Nanoscale LiZnN - Luminescent Half-Heusler Quantum Dots.

Colloidal semiconductor quantum dots are a well-established technology, with numerous materials available either commercially or through the vast body of literature. The prevalent materials are cadmium-based and are unlikely to find general acceptance in most applications. While the III-V family of materials is a likely substitute, issues remain about its long-term suitability, and other earth-abundant materials are being explored. In this report, we highlight a nanoscale half-Heusler semiconductor, LiZnN, composed of readily available elements as a potential alternative system to luminescent II-VI and III-V nanoparticle quantum dots.

Patient Characteristics and Variables Influencing Acute Medical Flow.

Waiting times are the most widely used indicator of patient flow. This project aims to analyse 24-hour variation in referrals and waiting times for patients referred to the Acute Medical Service (AMS). A retrospective cohort study was conducted at the AMS of Wales' largest hospital. Collected data included patient characteristics, referral times, waiting times and adherence to Clinical Quality Indicators (CQIs). Peak referral times were found between 11:00-19:00. Peak waiting times occurred between 17:00-01:00, which was longer on weekdays in comparison to weekends. Referrals between 17:00-21:00 had the longest waiting times with > 40% of patients failing both junior and senior CQIs. Mean and median age and NEWS were higher between 17:00-09:00. Weekday evening and nights are problematic for acute medical patient flow. Interventions, including workforce, should be targeted towards these findings.

Carbogen inhalation during non-convulsive status epilepticus: A quantitative exploratory analysis of EEG recordings.

OBJECTIVE: To quantify the effect of inhaled 5% carbon-dioxide/95% oxygen on EEG recordings from patients in non-convulsive status epilepticus (NCSE). METHODS: Five children of mixed aetiology in NCSE were given high flow of inhaled carbogen (5% carbon dioxide/95% oxygen) using a face mask for maximum 120s. EEG was recorded concurrently in all patients. The effects of inhaled carbogen on patient EEG recordings were investigated using band-power, functional connectivity and graph theory measures. Carbogen effect was quantified by measuring effect size (Cohen's d) between "before", "during" and "after" carbogen delivery states. RESULTS: Carbogen's apparent effect on EEG band-power and network metrics across all patients for "before-during" and "before-after" inhalation comparisons was inconsistent across the five patients. CONCLUSION: The changes in different measures suggest a potentially non-homogeneous effect of carbogen on the patients' EEG. Different aetiology and duration of the inhalation may underlie these non-homogeneous effects. Tuning the carbogen parameters (such as ratio between CO2 and O2, duration of inhalation) on a personalised basis may improve seizure suppression in future.

Referral rates of patients with diabetes to secondary care are inversely related to the prevalence of diabetes in each primary care practice and confidence in treatment, not to HbA1c level.

AIMS: To determine the factors affecting the referral rates of patients with diabetes from primary care to secondary care. METHODS: A study based on 66 GP surgeries in the Cardiff and Vale University Health Board (population: 515,581) was conducted. We included patients who had an established clinical diagnosis of diabetes (type 1 and type 2) from September 2017 to September 2018. HbA1c outcome data of GP surgeries were obtained from the Quality and Outcomes Framework (QOF) database published for 2018. Referral rates were obtained from the electronic referral database of Cardiff and Vale University Health Board over the same period, and this was adjusted according to the number of patients with diabetes in each GP surgery. Confidence level on the treatment of diabetes among GPs was assessed as a sub-study conducted in nine GP surgeries in the same area, using a self-administered questionnaire. Linear regression was undertaken to assess the relationship between adjusted referral rate and key factors which might influence prescribing rate. RESULTS: The average adjusted referral rate to secondary care in one year was 4.23% of patients with diabetes in each GP surgery, with a wide variation of 1.24% to 16.28%. The average percentage of patients with diabetes with HbA1c<59mmol/mol was 63.17% (range: 43.19-76.23%). The average confidence score of GPs in treating diabetes was 67% and ranged from 50-85% in the sub-study. Referral rates correlated inversely with the numbers of patients with diabetes in each practice ß=-0.32; (95% CI -0.57, -0.08) p=0.01, but there was no significant correlation with the HbA1c outcome ß=-0.13; (95% CI -0.39, 0.12); p=0.30. Borderline significant negative correlation was observed between referral rates and overall practice size ß=-0.23; (95% CI -0.48, 0.02) p=0.07. CONCLUSIONS: Referral rates of patients with diabetes to secondary care are determined by the number of patients with diabetes in each practice and confidence level in treatment, not by the overall practice size or HbA1c level. Ensuring quality training in diabetes care for primary care teams as well as the development of integrated diabetes care may be the best way to optimise the volume and appropriateness of referrals to secondary care.

TetraGrip - a four channel upper limb FES device for people with C5/C6 tetraplegia: device design and clinical outcome.

The TetraGrip is an inertial measurement unit-controlled surface upper limb FES device developed for improving hand functions of people with tetraplegia. The reliability of the control system and the repeatability and reproducibility of the device were assessed by analysing the results obtained when 14 able-bodied volunteers used the device. These volunteers were able to generate the control signals effectively once they had sufficient training. The two tetraplegic volunteers participated in a 12-week long clinical study (exercise, 4 weeks; functional tasks, 8 weeks), where they used the device to perform functional tasks. Outcome measures used were the grasp release test, the grip strength test, and the box and block test. Both tetraplegic volunteers showed improvement in performing the tasks specified in all outcome measures. The TetraGrip performed as intended when the able-bodied volunteers used it, and it improved the hand functions of both volunteers with tetraplegia. However, a larger clinical study is necessary to assess the performance of the device with a wider range of people with tetraplegia such as those with C5 complete/incomplete.

Thyroxine replacement: a clinical endocrinologist's viewpoint.

BACKGROUND: Hypothyroidism affects 2-5% of the general population. Patients with uncorrected disease suffer significant morbidity and have an increased risk of cardiovascular disease and neurocognitive impairment. Levothyroxine, the treatment of choice, is inexpensive, easy to administer and in most cases restores well-being while normalizing thyroid function. However, 30-50% of individuals on levothyroxine are either over-treated or under-treated and others remain dissatisfied with treatment despite achieving thyroid hormone concentrations within the laboratory reference interval. METHODS: This review is based on a systematic search of the literature for controlled trials, systematic reviews, guideline papers and cohort studies addressing best practice in thyroid hormone replacement. RESULTS: Recent decades have seen improvements in patient management strategies driven by a better appreciation of levothyroxine pharmacokinetics. However, aspects of therapy such as the optimal timing of medication, strategies to overcome treatment non-adherence and target thyroid stimulating hormone concentrations in pregnancy and in patients with differentiated thyroid cancer remain challenging. Furthermore, there is now a substantial body of literature on common genetic variations in the deiodinases and thyroid hormone transporters and their role in the local regulation of thyroid hormone delivery. The benefits of combination therapy with liothyronine and levothyroxine are uncertain, and while it is theoretically probable that subsets of genetically predisposed individuals will benefit from combination therapy the existing evidence is as yet limited. CONCLUSION: Despite the availability of thyroid hormone replacement for more than a century, there are still substantial challenges in practice and opportunities to improve treatment outcomes.

Iodine supplementation in pregnancy - is it time?

Iodine is essential for the synthesis of thyroid hormone and optimal foetal neurological development. Pregnant women living in borderline or moderate-severe iodine deficient areas are at particularly high risk of being iodine deficient, and this may have important clinical consequences, particularly for the neurocognitive development of the offspring. It is a substantial problem and many countries including the United Kingdom are mild-moderately iodine deficient. Although the detrimental effects of severe iodine deficiency are well recognized, the benefits of correcting mild-to-moderate iodine deficiency are unclear due to a lack of randomized controlled trials in this area. However, observational data increasingly indicate that there may be substantial health and economic benefits from correcting iodine deficiency in pregnancy. There is now a growing trend from learned societies that iodine supplementation should be utilized in pregnancy in countries with mild-to-moderate iodine deficiency. The dose of iodine supplement needs to reflect local iodine status and iodization policies and will need careful monitoring at the population level to ensure doses to prevent under/excess dosing which would undermine the potential benefits. National tailored guidance is therefore essential.

HYPOTHYROXINAEMIA AND BRAIN DEVELOPMENT.

The aim of this review is to indicate the current position on the role of thyroxine (T4) and fetal brain development with particular relevance to the human situation. Adequate maternal iodine nutrition and maternal circulating thyroxine (T4) concentrations are essential to ensure optimum T4 placental passage which in turn will ensure transport of T4 into fetal brain cells. These processes are discussed and the role of thyroid hormone transporters is considered. The emphasis on isolated maternal hypothyroxinaemia (IH) as an important factor affecting brain development is discussed from the animal experimental point of view as well as in the clinical setting. There is evidence of neurocognitive impairment as assessed by different modalities in children up to the age of 8 years and some suggestion of increased psychiatric disorder in older persons whose mothers had IH during gestation. Although international guidelines have not in general recommended thyroxine therapy for IH the recent demonstration of adverse obstetric outcomes in women with isolated maternal hypothyroxinaemia may warrant a revision of this strategy.

Upper limb functional electrical stimulation devices and their man-machine interfaces.

Functional Electrical Stimulation (FES) is a technique that uses electricity to activate the nerves of a muscle that is paralysed due to hemiplegia, multiple sclerosis, Parkinson's disease or spinal cord injury (SCI). FES has been widely used to restore upper limb functions in people with hemiplegia and C5-C7 tetraplegia and has improved their ability to perform their activities of daily living (ADL). At the time of writing, a detailed literature review of the existing upper limb FES devices and their man-machine interfaces (MMI) showed that only the NESS H200 was commercially available. However, the rigid arm splint doesn't fit everyone and prevents the use of a tenodesis grip. Hence, a robust and versatile upper limb FES device that can be used by a wider group of people is required.

Impact on activities of daily living using a functional electrical stimulation device to improve dropped foot in people with multiple sclerosis, measured by the Canadian Occupational Performance Measure.

BACKGROUND: Dropped foot is a common problem following multiple sclerosis. Functional electrical stimulation can elicit an active muscle contraction providing dorsiflexion and eversion. OBJECTIVE: To determine if the Odstock dropped foot stimulator (ODFS), improved activities of daily living for people with multiple sclerosis. METHOD: 64 people with unilateral dropped foot due to secondary progressive multiple sclerosis took part in a randomized controlled trial. Research volunteers were assigned to a group using the ODFS or a group who received physiotherapy exercises for 18 weeks. Outcome measures were the Canadian Occupational Performance Measure (COPM) and a falls diary. RESULTS: Results of 53 research volunteers are reported. Improvements in performance and satisfaction scores were greater in the ODFS group than the exercise group; (p < 0.05). Use of the ODFS was also perceived as effective in reducing tripping and increasing walking distance. The median number of falls were 5 in the ODFS group and 18 in the exercise group (p = 0.036) over the study period. CONCLUSION: The study shows that people with multiple sclerosis using the ODFS increased their COPM performance and satisfaction scores of their identified problems of activities of daily living more than a matched group who received physiotherapy exercises. ODFS users also experienced fewer falls.

A randomized trial to investigate the effects of functional electrical stimulation and therapeutic exercise on walking performance for people with multiple sclerosis.

BACKGROUND: Functional electrical stimulation (FES), is a means of producing a contraction in a paralyzed or weak muscle to enable function through electrical excitation of the innervating nerve. OBJECTIVE: This two-group randomized trial assessed the effects of single channel common peroneal nerve stimulation on objective aspects of gait relative to exercise therapy for people with secondary progressive multiple sclerosis (SPMS). METHODS: Forty-four people with a diagnosis of SPMS and unilateral dropped foot completed the trial. Twenty patients were randomly allocated to a group receiving FES and the remaining 24 to a group receiving a physiotherapy home exercise program for a period of 18 weeks. RESULTS: The exercise group showed a statistically significant increase in 10 m walking speed and distance walked in 3 min, relative to the FES group who showed no significant change in walking performance without stimulation. At each stage of the trial, the FES group performed to a significantly higher level with FES than without for the same outcome measures. CONCLUSION: Exercise may provide a greater training effect on walking speed and endurance than FES for people with SPMS. FES may provide an orthotic benefit when outcome is measured using the same parameters. More research is required to investigate the combined therapeutic effects of FES and exercise for this patient group.

The functional form of the lognormal distribution as a sum of decaying exponential and sinusoidal terms applied to the isometric pinch force of human fingers.

The transient data of the pinch force produced between the human forefinger and thumb have been shown to fit the functional form of the well-known lognormal density function. Isometeric force generation is achieved by the stochastic recruitment of individual motor units, which sum together. Evidence from animal and human experiments demonstrates that the force generation can be modelled by underdamped terms. It is shown that a lognormal time series (distribution) can be fitted to a sum of exponential decaying sinusoidal terms.

A microcontroller system for investigating the catch effect: functional electrical stimulation of the common peroneal nerve.

Correction of drop foot in hemiplegic gait is achieved by electrical stimulation of the common peroneal nerve with a series of pulses at a fixed frequency. However, during normal gait, the electromyographic signals from the tibialis anterior muscle indicate that muscle force is not constant but varies during the swing phase. The application of double pulses for the correction of drop foot may enhance the gait by generating greater torque at the ankle and thereby increase the efficiency of the stimulation with reduced fatigue. A flexible controller has been designed around the Odstock Drop Foot Stimulator to deliver different profiles of pulses implementing doublets and optimum series. A peripheral interface controller (PIC) microcontroller with some external circuits has been designed and tested to accommodate six profiles. Preliminary results of the measurements from a normal subject seated in a multi-moment chair (an isometric torque measurement device) indicate that profiles containing doublets and optimum spaced pulses look favourable for clinical use.

Electrical stimulation of abdominal muscles for control of blood pressure and augmentation of cough in a C3/4 level tetraplegic.

OBJECTIVES: Evaluation of a FES (Functional Electrical Stimulation) device for the relief of postural hypertension and augmentation of cough in a C3 ventilator-dependent tetraplegic. STUDY DESIGN: A single case study. SETTING: A supra regional spinal unit in the UK. METHOD: A dual channel stimulator was designed that allowed selection and initiation of two predetermined stimulation intensities using a chin controlled joystick. Two sets of 70 mm diameter electrodes were placed either side of the abdomen. Approximately 80 mA, 300 micros, 40 Hz was required for assisted cough while about 40 mA was required for maintenance of blood pressure. After eating, the lower level stimulus is self-administered every 3 to 5 min gradually increasing the time between groups of burst to once every hour after 90 min. RESULTS: Following eating, a blood pressure of 60/45 mmHg was recorded. After five 1 s bursts of stimulation in quick repetition, this was increased to 133/92 mmHg. After 2 min blood pressure had fallen to 124/86 mmHg and to 93/66 after a further 4 min. The electrical stimulation was then repeated, returning the blood pressure to the previous higher level. Measurement of peak expiratory flow showed an increase from 275 l/min for an unassisted cough to 425 l/min when using the device. CONCLUSION: The device is used every day. The user is now independent in coughing function and no longer requires suction or manual assistance. Maintenance of blood pressure has significantly improved his quality of life.

Restoration of tetraplegic hand function by use of the neurocontrol freehand system.

Nine tetraplegic patients with C5 or C6 level spinal cord lesions had the Freehand System, an eight channel Functional Electrical Stimulation device, implanted to allow of hand opening and grasp. This paper describes the surgical implementation of the system and the challenges encountered. Seven of the subjects are currently daily users of the device. One subject is unable to use the system due to disruption of bowel function when the system is used. A second subject suffered a lesion of the posterior interosseous nerve, but this was not thought to be related to system use. Additionally, one subject exhibited symptoms of autonomic dysreflexia, which were alleviated by reduction of the strength of the stimulus. Despite such problems, the Freehand system can significantly improve the functional ability of C5 and C6 lesion tetraplegics.

Indices to describe different muscle activation patterns, identified during treadmill walking, in people with spastic drop-foot.

This study was concerned with individuals who were unable to effectively dorsiflex their ankle when walking, as a result of a lesion of the central nervous system (CNS). Indices that categorise and quantify different patterns of calf and anterior tibial muscle activation patterns during treadmill walking have been derived from a sample of fifteen individuals with established hemiplegia following stroke and twelve age-matched individuals without impairment. As subjects walked on a treadmill, force sensitive foot-switches under the heel and first metatarsal head allowed EMG signals from the calf and anterior tibial muscles to be related to phases of the gait cycle. Normal activation periods for each muscle group were identified as percentiles of the gait cycle and indices for muscle activation periods were derived using ratios of integrated EMG during selected periods. Indices were derived that identified statistically significant differences, between normal and hemiplegic subjects, in calf activation during both push-off phase (P<0.001) and early stance phase (P<001), but not activation of tibialis anterior during swing (P=0.325) Observation suggested that integrated tibialis anterior activity during swing phase in hemiplegic subjects was not dissimilar to normal subjects, but the profile in hemiplegic subjects tended to lack the normal second peak of activity at initial foot contact. The reasons for drop-foot were shown to be varied and complex. The indices defined may be useful for directing therapy and measuring outcome.

Clinical use of the Odstock dropped foot stimulator: its effect on the speed and effort of walking.

OBJECTIVE: To assess the clinical effectiveness of the Odstock dropped foot stimulator by analysis of its effect on physiological cost index (PCI) and speed of walking. This functional electrical stimulation (FES) device stimulates the common peroneal nerve during the swing phase of gait. DESIGN: A retrospective study of patients who had used the device for 4 1/2 months. SUBJECTS: One hundred fifty-one patients with a dropped foot resulting from an upper motor neuron lesion. SETTING: A medical physics and biomedical engineering department of a district general hospital specializing in the clinical application of FES and a neurophysiotherapy department at a separate hospital. MAIN OUTCOME MEASURES: Changes in walking speed and effort of walking, as measured by PCI over a 10-meter course. RESULTS: There was a 92.7% compliance with treatment. Stroke patients showed a mean increase in walking speed of 27% (p<.01) and reduction in PCI of 31% (p<.01) with stimulation, and changes of 14% (p<.01) and 19% (p<.01), respectively, while not using the stimulator. Multiple sclerosis patients gained similar orthotic benefit but no "carry-over." CONCLUSIONS: The measured differences in walking with and without stimulation were statistically significant in the stroke and multiple sclerosis groups. In this study use of the stimulator improved walking. Those with stroke demonstrated a short-term "carry-over" effect.

Patients' perceptions of the Odstock Dropped Foot Stimulator (ODFS).

OBJECTIVE: To determine the perceived benefit, pattern and problems of use of the Odstock Dropped Foot Stimulator (ODFS) and the users' opinion of the service provided. DESIGN: Questionnaire sent in a single mailshot to current and past users of the ODFS. Returns were sent anonymously. SETTING: Outpatient-based clinical service. SUBJECTS: One hundred and sixty-eight current and 123 past users with diagnoses of stroke (CVA), multiple sclerosis (MS), incomplete spinal cord injury (SCI), traumatic brain injury (TBI) and cerebral palsy (CP). INTERVENTION: Functional electrical stimulation (FES) to correct dropped foot in subjects with an upper motor neuron lesion, using the ODFS. MAIN OUTCOME MEASURES: Purpose-designed questionnaire. RESULTS: Return rate 64% current users (mean duration of use 19.5 months) and 43% past users (mean duration of use 10.7 months). Principal reason cited for using equipment was a reduction in the effort of walking. Principal reasons identified for discontinuing were an improvement in mobility, electrode positioning difficulties and deteriorating mobility. There were some problems with reliability of equipment. Level of service provided was thought to be good. CONCLUSION: The ODFS was perceived by the users to be of considerable benefit. A comprehensive clinical follow-up service is essential to achieve the maximum continuing benefit from FES-based orthoses.