Optimisation of the timing of fertilisation assessment for oocytes cultured in standard incubation: lessons learnt from time-lapse imaging of 78 348 embryos.

STUDY QUESTION: Using time-lapse data, can the current consensus for the timing of fertilisation assessment of oocytes, cultured in standard incubation, be optimised? SUMMARY ANSWER: The optimum time to perform fertilisation assessment for oocytes cultured in standard incubation is 16.5 ± 0.5 h post-insemination (hpi), and the current consensus requires modification in order to minimise the chance of fertilisation being missed. WHAT IS KNOWN ALREADY: Time-lapse incubation allows the embryologist to retrospectively review collated images of oocytes and embryos to capture important embryological observations that may otherwise be missed in standard incubation. According to expert consensus, the optimum time to perform the assessment of fertilisation is 17 ± 1 hpi. STUDY DESIGN, SIZE, DURATION: A retrospective, multicentre analysis utilised data obtained from 54 746 ICSI-derived embryos and 23 602 IVF-derived embryos cultured in time-lapse incubation between January 2011 and November 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Using time-lapse imaging (TLI), the precise time of pronuclei appearance and disappearance was recorded, where applicable, and the number of oocytes with two pronuclei observable during 10 30-min intervals from 15 hpi to 20 hpi was determined. MAIN RESULTS AND THE ROLE OF CHANCE: Between 15 and 17.5 hpi, the average number of oocytes exhibiting normal fertilisation, elicited as two pronuclei, was 98.19% with the highest proportion of oocytes having visible pronuclei at 16-16.5 hpi (98.32%). At 18-18.5 hpi, the number of visible pronuclei reduced to 95.53% and continued to fall to 87.02% at 19.5-20 hpi. LIMITATIONS, REASONS FOR CAUTION: The authors' expectation is that these findings are transferable to other settings, however it is possible that, with alternative culture media and incubation environments, calibration of this timing may be required. As data cannot readily be recorded for pronuclear appearance for IVF-derived embryos, it is not possible to determine the optimum time to perform the fertilisation assessment for IVF-derived embryos. WIDER IMPLICATIONS OF THE FINDINGS: By fine-tuning the time at which fertilisation assessment takes place the accuracy of the assessment can be increased to maximise the number of fertilised oocytes identified, thereby increasing the number of usable embryos for the patient. Without TLI and following current consensus guidelines, over 11% (n = 3000) of oocytes would have been marked as unfertilised within this cohort. Further to this, depending on the time of a standard fertilisation assessment, up to 300 embryos which resulted in live births could have been categorised as unfertilised, as they presented no visible pronuclei at the conventional assessment time-point. STUDY FUNDING/COMPETING INTEREST(S): A.C. is a minor shareholder in CARE Fertility Limited. Validated algorithmic time-lapse embryo selection is offered to patients at CARE Fertility at an additional charge as an adjuvant treatment option. TRIAL REGISTRATION NUMBER: N/A.

A European curriculum for nurses working in haemophilia.

INTRODUCTION: Currently, there is no consensus on education required to develop haemophilia nursing. The aim was to develop a curriculum for haemophilia nurses that could be used as a resource in Europe. This could form a basis for continuous professional development and used in the preparation of specialized educational programmes. METHODS: The EAHAD nurses working group set out to describe the skills and knowledge needed for a nurse to work in this specialty. This was considered at two levels: basic requirements and at a more advanced level. The working group acted as a focus group for this project drawing on existing specialist training, national role definitions, competencies and results of the EAHAD Nurses survey (2012). A template was populated with the knowledge base and the skills required. RESULTS: Themes were analysed and information generated organized into domains: content of curriculum; learning outcomes, defined in terms of knowledge, skills, behaviour and attitudes; and suggestions for teaching methods. For curriculum content the following domains were identified: Applied biological science; treatment and management of haemophilia and associated disorders; genetic practice; care management of affected carriers and women; the impact of living with bleeding disorders; evidence base and applied research in haemophilia practice; and, the specialist role of the haemophilia nurse. Examples are given for teaching and learning process. CONCLUSION: This curriculum is intended for use as a strategic resource to outline education for the haemophilia nurse and contribute to the standardization and benchmarking of haemophilia nursing care and thus to improvement in the quality of patient care.

A multivariate statistical approach and water quality index for water quality assessment for the Rokel river in Sierra Leone.

The main aim of the study was to use multivariate statistical approach to determine the relationship between parameters, identify the factors affecting the quality of water and interpret and group the water quality parameters. Water quality data was collected during two seasons; wet season spanning from June to August 2019 and dry season spanning from February to April 2019. The physiochemical and microbial parameters measured from the sampling process were turbidity, temperature, pH, electric conductivity, total hardness, calcium carbonates, total dissolved solid (TDS), dissolved oxygen (DO), total suspended solids (TSS), iron, nitrate, phosphate, potassium, sulphate, chromium, fluoride, e. coli and coliform. A total of 406 data set were collected and analysed using Principal Component Analysis, water quality index, cluster analysis and analysis of variance (ANOVA). These data sets were tested for sampling adequacy using Kaiser-Meyer-Olkin and Bartlett's Test and the result on the Kaiser-Meyer-Olkin Measure of Sampling Adequacy obtained was 0.615. The analysis yields Five PCs extraction with eigenvalues >1. These components explained 82.628% of the total variance of the entire components. The maximum water quality index 13 which indicated a grade A and can be treated for water supply. The following parameters Chromium 0.39 mg/l, Iron 1.88 mg/l, turbidity 18.66NTU, Phosphates 26.00 mg/l and fluorides 1.75 mg/l exceeded the WHO guidelines for drinking water. The mean values electrical conductivity is 12.26 µS/cm, 31.8 µS/cm for rain and dry seasons respectively., The following parameters Turbidity, Total Dissolved Solid, Total Suspended solids, Iron, Phosphate, Fluoride and Sulphate shows variation with High during the rain and low during the dry season with significant statical difference with a p value < 0.05. Whereas there is difference between the seasonal values of chromium, Nitrate and Potassium. The ANOVA resulted in P-value >0.05 which indicated no statistically significant different for chromium, Nitrate and Potassium. The seasonal variation was corroborated by cluster analysis with two clusters of C1 and C2. The PCs analysis, cluster analysis and ANOVA gave detailed characterization of the source and group correlation amongst the physiochemical and microbial parameters.

Direct observations of energy transfer from resonant electrons to whistler-mode waves in magnetosheath of Earth.

Electromagnetic whistler-mode waves in space plasmas play critical roles in collisionless energy transfer between the electrons and the electromagnetic field. Although resonant interactions have been considered as the likely generation process of the waves, observational identification has been extremely difficult due to the short time scale of resonant electron dynamics. Here we show strong nongyrotropy, which rotate with the wave, of cyclotron resonant electrons as direct evidence for the locally ongoing secular energy transfer from the resonant electrons to the whistler-mode waves using ultra-high temporal resolution data obtained by NASA's Magnetospheric Multiscale (MMS) mission in the magnetosheath. The nongyrotropic electrons carry a resonant current, which is the energy source of the wave as predicted by the nonlinear wave growth theory. This result proves the nonlinear wave growth theory, and furthermore demonstrates that the degree of nongyrotropy, which cannot be predicted even by that nonlinear theory, can be studied by observations.

Evidence for early specialized processing of speech formant information in anterior and posterior human auditory cortex.

Many speech sounds, such as vowels, exhibit a characteristic pattern of spectral peaks, referred to as formants, the frequency positions of which depend both on the phonological identity of the sound (e.g. vowel type) and on the vocal-tract length of the speaker. This study investigates the processing of formant information relating to vowel type and vocal-tract length in human auditory cortex by measuring electroencephalographic (EEG) responses to synthetic unvoiced vowels and spectrally matched noises. The results revealed specific sensitivity to vowel formant information in both anterior (planum polare) and posterior (planum temporale) regions of auditory cortex. The vowel-specific responses in these two areas appeared to have different temporal dynamics; the anterior source produced a sustained response for as long as the incoming sound was a vowel, whereas the posterior source responded transiently when the sound changed from a noise to a vowel, or when there was a change in vowel type. Moreover, the posterior source appeared to be largely invariant to changes in vocal-tract length. The current findings indicate that the initial extraction of vowel type from formant information is complete by the level of non-primary auditory cortex, suggesting that speech-specific processing may involve primary auditory cortex, or even subcortical structures. This challenges the view that specific sensitivity to speech emerges only beyond unimodal auditory cortex.

Neural Network Repair of Lossy Compression Artifacts in the September 2015 to March 2016 Duration of the MMS/FPI Data Set.

During the September 2015 to March 2016 duration (sometimes referred to as Phase 1A) of the Magnetospheric Multiscale Mission, the Dual Electron Spectrometers (DES) were configured to generously utilize lossy compression. While this maximized the number of velocity distribution functions downlinked, it came at the expense of lost information content for a fraction of the frames. Following this period of lossy compression, the DES was reconfigured in a way that allowed for 95% of the frames to arrive to the ground without loss. Using this high-quality set of frames from on-orbit observations, we compressed and decompressed the frames on the ground to create a side-by-side record of the compression effect. This record was used to drive an optimization method that (a) derived basis functions capable of approximating the lossless sample space and with nonnegative coefficients and (b) fitted a function which maps the lossy frames to basis weights that recreate the frame without compression artifacts. This method is introduced and evaluated in this paper. Data users should expect a higher level of confidence in the absolute scale of density/temperature measurements and notice less sinusoidal bias in the velocity X and Y components (GSE).

Interaural correlation and the binaural summation of loudness.

The effect of interaural correlation (rho) on the loudness for noisebands was measured using a loudness-matching task in naive listeners. The task involved a sequence of loudness comparisons for which the intensity of one stimulus in a given comparison was varied using a one-up-one-down adaptive rule. The task provided an estimate of the level difference (in decibels) for which two stimulus conditions have equal loudness, giving measures of loudness difference in equivalent decibel units (dB(equiv)). Concurrent adaptive tracks measured loudness differences between rho=1, 0, and -1 and between these binaural stimuli and the monaural case for various noisebands. For all noisebands, monaural stimuli required approximately 6 dB higher levels than rho=1 for equal loudness. For most noisebands, rho=1 and rho=-1 were almost equal in loudness, with rho=-1 being slightly louder in the majority of measurements, while rho=0 was about 2 dB(equiv) louder than rho=1 or rho=-1. However, noisebands with significant high-frequency energy showed smaller differences: for 3745-4245 Hz, rho=0 was only about 0.85 dB(equiv) louder than rho=+/-1, and for 100-5000 Hz it was non-significantly louder (perhaps 0.7 dB(equiv)).

Living with amyotrophic lateral sclerosis/motor neurone disease (ALS/MND): decision-making about 'ongoing change and adaptation'.

AIMS AND OBJECTIVES: To present a model that explicates the dimensions of change and adaptation as revealed by people who are diagnosed and live with amyotrophic lateral sclerosis/motor neurone disease. BACKGROUND: Most research about amyotrophic lateral sclerosis/motor neurone disease is medically focused on cause and cure for the illness. Although psychological studies have sought to understand the illness experience through questionnaires, little is known about the experience of living with amyotrophic lateral sclerosis/motor neurone disease as described by people with the disease. DESIGN: A grounded theory method of simultaneous data collection and constant comparative analysis was chosen for the conduct of this study. METHODS: Data collection involved in-depth interviews, electronic correspondence, field notes, as well as stories, prose, songs and photographs important to participants. QSR NVivo 2 software was used to manage the data and modelling used to illustrate concepts. FINDINGS: Participants used a cyclic, decision-making pattern about 'ongoing change and adaptation' as they lived with the disease. This pattern formed the basis of the model that is presented in this paper. CONCLUSION: The lives of people living with amyotrophic lateral sclerosis/motor neurone disease revolve around the need to make decisions about how to live with the disease progression and their deteriorating abilities. Life decisions were negotiated by participants to maintain a sense of self and well-being in the face of change. RELEVANCE TO CLINICAL PRACTICE: The 'ongoing change and adaptation' model is a framework that can guide practitioners to understand the decision-making processes of people living with amyotrophic lateral sclerosis/motor neurone disease. Such understanding will enhance caring and promote models of care that are person-centred. The model may also have relevance for people with other life limiting diseases and their care.

A description of the 'smile sign' and multi-pass technique for endovenous laser ablation of large diameter great saphenous veins.

Aims To report on great saphenous vein diameter distribution of patients undergoing endovenous laser ablation for lower limb varicose veins and the ablation technique for large diameter veins. Methods We collected retrospective data of 1929 (943 left leg and 986 right leg) clinically incompetent great saphenous vein diameters treated with endovenous laser ablation over five years and six months. The technical success of procedure, complications and occlusion rate at short-term follow-up are reported. Upon compression, larger diameter veins may constrict asymmetrically rather than concentrically around the laser fibre (the 'smile sign'), requiring multiple passes of the laser into each dilated segment to achieve complete ablation. Results Of 1929 great saphenous veins, 334 (17.31%) had a diameter equal to or over 15 mm, which has been recommended as the upper limit for endovenous laser ablation by some clinicians. All were successfully treated and occluded upon short-term follow-up. Conclusion We suggest that incompetent great saphenous veins that need treatment can always be treated with endovenous laser ablation, and open surgery should never be recommended on vein diameter alone.

Anatomical abnormalities of the pelvic venous system and their implications for endovascular management of pelvic venous reflux.

Background Pelvic venous reflux is often treated with pelvic vein embolisation; however, atypical pelvic venous anatomy may provide therapeutic challenges. Methods We retrospectively reviewed seven patient files and reported symptoms, diagnostic imaging, aberrant anatomy and means by which the interventional radiologist successfully completed the procedure. Any follow-up data were included if available. Results Four anatomical abnormalities were found: internal iliac veins draining into the contralateral common iliac vein, duplicated inferior vena cava, reverse-angle renal veins with atypical left ovarian vein drainage and direct drainage of the internal iliac vein to the inferior vena cava. All patients were successfully treated with pelvic vein embolisation. Conclusion Abnormal embryologic development may cause variable pelvic venous anatomy. Knowledge of this will enable interventional radiologists to successfully treat such patients.

A micro-scale plasma spectrometer for space and plasma edge applications (invited).

A plasma spectrometer design based on advances in lithography and microchip stacking technologies is described. A series of curved plate energy analyzers, with an integrated collimator, is etched into a silicon wafer. Tests of spectrometer elements, the energy analyzer and collimator, were performed with a 5 keV electron beam. The measured collimator transmission and energy selectivity were in good agreement with design targets. A single wafer element could be used as a plasma processing or fusion first wall diagnostic.

Phorbol ester translocation of protein kinase C in guinea-pig synaptosomes and the potentiation of calcium-dependent glutamate release.

The distribution of protein kinase C activity and specific phorbol ester binding sites between soluble and particulate fractions of isolated guinea-pig cerebral cortical synaptosomes is examined following preincubation with phorbol esters. Half-maximal decrease in cytosolic activity requires 10 nM 4 beta-phorbol myristoyl acetate. Specific [3H]phorbol dibutyrate binding sites are translocated from cytoplasmic to particulate fractions in parallel with protein kinase C activity. Depolarization of the plasma membrane by 30 mM KCl does not cause translocation of protein kinase C. 1 microM 4 beta-phorbol myristoyl acetate and 1 microM 4 beta-phorbol didecanoate (but not 1 microM 4 alpha-phorbol didecanoate) enhance the release of glutamate from synaptosomes partially depolarized by 10 mM KCl; however, 4 beta-phorbol myristoyl acetate is ineffective at 20 nM. 1 microM 4 beta-phorbol myristoyl acetate slightly increases the cytosolic free Ca2+ concentration of polarized synaptosomes, but not that following partial depolarization. 4 beta-Phorbol myristoyl acetate causes a concentration-dependent increase in the Ca2+-dependent glutamate release induced by sub-optimal ionomycin concentrations, but is without effect on the release induced by maximal ionomycin. It is concluded that phorbol esters stereospecifically enhance the Ca2+-sensitivity of glutamate release, but that higher concentrations may be required than for protein kinase C translocation in the same preparation. Instead the enhancement may be related to the rapid inactivation of protein kinase C which occurs with phorbol esters.

Strip-tract revascularization as a source of recurrent venous reflux following high saphenous tie and stripping: results at 5-8 years after surgery.

OBJECTIVE: We have previously reported strip-tract revascularization 1 year following high saphenous ligation and inversion stripping. This study reports the 5-8 year results in the same cohort. METHODS: Between 2000 and 2003, 72 patients presented with primary varicose veins and had undergone high saphenous ligation and inversion stripping plus phlebectomies with or without subfascial endoscopic perforator surgery. Of the 64 patients who had attended for follow-up at 1 year, 35 patients (male:female, 16:19; 39 legs) underwent duplex ultrasonography 5-8 years after surgery (response rate 55%). Duplex ultrasonography was performed and all strip-tract revascularization and reflux and groin neovascularization was documented. RESULTS: Eighty-two percent of legs of patients showed some evidence of strip-tract revascularization and reflux. Full and partial strip-tract revascularization and reflux was seen in 12.8% and 59% of limbs of patients, respectively, and 10.2% limbs of patients had neovascularization only at the saphenofemoral junction only. Seven limbs of patients showed no revascularization. CONCLUSION: Five to eight years after high saphenous tie and stripping, 82% of legs of patients showed some strip-tract revascularization and reflux and 12% showed total revascularization and reflux of the stripped great saphenous vein.

Fissure sealant retention: a comparison of three sealant types under field conditions.

Two two-year double-blind clinical trials were undertaken involving the newly-erupted first permanent molars of 133 children aged 5-6 years at the outset. In one study of 76 subjects, half the teeth were sealed with the filled sealants Prismashield or Estiseal. In the other study of 58 children, half were again sealed with Prismashield, and the others with the unfilled Concise white sealant, by a community dental service hygienist, as part of her routine dental duties. Subjects were examined under blind conditions at 6 monthly intervals and, by 24 months in the first study, 71 per cent of Prismashield sites were intact and caries-free, compared with only 53 per cent of Estiseal-treated tooth units (P less than 0.001). In the second study comparing Prismashield and Concise, by two years, 81 per cent of Prismashield resins were complete, compared with 88 per cent of the nonfilled Concise material. There were, however, no differences noted with respect to buccal and palatal site retention for either study. It can be concluded that Estiseal is a poorer material than Prismashield, certainly in relation to its bulk retention properties. Nonetheless it is possible that, along with other tooth-coloured/transparent resins, small fragments may not be as readily detectable as is the case with the unfilled Concise white sealant. However, as the abrasion resistance of unfilled materials is poorer than that of filled resins, the similar buccal/palatal site retention for Prismashield and Concise was also unexpected. Nevertheless this study illustrates again the value of sealant placement in the erupting first permanent molars of 5-6-year-old children, at a time when these teeth are most susceptible to carious attack.

Questioning behaviour in general practice: a pragmatic study.

OBJECTIVE: To study the extent to which general practitioners' questioning behaviour in routine practice is likely to encourage the adoption of evidence based medicine. DESIGN: Self recording of questions by doctors during consultations immediately followed by semistructured interview. SETTING: Urban Australian general practice. SUBJECTS: Random sample of 27 general practitioners followed over a half day of consultations. MAIN OUTCOME MEASURES: Rate of recording of clinical questions about patients' care which doctors would like answered; frequency with which doctors found answers to their questions. RESULTS: Doctors asked a total of 85 clinical questions, at a rate of 2.4 for every 10 patients seen. They found satisfactory answers to 67 (79%) of these questions. Doctors who worked in small practices (of one or two doctors) had a significantly lower rate of questioning than did those in larger practices (1.6 questions per 10 patients v 3.0 patients, P = 0.049). No other factors were significantly related to rate of questioning. CONCLUSIONS: These results do not support the view that doctors routinely generate a large number of unanswered clinical questions. It may be necessary to promote questioning behaviour in routine practice if evidence based medicine and other forms of self directed learning are to be successfully introduced.

Are interaural time and level differences represented by independent or integrated codes in the human auditory cortex?

Sound localization is important for orienting and focusing attention and for segregating sounds from different sources in the environment. In humans, horizontal sound localization mainly relies on interaural differences in sound arrival time and sound level. Despite their perceptual importance, the neural processing of interaural time and level differences (ITDs and ILDs) remains poorly understood. Animal studies suggest that, in the brainstem, ITDs and ILDs are processed independently by different specialized circuits. The aim of the current study was to investigate whether, at higher processing levels, they remain independent or are integrated into a common code of sound laterality. For that, we measured late auditory cortical potentials in response to changes in sound lateralization elicited by perceptually matched changes in ITD and/or ILD. The responses to the ITD and ILD changes exhibited significant morphological differences. At the same time, however, they originated from overlapping areas of the cortex and showed clear evidence for functional coupling. These results suggest that the auditory cortex contains an integrated code of sound laterality, but also retains independent information about ITD and ILD cues. This cue-related information might be used to assess how consistent the cues are, and thus, how likely they would have arisen from the same source.

Sensitivity to temporal fine structure and hearing-aid outcomes in older adults.

OBJECTIVE: To investigate the effect of sensitivity to temporal fine structure (TFS) on subjective measures of hearing aid outcome. DESIGN: Prior to receiving hearing aids, participants completed a test to assess sensitivity to TFS and two self-assessment questionnaires; the Glasgow Hearing Aid Benefit Profile (GHABP), and the Speech, Spatial and Qualities of hearing (SSQ-A). Follow-up appointments, comprised three self-assessment questionnaires; the GHABP, the SSQ-B, and the International Outcome Inventory for Hearing Aid Outcomes (IOI-HA). STUDY SAMPLE: 75 adults were recruited from direct referral clinics. RESULTS: Two thirds of participants were found to have good sensitivity to TFS; listeners with good sensitivity to TFS rated their hearing abilities higher at pre-fitting (SSQ-A) than those with poor sensitivity to TFS. At follow-up, participants with good sensitivity to TFS showed a smaller improvement on SSQ-B over listeners with poor sensitivity to TFS. Among the questionnaires, only the SSQ showed greater sensitivity to measure subjective differences between listeners with good and poor sensitivity to TFS. CONCLUSIONS: The clinical identification of a patient's ability to process TFS information at an early stage in the treatment pathway could prove useful in managing expectations about hearing aid outcomes.

Human decision making based on variations in internal noise: an EEG study.

Perceptual decision making is prone to errors, especially near threshold. Physiological, behavioural and modeling studies suggest this is due to the intrinsic or 'internal' noise in neural systems, which derives from a mixture of bottom-up and top-down sources. We show here that internal noise can form the basis of perceptual decision making when the external signal lacks the required information for the decision. We recorded electroencephalographic (EEG) activity in listeners attempting to discriminate between identical tones. Since the acoustic signal was constant, bottom-up and top-down influences were under experimental control. We found that early cortical responses to the identical stimuli varied in global field power and topography according to the perceptual decision made, and activity preceding stimulus presentation could predict both later activity and behavioural decision. Our results suggest that activity variations induced by internal noise of both sensory and cognitive origin are sufficient to drive discrimination judgments.

A systematic review of studies measuring and reporting hearing aid usage in older adults since 1999: a descriptive summary of measurement tools.

OBJECTIVE: A systematic review was conducted to identify and quality assess how studies published since 1999 have measured and reported the usage of hearing aids in older adults. The relationship between usage and other dimensions of hearing aid outcome, age and hearing loss are summarised. DATA SOURCES: Articles were identified through systematic searches in PubMed/MEDLINE, The University of Nottingham Online Catalogue, Web of Science and through reference checking. STUDY ELIGIBILITY CRITERIA: (1) participants aged fifty years or over with sensori-neural hearing loss, (2) provision of an air conduction hearing aid, (3) inclusion of hearing aid usage measure(s) and (4) published between 1999 and 2011. RESULTS: Of the initial 1933 papers obtained from the searches, a total of 64 were found eligible for review and were quality assessed on six dimensions: study design, choice of outcome instruments, level of reporting (usage, age, and audiometry) and cross validation of usage measures. Five papers were rated as being of high quality (scoring 10-12), 35 papers were rated as being of moderate quality (scoring 7-9), 22 as low quality (scoring 4-6) and two as very low quality (scoring 0-2). Fifteen different methods were identified for assessing the usage of hearing aids. CONCLUSIONS: Generally, the usage data reviewed was not well specified. There was a lack of consistency and robustness in the way that usage of hearing aids was assessed and categorised. There is a need for more standardised level of reporting of hearing aid usage data to further understand the relationship between usage and hearing aid outcomes.