Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production.

Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of 79 unit recordings exhibited firing-rate modulation during a syllable reading task across 12 subjects (male and female). Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, whereas locking to speech onset was associated more with units that increased firing rate. These unique data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons.SIGNIFICANCE STATEMENT The basal ganglia are widely assumed to participate in speech production, yet no prior studies have reported detailed examination of speech-related activity in basal ganglia nuclei. Using microelectrode recordings from the subthalamic nucleus during a single-syllable reading task, in awake humans undergoing deep brain stimulation implantation surgery, we show that the firing rate of subthalamic nucleus neurons is modulated in response to motor execution aspects of speech. These results are the first to establish a role for subthalamic nucleus neurons in encoding of aspects of speech production, and they lay the groundwork for launching a modern subfield to explore basal ganglia function in human speech.

Genetic mapping of quantitative trait loci for tuber-cadmium and zinc concentration in potato reveals associations with maturity and both overlapping and independent components of genetic control.

KEY MESSAGE: Cd is a toxic metal, whilst Zn is an essential for plant and human health. Both can accumulate in potato tubers. We examine the genetic control of this process. The aim of this study was to map quantitative trait loci (QTLs) influencing tuber concentrations of cadmium (Cd) and zinc (Zn). We developed a segregating population comprising 188 F1 progeny derived from crossing two tetraploid cultivars exhibiting divergent tuber-Cd-accumulation phenotypes. These progeny were genotyped using the SolCap 8303 SNP array, and evaluated for Cd, Zn, and maturity-related traits. Linkage and QTL mapping were performed using TetraploidSNPMap software, which incorporates all allele dosage information. The final genetic map comprised 3755 SNP markers with average marker density of 2.94 per cM. Tuber-Cd and Zn concentrations were measured in the segregating population over 2 years. QTL mapping identified four loci for tuber-Cd concentration on chromosomes 3, 5, 6, and 7, which explained genetic variance ranging from 5 to 33%, and five loci for tuber-Zn concentration on chromosome 1, 3, 5, and, 6 explaining from 5 to 38% of genetic variance. Among the QTL identified for tuber-Cd concentration, three loci coincided with tuber-Zn concentration. The largest effect QTL for both tuber-Cd and Zn concentration coincided with the maturity locus on chromosome 5 where earliness was associated with increased tuber concentration of both metals. Coincident minor-effect QTL for Cd and Zn sharing the same direction of effect was also found on chromosomes 3 and 6, and these were unrelated to maturity The results indicate partially overlapping genetic control of tuber-Cd and Zn concentration in the cross, involving both maturity-related and non-maturity-related mechanisms.

Near infrared spectroscopy for body fat sensing in neonates: quantitative analysis by GAMOS simulations.

BACKGROUND: Under-nutrition in neonates is closely linked to low body fat percentage. Undernourished neonates are exposed to immediate mortality as well as unwanted health impacts in their later life including obesity and hypertension. One potential low cost approach for obtaining direct measurements of body fat is near-infrared (NIR) interactance. The aims of this study were to model the effect of varying volume fractions of melanin and water in skin over NIR spectra, and to define sensitivity of NIR reflection on changes of thickness of subcutaneous fat. GAMOS simulations were used to develop two single fat layer models and four complete skin models over a range of skin colour (only for four skin models) and hydration within a spectrum of 800-1100 nm. The thickness of the subcutaneous fat was set from 1 to 15 mm in 1 mm intervals in each model. RESULTS: Varying volume fractions of water in skin resulted minimal changes of NIR intensity at ranges of wavelengths from 890 to 940 nm and from 1010 to 1100 nm. Variation of the melanin volume in skin meanwhile was found to strongly influence the NIR intensity and sensitivity. The NIR sensitivities and NIR intensity over thickness of fat decreased from the Caucasian skin to African skin throughout the range of wavelengths. For the relationship between the NIR reflection and the thickness of subcutaneous fat, logarithmic relationship was obtained. CONCLUSIONS: The minimal changes of NIR intensity values at wavelengths within the ranges from 890 to 940 nm and from 1010 to 1100 nm to variation of volume fractions of water suggests that wavelengths within those two ranges are considered for use in measurement of body fat to solve the variation of hydration in neonates. The stronger influence of skin colour on NIR shows that the melanin effect needs to be corrected by an independent measurement or by a modeling approach. The logarithmic response obtained with higher sensitivity at the lower range of thickness of fat suggests that implementation of NIRS may be suited for detecting under-nutrition and monitoring nutritional interventions for malnutrition in neonates in resource-constrained communities.

Synthesis of novel 24-amino-25,26,27-trinorlanost-8-enes: cytotoxic and apoptotic potential in U937 cells.

In the present study, the synthesis of a range of novel 24-amino-25,26,27-trinorlanost-8-ene derivatives including 24-piperadino-trinorlanost-8-enes, 24-piperazino-trinorlanost-8-enes, 24-morpholino-trinorlanost-8-enes, and 24-diethylamino-trinorlanost-8-enes is reported and their cytotoxic and apoptotic potential evaluated in U937 cell lines. Excellent IC50 results for piperidine and 1-(2-hydroxyethyl)piperazine derivatives have been observed (IC50 values of 1.9 µM and 2.7 µM in U937 cells, respectively).

Why routine clinical follow-up for patients with early stage endometrial cancer is not always necessary: a study on women in South Wales.

OBJECTIVE: This study aimed to examine the existing methods of follow-up in women who have undergone treatment of early endometrial carcinoma in South Wales and to assess if they are appropriate. DESIGN: This study used a retrospective analysis of follow-up data. SETTING: This study was performed in the Virtual Gynaecological Oncology Centre, South Wales, United Kingdom. SAMPLE: This study sample is composed of 552 women. METHODS: Data regarding follow-up were collected retrospectively from patient case notes and computerized data systems. Data were analyzed using the Pearson χ test, Cox proportional hazard regression analysis, and Kaplan-Meier curves. MAIN OUTCOME MEASURES: This study aimed to determine whether routine follow-up was beneficial in detecting disease recurrence and whether outcome was influenced by routine follow-up. RESULTS: Between January 1, 2000, and December 31, 2010, 552 women were treated for early stage endometrial carcinoma. The 5-year survival was 81%, and the 5-year progression-free survival was 77%. Of these 552 women, 81 (15%) developed a disease recurrence; the majority (61/81 [75%]) recurred within 3 years. The median survival was 35 months compared with 47 months in patients who did not develop a recurrence. Of the 81 patients, 73 (90%) were symptomatic and only 5 patients were truly asymptomatic at follow-up. The most important and significant prognostic factor was "recurrent disease" with overall survival (hazard ratio, 2.20; P < 0.001; 95% confidence interval, 1.75-2.65) and progression-free survival (hazard ratio, 2.52; P < 0.001; 95% confidence interval, 2.09-2.95). "Asymptomatic recurrence" was not an independent predictor of outcome. CONCLUSIONS: Routine follow-up for early endometrial cancer is not beneficial for patients because most were symptomatic at the time of detection. It does not significantly improve the outcome. We propose altering the follow-up time regimen and adopting alternative follow-up strategies for women in South Wales.

Mosaic segmentation, COPD and CHF multimorbidity and hospital admission costs: a clinical linkage study.

BACKGROUND: How multimorbidity and socio-economic factors influence healthcare costs is unknown. Geo-demographic profiling system, Mosaic, which adds to socio-economic factors, provides the potential for an investigation of the relationship with multimorbidity, and their influence on healthcare costs. METHODS: Using chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) registers from 53 general practices for a population aged 40 years and over in Stoke-on-Trent, England (N = 10,113), were linked to hospital admissions data and Healthcare Resource Groups as a measure of hospital cost (2007-09). Eleven Mosaic groups were linked on the basis of individual patients' post codes. RESULTS: The COPD and CHF multimorbid group (n = 763) had the highest proportion with at least one hospital admission in the 3-year time period (n = 550, 72%), compared with the index COPD (56%) and CHF (66%) groups. Multimorbid patients had significantly higher mean costs for hospital admission (£4896) compared with the index COPD (£2769) or CHF (£3876). The associations between multimorbid groups and hospital admission costs compared with index groups varied by different Mosaic groups. CONCLUSIONS: CHF and COPD multimorbidity is associated with high costs, and average hospital admission costs vary by Mosaic segmentation. Multimorbidity and Mosaic provide an innovative basis for developing and targeting healthcare interventions in high-hospital-cost patients.

Pain medication management of musculoskeletal conditions at first presentation in primary care: analysis of routinely collected medical record data.

BACKGROUND: Primary care pharmacological management of new musculoskeletal conditions is not consistent, despite guidelines which recommend prescribing basic analgesics before higher potency medications such as opioids or non-steroidal inflammatory drugs (NSAIDs).The objective was to describe pharmacological management of new musculoskeletal conditions and determine patient characteristics associated with type of medication prescribed. METHODS: The study was set within a UK general practice database, the Consultations in Primary Care Archive (CiPCA). Patients aged 15 plus who had consulted for a musculoskeletal condition in 2006 but without a musculoskeletal consultation or analgesic prescription in the previous 12 months were identified from 12 general practices. Analgesic prescriptions within two weeks of first consultation were identified. The association of socio-demographic and clinical factors with receiving any analgesic prescription, and with strength of analgesic, were evaluated. RESULTS: 3236 patients consulted for a new musculoskeletal problem. 42% received a prescribed pain medication at that time. Of these, 47% were prescribed an NSAID, 24% basic analgesics, 18% moderate strength analgesics, and 11% strong analgesics. Increasing age was associated with an analgesic prescription but reduced likelihood of a prescription of NSAIDs or strong analgesics. Those in less deprived areas were less likely than those in the most deprived areas to be prescribed analgesics (odds ratio 0.69; 95% CI 0.55, 0.86). Those without comorbidity were more likely to be prescribed NSAIDs (relative risk ratios (RRR) compared to basic analgesics 1.89; 95% CI 0.96, 3.73). Prescribing of stronger analgesics was related to prior history of analgesic medication (for example, moderate analgesics RRR 1.88; 95% CI 1.11, 3.10). CONCLUSION: Over half of patients were not prescribed analgesia for a new episode of a musculoskeletal condition, but those that were often received NSAIDs. Analgesic choice appears multifactorial, but associations with age, comorbidity, and prior medication history suggest partial use of guidelines.

Logarithmic compression of sensory signals within the dendritic tree of a collision-sensitive neuron.

Neurons in a variety of species, both vertebrate and invertebrate, encode the kinematics of objects approaching on a collision course through a time-varying firing rate profile that initially increases, then peaks, and eventually decays as collision becomes imminent. In this temporal profile, the peak firing rate signals when the approaching object's subtended size reaches an angular threshold, an event which has been related to the timing of escape behaviors. In a locust neuron called the lobula giant motion detector (LGMD), the biophysical basis of this angular threshold computation relies on a multiplicative combination of the object's angular size and speed, achieved through a logarithmic-exponential transform. To understand how this transform is implemented, we modeled the encoding of angular velocity along the pathway leading to the LGMD based on the experimentally determined activation pattern of its presynaptic neurons. These simulations show that the logarithmic transform of angular speed occurs between the synaptic conductances activated by the approaching object onto the LGMD's dendritic tree and its membrane potential at the spike initiation zone. Thus, we demonstrate an example of how a single neuron's dendritic tree implements a mathematical step in a neural computation important for natural behavior.

Non-steroidal anti-inflammatory drugs and chronic kidney disease progression: a systematic review.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely regarded as one risk factor, which influences chronic kidney disease (CKD) progression. However, previous literature reviews have not quantified the risk in moderate to severe CKD patients. OBJECTIVE: To estimate the strength of association between chronic NSAID use and CKD progression. METHODS: We conducted a systematic review and meta-analysis of observational general practice or population studies featuring patients aged 45 years and over. The electronic databases searched were MEDLINE, EMBASE, Cochrane, AMED, BNI and CINAHL until September 2011 without date or language restrictions. Searches included the reference lists of relevant identified studies, WEB of KNOWLEDGE, openSIGLE, specific journals, the British Library and expert networks. For relevant studies, random effects meta-analysis was used to estimate the association between NSAID use and accelerated CKD progression (estimated glomerular filtration rate decline ≥ 15 ml/min/1.73 m2). RESULTS: From a possible 768 articles, after screening and selection, seven studies were identified (5 cohort, 1 case-control and 1 cross-sectional) and three were included in the meta-analysis. Regular-dose NSAID use did not significantly affect the risk of accelerated CKD progression; pooled odds ratio (OR) = 0.96 (95%CI: 0.86-1.07), but high-dose NSAID use significantly increased the risk of accelerated CKD progression; pooled OR = 1.26 (95%CI: 1.06-1.50). CONCLUSIONS: The avoidance of NSAIDs in the medium term is unnecessary in patients with moderate to severe CKD, if not otherwise contraindicated. As the definition of high-dose of NSAID use remains unclear, the lowest effective dose of NSAIDs should be prescribed where indicated.

Impact of neural noise on a sensory-motor pathway signaling impending collision.

Noise is a major concern in circuits processing electrical signals, including neural circuits. There are many factors that influence how noise propagates through neural circuits, and there are few systems in which noise levels have been studied throughout a processing pathway. We recorded intracellularly from multiple stages of a sensory-motor pathway in the locust that detects approaching objects. We found that responses are more variable and that signal-to-noise ratios (SNRs) are lower further from the sensory periphery. SNRs remain low even with the use of stimuli for which the pathway is most selective and for which the neuron representing its final sensory level must integrate many synaptic inputs. Modeling of this neuron shows that variability in the strength of individual synaptic inputs within a large population has little effect on the variability of the spiking output. In contrast, jitter in the timing of individual inputs and spontaneous variability is important for shaping the responses to preferred stimuli. These results suggest that neural noise is inherent to the processing of visual stimuli signaling impending collision and contributes to shaping neural responses along this sensory-motor pathway.

Inappropriate requesting of glycated hemoglobin (Hb A1c) is widespread: assessment of prevalence, impact of national guidance, and practice-to-practice variability.

BACKGROUND: Estimates suggest that approximately 25% of requests for pathology tests are unnecessary. Even in diabetes, for which international guidance provides recommended testing frequency, considerable variability in requesting practice exists. Using the diabetes marker, Hb A(1c), we examined (a) the prevalence of under- and overrequesting, (b) the impact of international guidance on prevalence, and (c) practice-to-practice variability. METHODS: We examined Hb A(1c) requests (519 664 requests from 115 730 patients, January 2001 to March 2011) processed by the Clinical Biochemistry Department, University Hospital of North Staffordshire, and prevalence of requesting outside guidance from intervals between requests was calculated. Requests were classified as "appropriate," "too soon," or "too late." We also assessed the effect of demographic factors and publication of guidance, along with between-practice variability, on prevalence. RESULTS: Only 49% of requests conformed to guidance; 21% were too soon and 30% were too late. Underrequesting was more common in primary care, in female patients, in younger patients, and in patients with generally poorer control (all P < 0.001); the reverse generally was true for overrequesting. Publication of guidance (e.g., American Diabetes Association, UK National Institute for Health and Clinical Excellence) had no significant impact on under- or overrequesting rates. Prevalence of inappropriate requests varied approximately 6-fold between general practices. CONCLUSIONS: Although overrequesting was common, underrequesting was more prevalent, potentially affecting longer-term health outcomes. National guidance appears to be an ineffective approach to changing request behavior, supporting the need for a multisystem approach to reducing variability.

Is the colposcopically directed punch biopsy a reliable diagnostic test in women with minor cytological lesions?

OBJECTIVE: The study aimed to determine the accuracy of the colposcopy-directed punch biopsy (punch) to detect or exclude high-grade cervical intraepithelial neoplasia (CIN 2 or 3) in women with atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (LSIL) cytological result and minor colposcopic findings. MATERIALS AND METHODS: In a diagnostic test accuracy study, women with ASCUS or LSIL cytological result and minor colposcopic changes had a single colposcopy-targeted punch biopsy was performed immediately followed by a loop electrocautery excision procedure (LEEP) biopsy. The trial was powered to detect a level of κ for a dichotomous outcome of 0.4 (i.e., fair-to-moderate agreement), with a two-sided significance level of 5% and a power of 90%. Accuracy parameters were computed using a cutoff for positive punch biopsy result of CIN 1+ and CIN 2+ for an outcome of CIN 2+ and CIN 3+ assessed in the LEEP specimen. RESULTS: Sixty-eight punch biopsy/LEEP-paired samples were analyzed. Of the 8 CIN 3 lesions, 6 and 4 were detected at cutoff CIN 1+ and CIN 2+, respectively (sensitivity, 50% and 75%). The corresponding specificities were 65% (39/60) and 97% (58/60). The punch biopsies identified only 14 (67%) or 6 (20%) of the 21 CIN 2+ lesions at cutoff CIN 1+ or CIN 2+, respectively. Of the punch biopsies, 31 (45.6%) accurately detected the severity of cervical abnormality. CONCLUSIONS: A single colposcopically directed punch biopsy appears to be insufficient to exclude underlying CIN 2 or 3.

Preliminary results of combining low frequency low intensity ultrasound and liposomal drug delivery to treat tumors in rats.

Ultrasound is a convenient trigger for site-specific drug delivery in cancer therapy. Nano-sized liposomes formulated from soy phosphatidyl choline, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] and alpha-tocopherol were loaded with Doxorubicin (Dox) using a pH gradient. The liposomal suspension was infused through the tail vein of BDIX rats possessing bilateral intradermal DHD/K12 tumors on their hind legs. Then 20-kHz ultrasound was applied to only one of the tumors for 15 minutes. This therapy was repeated weekly for 4 weeks. The results showed that in five of six rats, the tumors regressed to non-measurable size within 4 weeks. A paired comparison of the normalized size of the insonated and non-insonated tumors in the same rat indicated that the insonated tumors were smaller (p < 0.0001, n = 6 rats, 21 pairs). This observation has significant potential for non-invasive site-specific therapy of solid tumors.

Manifold parametrizations by eigenfunctions of the Laplacian and heat kernels.

We use heat kernels or eigenfunctions of the Laplacian to construct local coordinates on large classes of Euclidean domains and Riemannian manifolds (not necessarily smooth, e.g., with (alpha) metric). These coordinates are bi-Lipschitz on large neighborhoods of the domain or manifold, with constants controlling the distortion and the size of the neighborhoods that depend only on natural geometric properties of the domain or manifold. The proof of these results relies on novel estimates, from above and below, for the heat kernel and its gradient, as well as for the eigenfunctions of the Laplacian and their gradient, that hold in the non-smooth category, and are stable with respect to perturbations within this category. Finally, these coordinate systems are intrinsic and efficiently computable, and are of value in applications.

Is gynaecological surgical training a cause for concern?: a questionnaire survey of trainees and trainers.

BACKGROUND: Concerns have been raised as to whether the current postgraduate training programme for gynaecological surgery is being detrimentally affected by changes in working practices, in particular the European Working Time Directive (EWTD). The purpose of this study was to investigate the surgical activity of obstetrics and gynaecology trainees and to explore trainees' and trainers' opinions on the current barriers and potential solutions to surgical training. METHODS: Two questionnaire surveys were conducted, one to obstetrics and gynaecology trainees working within the West Midlands Deanery and a second to consultant gynaecologists in the West Midlands region. RESULTS: One hundred and four trainees (64.3%) and 66 consultant gynaecologists (55.0%) responded. Sixty-six trainees (66.7%) reported attending up to one operating list per week. However, 28.1% reported attending up to one list every two weeks or less and 5 trainees stated that they had not attended a list at all over the preceding 8 weeks. Trainees working in a unit with less than 3999 deliveries attended significantly more theatre sessions compared to trainees in units with over 4000 deliveries (p = 0.007), as did senior trainees (p = 0.032) and trainees attached to consultants performing major gynaecological surgery (p = 0.022). In the previous 8 weeks, only 6 trainees reported performing a total abdominal hysterectomy independently, all were senior trainees (ST6 and above). In the trainers' survey, only two respondents (3.0%) agreed that the current program produces doctors competent in general gynaecological surgery by the end of training, compared to 48 (73.8%) respondents who disagreed. CONCLUSIONS: Trainees' concerns over a lack of surgical training appear to be justified. The main barriers to training are perceived to be a lack of team structure and a lack of theatre time.

Indication and outcome of repeat large loop excision biopsies of the cervix.

INTRODUCTION: To investigate the indications for performing a second large loop excision of the transformation zone (LLETZ) biopsy and to compare the associated colposcopic and pathological findings and treatment morbidity compared with 1 LLETZ. METHODS: This is a case-control study that reviewed case notes and histology reports on women who had undergone 1 LLETZ biopsy (control group) and women who had undergone 2 biopsies (index group). A comparison of referral cytology, colposcopic findings, and pathological and clinical outcomes was performed. RESULTS: Of the women who went on to have 2 LLETZ biopsies, 88% had histologically proven high-grade cervical intraepithelial neoplasia (CIN) or invasion on their first biopsy. A significantly greater proportion of high-grade cytologic and histologic diagnoses were associated with the first LLETZ compared with the second LLETZ biopsy, 76.5% and 69.1% versus 39.5% and 30.9%, respectively. A significantly greater proportion of women in the control group were referred with low-grade cytology (28.0%) and were diagnosed with human papillomavirus/low-grade CIN on histology (31.7%) compared with the first cytologic and LLETZ results in the index group, 9.9% and 8.6%, respectively. Complications were low in both groups; the immediate complication rate was 4% after the first LLETZ compared with 1% after the second LLETZ. CONCLUSIONS: Most second LLETZ biopsies are performed in women with a history of biopsy-proven high-grade CIN and are not associated with an increased risk of immediate complications.

Development of diagnostic markers for use in breeding potatoes resistant to Globodera pallida pathotype Pa2/3 using germplasm derived from Solanum tuberosum ssp. andigena CPC 2802.

Quantitative resistance to Globodera pallida pathotype Pa2/3, originally derived from Solanum tuberosum ssp. andigena Commonwealth Potato Collection (CPC) accession 2802, is present in several potato cultivars and advanced breeding lines. One genetic component of this resistance, a large effect quantitative trait locus (QTL) on linkage group IV (which we have renamed GpaIV(adg)(s)) has previously been mapped in the tetraploid breeding line 12601ab1. In this study, we show that GpaIV(adg)(s) is also present in a breeding line called C1992/31 via genetic mapping in an F(1) population produced by crossing C1992/31 with the G. pallida susceptible cultivar Record. C1992/31 is relatively divergent from 12601ab1, confirming that GpaIV(adg)(s) is an ideal target for marker-assisted selection in currently available germplasm. To generate markers exhibiting diagnostic potential for GpaIV(adg)(s), three bacterial artificial chromosome clones were isolated from the QTL region, sequenced, and used to develop 15 primer sets generating single-copy amplicons, which were examined for polymorphisms exhibiting linkage to GpaIV(adg)(s) in C1992/31. Eight such polymorphisms were found. Subsequently, one insertion/deletion polymorphism, three single nucleotide polymorphisms and a specific allele of the microsatellite marker STM3016 were shown to exhibit diagnostic potential for the QTL in a panel of 37 potato genotypes, 12 with and 25 without accession CPC2082 in their pedigrees. STM3016 and one of the SNP polymorphisms, C237(119), were assayed in 178 potato genotypes, arising from crosses between C1992/31 and 16 G. pallida susceptible genotypes, undergoing selection in a commercial breeding programme. The results suggest that the diagnostic markers would most effectively be employed in MAS-based approaches to pyramid different resistance loci to develop cultivars exhibiting strong, durable resistance to G. pallida pathotype Pa2/3.

The British Gynaecological Cancer Society Delphi consultation exercise on expected standards of practice for doctors specializing in the area of gynecological oncology.

OBJECTIVE: To determine a set of auditable standards applicable to physicians working in the area of gynecological oncology, which could be implemented as accreditation criteria for the revalidation procedure. DESIGN: A 3-round Delphi consultation exercise. SETTING: British Gynaecological Cancer Society (BGCS) members and delegates at the 2006 and 2007 Annual BGCS conferences Population 35 BGCS members, 72 delegates attending the 2006 BGCS conference and 120 delegates attending the 2007 conference. METHODS: A preliminary Delphi consultation of members was performed electronically to determine the contents of the final Delphi questionnaires. Prioritization was achieved by scoring each parameter on a 5-point Likert scale. MAIN OUTCOME MEASURE: The mean score awarded to each benchmarking parameter and the identification of parameters scoring 4 or above 75% or more of the respondents. RESULTS: The first round contained responses from 68 participants in stage 1 and 72 in stage 2. The second round included 120 participants. Nine of the auditable standards in first round and 10 in the second round achieved a score of 4 or above 75% or more of the participants and were therefore considered to be essential for revalidation. The selected criteria focused on an individual clinician's caseload and performance, multidisciplinary team working and continued professional development. CONCLUSIONS: This study has used the Delphi technique to identify auditable standards which could be used in the revalidation process of physicians working in the area of gynecological cancer.

Frequency of nocturnal hypoxia in clinically stable patients during stroke rehabilitation.

OBJECTIVE: Sleep disordered breathing is common in patients with cerebrovascular disease. Nocturnal hypoxia may lead to daytime tiredness and cognitive impairment, thus affecting progress. This study assessed the prevalence of nocturnal hypoxia during rehabilitation from stroke. DESIGN: Prospective observational trial. SETTING: The stroke rehabilitation wards of the North Staffordshire Hospital, UK and of Kreiskrankenhaus Grevenbroich, Germany. SUBJECTS: Adult patients on a stroke rehabilitation ward, 10 days to 3 months (mean 32 days, SD18) after stroke onset (n = 160). Age and local environment-matched controls (n = 156) without a history of stroke were recruited from the community at both centres. MAIN MEASURES: Pulse oximetry was performed overnight on the day of enrolment from 21:00 to 09:00. The baseline awake oxygen saturation, the mean nocturnal oxygen saturation, the lowest nocturnal oxygen saturation and the 4% Oxygen Desaturation Index were calculated for each participant. RESULTS: The mean baseline awake oxygen saturation of stroke patients was at 95.3% (SD 1.7), 0.5% lower than that of controls (P = 0.005, independent t-test). The group means of the mean nocturnal oxygen saturation for stroke patients were 0.5% lower (at 93.8% SD 2.2) than controls (P = 0.03, independent t-test). The mean lowest nocturnal oxygen saturation was at 79.4% (SD 9.9), 5.9% lower than that of the controls (P<0.001, independent t-test). Considerably more stroke patients (n = 67, 42%) than controls (n = 24, 15%) had > or =10 desaturations below the baseline per hour (P<0.001 chi-square test). CONCLUSION: Clinically stable stroke patients enrolled in rehabilitation programmes have lower oxygen saturation and more nocturnal desaturations than non-stroke controls.

Current views and practices in the management of low-grade cervical abnormalities-results of a British Society for Colposcopy and Cervical Pathology Study.

OBJECTIVE: To determine current views and practice of the management of low-grade cervical abnormalities. MATERIALS AND METHODS: A questionnaire survey was distributed to all accredited colposcopists whose details were available on the British Society for Colposcopy and Cervical Pathology database. RESULTS: Of the 1292 colposcopists contacted, 470 responded to the questionnaire. Of these respondents, 57% were obstetricians/gynecologists, 16% were nurse colposcopists, and 12% were gynecological oncologists. Most colposcopists would only advise a woman to undergo treatment of low-grade cytology (atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion) with low-grade colposcopic findings if the disease was persistent for 24 months or more. There was significant diversity in the management between colposcopists working in different medical specialties. Gynecological oncologists and nurse colposcopists were less likely to be influenced by poor compliance (p <.01) or immunosuppression (p <.01) into offering treatment earlier for low-grade disease. Also, community gynecologists were more likely to routinely offer ablative treatment of low-grade disease compared with colposcopists based on secondary care, p <.01. CONCLUSIONS: The need for conservative management with low-grade cervical abnormalities and the accurate diagnosis of disease progression seem to be well understood. The reported management of low-grade cervical abnormalities seem to follow the National Health Service Cervical Screening Programme guidelines; however, there is diversity in practice between colposcopists working in different medical specialties.