent AVHs were recruited and participated in a qualitative study exploring their subjective experience of hearing voices. Photo-elicitation and ethnographic diaries were used to stimulate discussion in an otherwise unstructured walking interview. RESULTS: 'Non-psychotic' voices comprised auditory qualities such as volume and clarity. Participants commonly personified their voices, viewing them as distinct characters with which they could interact and form relationships. There appeared to be an intimate and unstable relationship between participant and voice, whereby voices changed according to the participants' mood, insecurities, distress and circumstance. Equally, participants reacted to provocation by the voice, leading to changes in mood and circumstance through emotional and physical disturbances. In contrast to our previous qualitative work in psychosis, voice hearing was not experienced with a sense of imposition or control. CONCLUSIONS: This phenomenological research yielded in-depth and novel accounts of 'non-psychotic' voices which were intimately linked to emotional experience. In contrast to standard reports of voices in disorders such as schizophrenia, participants described a complex and bi-directional relationship with their voices. Many other features were in common with voice hearing in psychosis. Knowledge of the phenomenology of hallucinations in non-psychotic disorders has the potential to inform future more successful management strategies. This report gives preliminary evidence for future research.

B Chromosome Diversity and Repetitive Sequence Distribution in an Isolated Population of Akodon montensis (Rodentia, Sigmodontinae).

B chromosomes are supernumerary chromosomes found in the karyotypes of approximately 15% of all eukaryotic species. They present parasitic behavior and do not follow the standard Mendelian pattern of inheritance, resulting in an imbalance in gametogenesis. The evolutionary dynamics of B chromosomes is still unknown for many species, but studies indicate that the accumulation of repetitive sequences plays an important role in the differentiation of these elements. We analyzed morphology, frequency, and possible homologies amongst different B chromosomes found in an isolated Akodon montensis population in southern Brazil. Repetitive sequences (18S, 5S rDNA and telomeric sequences) were used to test for their accumulation on the supernumerary chromosomes and describe their localization in the species. The results indicate 4 different B chromosome morphotypes, and DNA libraries were generated for 3 of them. 18S rDNA was labelled polymorphically, except in the B chromosomes, whereas the 5S rDNA was located exclusively in an interstitial position on the long arm of chromosome 5. Chromosome painting with the B probes based on FISH revealed a homologous composition for all B chromosome morphotypes and no homology with the chromosomes in the A complement. B chromosomes found in this population may have a common origin and subsequently diversified in size and morphology.

The relationship between epileptiform discharges and background activity in the visual analysis of electroencephalographic examinations in dogs with seizures of different etiologies.

Electroencephalographic (EEG) recordings in 125 outpatient dogs with various epileptiform encephalopathies were acquired under medetomidine sedation using subdermal wire electrodes. The features of canine EEG (background activity [BGA] and epileptiform discharges [EDs]) were assessed, described and compared. The dogs included neurologically healthy controls (N, n = 19), dogs with portosystemic shunt (PSS, n = 9), dogs with intracranial pathologies (IP, n = 27) and dogs with idiopathic epilepsy (IE, n = 70). A visual EEG analysis revealed significantly more pronounced high voltage, low-frequency BGA in the PSS and IP groups in comparison to the N and IE groups (PSS vs. N, PSS vs. IE P <0.0001; IP vs. N, IP vs. IE P = 0.043). At least one ED in the recording was found in 47.37% (n = 9/19) of the individuals in the N group, 88.9% (n = 8/9) of the dogs in the PSS group, 77.78% (n = 21/27) of the dogs in the IP group and 61.43% (n = 43/70) of the dogs in the IE group. The presence of bilateral symmetric triphasic (BST) waves was significantly higher in the PSS group than in the remaining groups. There was a strong prevalence of spike-waves in dogs with idiopathic epilepsy and of BST waves in dogs with portosystemic shunt. None of the dogs in group N had spike-waves or BST activity. EDs were observed more frequently in high and very high voltage, low frequency BGA than in low voltage, high frequency BGA.

Tolerability of up to 200 days of prophylaxis with valganciclovir oral solution and/or film-coated tablets in pediatric kidney transplant recipients at risk of cytomegalovirus disease.

This multicenter, open-label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty-six patients aged 4 months to 16 years received once-daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21.4%). There were fewer AEs during days 101-228 vs days 1-100. Twenty-seven patients (48.2%) had treatment-related AEs during valganciclovir treatment, most commonly leukopenia (21.4%), neutropenia (19.6%), anemia (7.1%), and tremor (5.4%). Treatment-related serious AEs were reported for nine patients (16.1%) and six withdrew due to AEs. Viremia was centrally confirmed in 10 patients; there was no confirmed CMV disease. One patient tested positive for a resistance mutation (UL97 L595F). Biopsy-proven acute rejection occurred in six patients (10.7%), but no graft loss or deaths occurred. In conclusion, up to 200 days of valganciclovir prophylaxis in pediatric kidney allograft recipients showed a safety profile consistent with that established in adult transplant patients.

Understanding auditory verbal hallucinations: a systematic review of current evidence.

OBJECTIVE: Auditory verbal hallucinations (AVHs) are core features of psychotic illness and remain significant in predicting poor outcome and risk. There has been a wide range of approaches to understanding these experiences. METHOD: A systematic literature review summarizing different methods of investigation and their results; phenomenology, descriptive psychopathology, psychological, cognitive neurobiology, and neuroimaging. RESULTS: A number of 764 papers and texts were screened and 113 reviewed. Phenomenological studies are comparably few in number, and psychopathology remains based on concepts defined in the early 20th century. Psychological models focus on voice content and emotional reaction, and suggest a continuum of AVHs from normal experience. Neuropsychological models include AVHs as misattribution of inner speech, whilst functional neuroimaging studies focus on the spontaneous activity and connectivity of auditory networks. CONCLUSION: There has been a large growth in research on AVHs in recent decades dominated by neurobiological and neuroimaging studies. Future research should include focus on phenomenological aspects and AVHs change over the course of developing illness. Integration between branches of enquiry is needed, and the risk is that without this, models are proposed and investigated that bear scant relevance to the symptom itself.

Traumeel S in preventing and treating mucositis in young patients undergoing SCT: a report of the Children's Oncology Group.

Mucositis can be a serious complication of hematopoietic SCT (HSCT). A previous phase II trial in 32 children undergoing HSCT reported a beneficial effect of the homeopathic remedy Traumeel S. The Children's Oncology Group sought to replicate the results in a multi-institutional trial. The study was an international multi-center, double-blind, randomized trial comparing Traumeel with placebo in patients aged 3-25 years undergoing myeloablative HSCT. Traumeel/placebo was started on Day -1 as a five-time daily mouth rinse. Efficacy of the treatment was assessed using the modified Walsh scale for mucositis, scored daily from Day -1 to 20 days after HCST. The main outcome was the sum of Walsh scale scores (area-under-the-curve (AUC)) over this period. Other outcomes included narcotic use, days of total parenteral feeding, days of nasogastric feeding and adverse events. In 181 evaluable patients, there was no statistical difference in mucositis (AUC) in the Traumeel group (76.7) compared with placebo (67.3) (P=0.13). There was a trend towards less narcotic usage in the Traumeel patients. No statistically beneficial effect from Traumeel was demonstrated for mucositis. We could not confirm that Traumeel is an effective treatment for mucositis in children undergoing HSCT.

Incidence rates for thromboembolic, bleeding and hepatic outcomes in patients undergoing hip or knee replacement surgery.

BACKGROUND: Data on clinical outcomes of patients in the general population undergoing knee replacement or hip replacement surgery are sparse. OBJECTIVES: To conduct an observational study using insurance claims data to assess the incidence of selected clinical events following knee replacement or hip replacement surgery in the USA. PATIENTS/METHODS: A total of 97,469 knee replacement patients and a total of 45,203 hip replacement patients were included during the period 2004-2008; the median age was 64 years, and 63% of knee replacement patients and 55% of hip replacement patients were women. RESULTS: During a median follow-up of 70-71 days, the incidence rates in knee replacement patients and hip replacement patients were, respectively: ischemic stroke, 15 and 19 per 1000 person-years; acute coronary syndrome (ACS), 15 and 18 per 1000 person-years; bleeding events, 46 and 47 per 1000 person-years; venous thromboembolism (VTE), 64 and 45 per 1000 person-years; and hepatic events, one and one per 1000 person-years. Approximately 45% of knee replacement and hip replacement patients had no claims for outpatient anticoagulant therapy within 1 week after discharge from hospital. CONCLUSIONS: Ischemic events such as stroke, ACS and VTE are important adverse events following knee replacement and hip replacement surgery. The results reported here can help in making challenging decisions regarding the clinical management of risks attributable to bleeding events and clotting events.

Why members of the public self-test: an interview study.

BACKGROUND: A wide range of self-tests are available where contact with a health professional is not necessary. OBJECTIVE: To investigate factors that influenced members of the public to use self-tests. METHODS: Questionnaires, sent to 2335 adults from two general practices in North Birmingham, asked whether recipients had used self-tests and sought consent for contacting them about taking part in an interview. Twenty-three people were interviewed, 20 of whom had used self-tests. The interviews were transcribed verbatim, and a thematic analysis was conducted. RESULTS: The findings were organized around two themes. 'Motivations for self-testing' describes the motivating factors surrounding participants' choices to use self-tests. This appeared to be influenced by a number of factors that were organized into four sub-themes: 'diagnosis or speculation', 'perceived benefits of self-testing', 'general attitudes to and experiences of health care' and 'general attitudes to health'. The second theme called 'experience of self-testing' describes participants' access to, and use of self-tests, and is split into three sub-themes: 'opportunistic awareness and access', 'use and application' and 'impact on life'. CONCLUSIONS: Overall, self-testing encompasses a broad variety of beliefs and experiences. Some participants saw self-tests as a serious diagnostic tool, whereas others used them out of simple curiosity. Some were motivated by their generally positive attitude to health, but others may have been motivated by negative health care experiences. Some saw self-testing as an empowering process to be proud of, while others seemed to view it as an illegitimate activity that needed to be hidden from professionals.

The efficacy and safety of 200 days valganciclovir cytomegalovirus prophylaxis in high-risk kidney transplant recipients.

Late-onset cytomegalovirus (CMV) disease is a significant problem with a standard 3-month prophylaxis regimen. This multicentre, double-blind, randomized controlled trial compared the efficacy and safety of 200 days' versus 100 days' valganciclovir prophylaxis (900 mg once daily) in 326 high-risk (D+/R-) kidney allograft recipients. Significantly fewer patients in the 200-day group versus the 100-day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200-day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy-proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild-to-moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days' prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5.

Healthcare workers' perceptions of the duty to work during an influenza pandemic.

Healthcare workers (HCWs) are often assumed to have a duty to work, even if faced with personal risk. This is particularly so for professionals (doctors and nurses). However, the health service also depends on non-professionals, such as porters, cooks and cleaners. The duty to work is currently under scrutiny because of the ongoing challenge of responding to pandemic influenza, where an effective response depends on most uninfected HCWs continuing to work, despite personal risk. This paper reports findings of a survey of HCWs (n = 1032) conducted across three National Health Service trusts in the West Midlands, UK, to establish whether HCWs' likelihood of working during a pandemic is associated with views about the duty to work. The sense that HCWs felt that they had a duty to work despite personal risk emerged strongly regardless of professional status. Besides a strong sense that everyone should pull together, all kinds of HCWs recognised a duty to work even in difficult circumstances, which correlated strongly with their stated likelihood of working. This suggests that HCWs' decisions about whether or not they are prepared to work during a pandemic are closely linked to their sense of duty. However, respondents' sense of the duty to work may conflict with their sense of duty to family, as well as other factors such as a perceived lack of reciprocity from their employers. Interestingly, nearly 25% of doctors did not consider that they had a duty to work where doing so would pose risks to themselves or their families.

Pharmacokinetics of oral valganciclovir solution and intravenous ganciclovir in pediatric renal and liver transplant recipients.

In an open-label, prospective, pharmacokinetic assessment, we evaluated total drug exposure (area under the curve [AUC]) of intravenous (IV) ganciclovir (GCV) and oral (p.o.) valganciclovir when normalized for body surface area (BSA) in pediatric liver (n=20) and renal (n=26) transplant patients Reference doses for IV GCV (200 mg/m(2)) and p.o. valganciclovir (520 mg/m(2)) were based on adult doses, and adjusted for BSA initially, and BSA and renal function (estimated via creatinine clearance [CrCL]) thereafter. Renal transplant patients received GCV on days 1-2, valganciclovir 260 mg/m(2) on day 3, and valganciclovir 520 mg/m(2) on day 4. Liver transplant patients received twice daily GCV from enrollment to day 12, and then valganciclovir twice daily on days 13-14. GCV pharmacokinetics were described using a population pharmacokinetic approach. Type of solid organ transplant (kidney or liver) had no effect on GCV pharmacokinetics. Median GCV exposure following valganciclovir 520 mg/m(2) was similar to that with IV GCV, and to that reported in adults. Patients <5 years of age had AUC values approximately 50% of those compared with older age ranges; dosing based on both BSA and CrCL increased drug exposure in younger patients. A dosing algorithm based on BSA and CrCL should be tested in future studies.

Valganciclovir dosing according to body surface area and renal function in pediatric solid organ transplant recipients.

Oral valganciclovir is effective prophylaxis for cytomegalovirus (CMV) disease in adults receiving solid organ transplantation (SOT). However, data in pediatrics are limited. This study evaluated the pharmacokinetics and safety of valganciclovir oral solution or tablets in 63 pediatric SOT recipients at risk of CMV disease, including 17 recipients < or =2 years old. Patients received up to 100 days' valganciclovir prophylaxis; dosage was calculated using the algorithm: dose (mg) = 7 x body surface area x creatinine clearance (Schwartz method; CrCLS). Ganciclovir pharmacokinetics were described using a population pharmacokinetic approach. Safety endpoints were measured up to week 26. Mean estimated ganciclovir exposures showed no clear relationship to either body size or renal function, indicating that the dosing algorithm adequately accounted for both these variables. Mean ganciclovir exposures, across age groups and organ recipient groups were: kidney 51.8 +/- 11.9 microg * h/mL; liver 61.7 +/- 29.5 microg * h/mL; heart 58.0 +/- 21.8 microg * h/mL. Treatment was well tolerated, with a safety profile similar to that in adults. Seven serious treatment-related adverse events (AEs) occurred in five patients. Two patients had CMV viremia during treatment but none experienced CMV disease. In conclusion, a valganciclovir-dosing algorithm that adjusted for body surface area and renal function provides ganciclovir exposures similar to those established as safe and effective in adults.

New measurement of the K+-->pi+ nunu branching ratio.

Three events for the decay K+-->pi+ nunu have been observed in the pion momentum region below the K+-->pi+pi0 peak, 140 < Ppi < 199 MeV/c, with an estimated background of 0.93+/-0.17(stat.) -0.24+0.32(syst.) events. Combining this observation with previously reported results yields a branching ratio of B(K+-->pi+ nunu) = (1.73(-1.05)+1.15) x 10(-10) consistent with the standard model prediction.

MR imaging-compatible electroencephalography electrode system for an epilepsy monitoring unit.

We studied the usefulness of an MR imaging-compatible electroencephalography (EEG) electrode system for continuous EEG recordings in our epilepsy monitoring unit (EMU) by comparing 100 consecutive patients with MR imaging-compatible and MR imaging-incompatible EEG recording electrodes who underwent MR imaging between 3:00 pm and 7:00 am. The MR imaging-compatible system captured seizures in 21/50 (42%) patients and clinically valuable new electrographic data in 13/50 (26%) patients during the study interval, whereas possible seizures were lost to recording in 19/50 (38%) patients in the MR imaging-incompatible system. EEG recording was comparable by both systems, but the nurses could disconnect and reconnect the patients to their electrode cables only in the MR imaging-compatible system during the study interval while the EEG technologists were off duty. This study shows that the MR imaging-compatible system could be used routinely for long-term monitoring of the patients in EMUs.

Medical education and patients' responsibilities: back to the future?

Medical student learning is dependent on an unwritten agreement between patients and the medical profession, in which students "practise" upon real patients in order that, when they are doctors, those same patients will benefit from the doctors' skills. Given the increasing propensity for patients to refuse to take part in such learning, there is a danger that doctors will qualify without being truly competent. As patients, we must all ask ourselves, when asked to take part in medical teaching: if this student/trainee doesn't learn now, on me and under supervision, how will the person be truly competent next time, when this is for real, and the patient might be me or my loved one? We argue that a new and more explicit agreement is needed, in which the default should be that all patients are willing to help in the education of medical students, while we ensure that all such students are already competent in simulation before first practising upon real patients.