Search for a Dark-Matter-Induced Cosmic Axion Background with ADMX.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

Experiences of Female Partners of People Transitioning Gender: A Feminist Interpretive Metasynthesis.

The needs of romantic partners of people transitioning gender remain neglected within academia and gender services. Following a systematic search, nine studies relating to female partners' experiences were subjected to a thematic metasynthesis. Four themes were generated and entitled Changes in sexual relationship; New roles and responsibilities; Identity and belonging; and Transformation and loss Results are considered in relation to the dominance of the gender-affirmation discourse. Limitations of the review and reviewed studies are highlighted. Clinical implications for couples and partners of people transitioning gender are offered.

Search for Invisible Axion Dark Matter in the 3.3-4.2 µeV Mass Range.

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 µeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.

Systems Biology Model of Cerebral Oxygen Delivery and Metabolism During Therapeutic Hypothermia: Application to the Piglet Model.

Hypoxic ischaemic encephalopathy (HIE) is a significant cause of death and disability. Therapeutic hypothermia (TH) is the only available standard of treatment, but 45-55% of cases still result in death or neurodevelopmental disability following TH. This work has focussed on developing a new brain tissue physiology and biochemistry systems biology model that includes temperature effects, as well as a Bayesian framework for analysis of model parameter estimation. Through this, we can simulate the effects of temperature on brain tissue oxygen delivery and metabolism, as well as analyse clinical and experimental data to identify mechanisms to explain differing behaviour and outcome. Presented here is an application of the model to data from two piglets treated with TH following hypoxic-ischaemic injury showing different responses and outcome following treatment. We identify the main mechanism for this difference as the Q10 temperature coefficient for metabolic reactions, with the severely injured piglet having a median posterior value of 0.133 as opposed to the mild injury value of 5.48. This work demonstrates the use of systems biology models to investigate underlying mechanisms behind the varying response to hypothermic treatment.

Impact of low-dose aspirin on adverse perinatal outcome: meta-analysis and meta-regression.

OBJECTIVE: To perform a meta-analysis and meta-regression of randomized controlled trials (RCTs) to evaluate the impact of low-dose aspirin (LDA) on perinatal outcome, independent of its effect on pre-eclampsia (PE), preterm birth and low birth weight. METHODS: An electronic search of EMBASE, PubMed, CENTRAL, PROSPERO and Google Scholar databases was performed to identify RCTs assessing the impact of LDA in pregnancy, published in English prior to May 2019, which reported perinatal outcomes of interest (placental abruption, delivery mode, low 5-min Apgar score, neonatal acidosis, neonatal intensive care unit admission, periventricular hemorrhage and perinatal death). Risk ratios (RR) and 95% CI were calculated and pooled for analysis. Analysis was stratified according to gestational age at commencement of treatment (≤ 16 weeks vs > 16 weeks) and subgroup analysis was performed to assess the impact of aspirin dose (< 100 mg vs ≥ 100 mg). Meta-regression was used to assess the impact of LDA on perinatal outcome, independent of the reduction in PE, preterm birth and low birth weight. RESULTS: Forty studies involving 34 807 participants were included. When LDA was commenced ≤ 16 weeks' gestation, it was associated with a significant reduction in the risk of perinatal death (RR, 0.47; 95% CI, 0.25-0.88; P = 0.02; number needed to treat, 92); however, this risk reduction was only seen when a daily dose of ≥ 100 mg was administered. If commenced > 16 weeks' gestation, LDA was associated with a significant reduction in 5-min Apgar score < 7 (RR, 0.75; 95% CI, 0.58-0.96; P = 0.02) and periventricular hemorrhage (RR, 0.68; 95% CI, 0.47-0.99; P = 0.04), but a trend towards an increase in the risk of placental abruption (RR, 1.20; 95% CI, 1.00-1.46; P = 0.06) was also noted. LDA was not associated with any significant increase in adverse events if commenced ≤ 16 weeks gestation. LDA had no effect on delivery mode, irrespective of the gestational age at which it was started. Meta-regression confirmed that the effect of LDA on perinatal death, when treatment was started ≤ 16 weeks' gestation, was independent of any reduction in the rate of PE and preterm birth. CONCLUSION: LDA improves some important perinatal outcomes, without increasing adverse events such as placental abruption or periventricular hemorrhage, and its utility, if commenced prior to 16 weeks' gestation, may be considered in a wider context beyond the prevention of PE or fetal growth restriction. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Impacto de la aspirina en dosis bajas en los resultados perinatales adversos: metaanálisis y metaregresión OBJETIVO: Realizar un metaanálisis y una metaregresión de ensayos controlados aleatorizados (ECA) para evaluar el impacto de la aspirina en dosis bajas (LDA, por sus siglas en inglés) en el resultado perinatal, independientemente de su efecto en la preeclampsia (PE), el parto pretérmino y el peso bajo al nacer. MÉTODOS: Se realizó una búsqueda electrónica en las bases de datos EMBASE, PubMed, CENTRAL, PROSPERO y Google Scholar para identificar ECA que hubieran evaluado el impacto de la LDA en el embarazo, publicados en inglés antes de mayo de 2019, que informaran sobre resultados perinatales de interés (desprendimiento de la placenta, modo de parto, baja puntuación de Apgar a los 5 minutos, acidosis neonatal, ingreso en la unidad de cuidados intensivos neonatales, hemorragia periventricular y muerte perinatal). Se calcularon los cocientes de riesgo (CR) y el IC del 95% y se combinaron para el análisis. El análisis se estratificó según la edad gestacional al comienzo del tratamiento (≤16 semanas vs. >16 semanas) y se realizaron análisis de subgrupos para evaluar el impacto de la dosis de aspirina (<100 mg vs ≥100 mg). Se utilizó la metarregresión para evaluar el impacto de LDA en el resultado perinatal, independientemente de la reducción de la PE, el parto pretérmino y el bajo peso al nacer. RESULTADOS: Se incluyeron 40 estudios con 34 807 participantes. Cuando se inició el tratamiento con LDA a ≤ 16 semanas de gestación, se asoció con una reducción significativa del riesgo de muerte perinatal (CR, 0,47; IC 95%, 0,25-0,88; P=0,02; número necesario a tratar, 92); sin embargo, esta reducción del riesgo sólo se observó cuando se administró una dosis diaria de ≥ 100 mg. Si se inició con una gestación de > 16 semanas, el tratamiento con LDA se asoció con una reducción significativa en la puntuación de Apgar a los 5 minutos < 7 (CR, 0,75; 95% CI, 0,58-0,96; P = 0,02) y la hemorragia periventricular (CR, 0,68; 95% CI, 0,47-0,99; P = 0,04), pero también se notó una tendencia al aumento en el riesgo de desprendimiento prematuro de la placenta (CR, 1,20; 95% CI, 1,00-1,46; P = 0.06). El tratamiento con LDA no se asoció con ningún aumento significativo de los eventos adversos si se inició a ≤ 16 semanas de gestación. El tratamiento con LDA no tuvo ningún efecto sobre el modo de parto, independientemente de la edad gestacional en la que se inició. La metaregresión confirmó que el efecto de la LDA en la muerte perinatal, cuando se inició el tratamiento a ≤ 16 semanas de gestación, fue independiente de cualquier reducción en la tasa de PE y de nacimientos prematuros. CONCLUSIÓN: El tratamiento con LDA mejora algunos resultados perinatales importantes, sin aumentar los eventos adversos como el desprendimiento de la placenta o la hemorragia periventricular, y su utilidad, si se inicia antes de las 16 semanas de gestación, puede considerarse en un contexto más amplio, más allá de la prevención de la PE o la restricción del crecimiento fetal. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

A pilot randomised controlled trial of the management of systolic blood pressure during endovascular thrombectomy for acute ischaemic stroke.

It is unknown whether systolic blood pressure augmentation during endovascular thrombectomy improves clinical outcomes. This pilot randomised controlled trial aimed to assess the feasibility of differential systolic blood pressure targeting during endovascular thrombectomy procedures for anterior circulation ischaemic stroke. Fifty-one eligible patients fulfilling the national criteria for endovascular thrombectomy were randomly assigned to receive either standard or augmented systolic blood pressure management from the start of anaesthesia to recanalisation of the target vessel. Systolic blood pressure targets for the standard and augmented groups were 130-150 mmHg and 160-180 mmHg, respectively. The study achieved all feasibility targets, including a recruitment rate of 3.5 participants per week and median (IQR [range]) of mean systolic blood pressure separation between groups of 139 (135-143 [115-154]) vs. 167 (150-175 [113-188]) mmHg, p < 0.001. Data completeness was 99%. Independent functional recovery at 90 days (modified Rankin Scale 0, 1 or 2) was achieved in 30 (59%) patients, which is consistent with previously published data. There were no safety concerns with trial procedures. In conclusion, a large randomised controlled efficacy trial of standard vs. augmented systolic blood pressure management during endovascular thrombectomy is feasible.

Perceived age and perceived health among a Chinese cohort: Does it mean the same thing?

BACKGROUND & AIMS: Previous investigations have aimed at investigating parameters affecting age perception on several ethnicities. Perceived health has been a newer focus on Caucasian skin, yet little is known on the skin features used to estimate the health status of Chinese women and we aimed to investigate whether these cues are the same as those used for age perception. METHODS: Age and health appearance of 276 Chinese female volunteers were estimated from their photographs by 1025 female naïve Chinese graders 20-69 years old. Models were built to predict perceived age and health from topographic, colour and biophysical measured variables, in two subsets of the studied volunteers: below and above 50 years. Machine learning-based predictive models for age and health perception were built on the collected data, and the interpretability of the models was established by measuring feature importance. RESULTS: Age perception was mostly driven by topographic features, particularly eye bags and eyelid sagging in the group below 50 years old. Wrinkles, notably from the lower part of the face and oval of the lower face, were found to be more relevant in the group above 50 years. Health appearance was primarily signalled by skin imperfections and global pigmentation in the subset below 50 years, whereas colour-related parameters and skin hydration acted as health cues for the subset above 50 years. CONCLUSION: Distinct skin features were acting as cues for age perception and/or health perception and varied per age subset. Their contribution should be borne in mind when designing products for 'younger looking skin' and 'healthier looking skin'.

OBJECTIF: Des études se sont penchées sur les paramètres cutanés influant sur la perception de l'âge, et ce sur plusieurs groups ethniques. La santé perçue quant à elle est un focus plus récent, avec des données publiées sur les peaux caucasiennes, au contraire des peaux chinoises. Nous avons donc décidé d'étudier quels sont ces paramètres cutanés influant sur la santé perçue et s'ils diffèrent de ceux utilisés dans la perception de l'âge, au sein d'un panel de femmes chinoises. MÉTHODES: L'âge et la santé cutanée de 276 femmes chinoises ont été estimés à partir de leurs photographies par un panel de 1025 évaluatrices naïves âgées de 20 à 69 ans. Des modèles ont été construits pour prédire l'âge et la santé perçus à partir de paramètres cutanés topographiques, de couleur et biophysiques, dans deux groupes d'âges différents : en dessous et au-dessus de 50 ans. Des modèles prédictifs basés sur l'apprentissage automatique (Machine learning) pour la perception de l'âge et de la santé ont été construits à partir des données collectées et l'interprétabilité des modèles a été établie en mesurant l'importance des paramètres cutanés. RÉSULTATS: Nos résultats montrent que la perception de l'âge repose principalement sur des paramètres topographiques, en particulier les poches sous les yeux et l'affaissement de la paupière, pour le groupe âgé de moins de 50 ans. Les rides, notamment celles de la partie basse du visage et le contour de la partie basse du visage se sont montrés pertinents pour estimer l'âge dans le groupe âgé de plus de 50 ans. La perception de la santé est principalement affectée par les imperfections cutanées et la pigmentation dans le groupe âgé de moins de 50 ans, tandis que des paramètres liés à la couleur et l'hydratation prennent le relais pour le groupe âgé de plus de 50 ans. CONCLUSION: Des paramètres cutanés de nature diverse sont pris en compte selon que l'on essaye d'estimer l'âge ou la santé, et ce en fonction du groupe d'âge étudié. Leur contribution doit être prise en compte lors de la conception de produits pour une «peau d'apparence plus jeune¼ et une «peau d'apparence plus saine¼.

Multiple sclerosis: long-term outcomes in ethnic minorities. Analysis of a UK population-based registry.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is most frequent in Caucasian populations. However, studies of MS in other ethnic groups may offer unique insights into genetic and environmental influences on the disease, and data on long-term outcomes in these patients is limited. In this work clinical features and time to disability milestones were investigated in ethnic minority (EM) patients with MS in a UK population and comparisons were made to a Caucasian cohort from the same region. METHODS: In all, 1949 MS patients (1866 Caucasian, 83 EM) were identified from a regional disease registry. Cox proportional hazards regression was used to analyse the time to Expanded Disability Status Scale (EDSS) 3.0, 4.0 and 6.0. RESULTS: Ethnic minority patients were younger at disease onset (28.6 years vs. 32.8 years, P = 0.001), and primary progressive MS was less common (EM 4.8%, Caucasian 11.6%, P = 0.03). After correction for clinical variables, ethnicity was associated with time to EDSS 3.0 [EM: hazard ratio (HR) 1.75, P < 0.0001] and 4.0 (HR 1.46, P = 0.03), but not 6.0 (HR 1.5, P = 0.05). CONCLUSIONS: Ethnic minority patients reach early levels of fixed disability more rapidly than Caucasian patients, but this effect diminishes at later stages of the disease. This has implications for clinical management of these patients.

Antera 3D capabilities for pore measurements.

BACKGROUND: The cause of enlarged pores remains obscure but still remains of concern for women. To complement subjective methods, bioengineered methods are needed for quantification of pores visibility following treatments. The study objective was to demonstrate the suitability of pore measurements from the Antera 3D. MATERIAL AND METHODS: Pore measurements were collected on 22 female volunteers aged 18-65 years with the Antera 3D, the DermaTOP and image analysis on photographs. Additionally, 4 raters graded pore size on photographs on a scale 0-5. Repeatability of Antera 3D parameters was ascertained and the benefit of a pore minimizer product on the cheek was assessed on a sub panel of seven female volunteers. RESULTS: Pore parameters using the Antera were shown to depict pore severity similar to raters on photographs, except for Max Depth. Mean pore volume, mean pore area and count were moderately correlated with DermaTOP parameters (up to r = .50). No relationship was seen between the Antera 3D and pore visibility analysis on photographs. The most repeatable parameters were found to be mean pore volume, mean pore area and max depth, especially for the small and medium filters. The benefits of a pore minimizer product were the most striking for mean pore volume and mean pore area when using the small filter for analysis, rather than the medium/large ones. CONCLUSION: Pore measurements with the Antera 3D represent a reliable tool for efficacy and field studies, with an emphasis of the small filter for analysis for the mean pore volume/mean pore area parameters.

Investigation of Confounding Factors in Measuring Tissue Saturation with NIRS Spatially Resolved Spectroscopy.

Performing absolute measurements of tissue saturation of the brain with near-infrared spectroscopy (NIRS) is a clinically desirable brain monitoring tool. Tissue oxygenation index (TOI) is an indicator of absolute tissue mixed arterial and venous oxygen saturation, and can be calculated using a NIRS technique called spatially resolved spectroscopy (SRS). SRS instruments measure the change of light attenuation with distance by using multiple light source-detector distances at two or more wavelengths. The aim of the study is to use broadband NIRS SRS data to investigate the effects on the calculation of TOI of different parameters: wavelength selection, scattering dependence, source-detector distance, and resolving for water. In total, 55 neonates with hypoxic-ischemic encephalopathy were monitored using a broadband multi-distance continuous wave NIRS system; 172 datasets were recorded. Using a "Standard" approach, TOI values between 0 and 100% ("good") were calculated in 157/172 datasets with a mean TOI of 50%. By changing the wavelength selection, the number of "good" data sets increases to 165/172 with a mean of 60%. Alteration of the dependence of scattering on wavelength acts as a constant which shifts the absolute value of TOI significantly (p < 0.05), demonstrating the importance of having a subject-appropriate estimation of scattering dependence. In general, changing the combination of source-detector distances does not significantly alter the TOI (the mean TOI ranges from 41% to 53%) which suggests that the algorithm is robust to different source-detector combinations. The study shows the broadband NIRS SRS algorithm gives the opportunity to explore the calculation of TOI and could further improve the measurement of tissue saturation in a clinical setting.

The prevalence of diabetes-specific emotional distress in people with Type 2 diabetes: a systematic review and meta-analysis.

AIMS: Psychological comorbidity, such as depression and/or diabetes-specific emotional distress (diabetes distress), is widespread in people with Type 2 diabetes and is associated with poorer treatment outcomes. Although extensive research into the prevalence of depression has been conducted, the same attention has not been given to diabetes distress. The aim of this systematic review was to determine the overall prevalence of diabetes distress in people with Type 2 diabetes. METHODS: Seven databases were searched to identify potentially relevant studies; eligible studies (adult population aged > 18 years with Type 2 diabetes and an outcome measure of diabetes distress) were selected and appraised independently by two reviewers. Multiple fixed- and random-effects meta-analyses were performed to synthesize the data; with primary analyses to determine the overall prevalence of diabetes distress in people with Type 2 diabetes, and secondary meta-analyses and meta-regression to explore the prevalence across different variables. RESULTS: Fifty-five studies (n = 36 998) were included in the meta-analysis and demonstrated an overall prevalence of 36% for diabetes distress in people with Type 2 diabetes. Prevalence of diabetes distress was significantly higher in samples with a higher prevalence of comorbid depressive symptoms and a female sample majority. CONCLUSIONS: Diabetes distress is a prominent issue in people with Type 2 diabetes that is associated with female gender and comorbid depressive symptoms. It is important to consider the relationship between diabetes distress and depression, and the significant overlap between conditions. Further work is needed to explore psychological comorbidity in Type 2 diabetes to better understand how best to identify and appropriately treat individuals.

Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort.

BACKGROUND: Alemtuzumab has recently been approved for treatment of relapsing MS, but concerns remain about its use since long-term studies of adverse events remain limited. Furthermore, a clear understanding of its application and durability of effect in clinical practice has yet to evolve. OBJECTIVES: To investigate long-term efficacy and safety outcomes in a multicentre cohort of patients treated with alemtuzumab. METHODS: Patients treated from 2000 and followed-up at three regional centres were identified. Baseline and prospective data were obtained and validated by clinical record review. RESULTS: One hundred patients were identified with a mean follow-up of 6.1 years (range 1-13). Forty patients were retreated with at least one further treatment cycle. Annualized relapse rates fell from 2.1 to 0.2 (p<0.0001) post-treatment and were sustained for up to eight years of follow-up. Mean change in EDSS score was +0.14. Forty-seven patients developed secondary autoimmunity. CONCLUSION: Observed reduction in relapse rates reflected those reported in clinical trials, but we were unable to corroborate previous observations of disability reversal. 40% of patients required additional treatment cycles. Autoimmune adverse events were common, occurring at a higher rate than previously reported, but were largely predictable, and could be managed effectively within a rigorous monitoring regime.

The impact of FDG-PET/CT in the management of patients with vulvar and vaginal cancer.

OBJECTIVES: To evaluate the changes in prognostic impression and patient management following PET/CT in patients with vulvar and vaginal carcinoma; and to compare PET/CT findings with those of conventional imaging modalities. METHODS: We summarized prospectively and retrospectively collected data for 50 consecutive patients from our institution that enrolled in the National Oncologic PET Registry and underwent FDG-PET/CT for a suspected or known primary or recurrent vulvar/vaginal cancer. RESULTS: 54/83 (65%) studies included had a diagnosis of vulvar cancer, and the remaining 29/83 (35%), a diagnosis of vaginal cancer. Following FDG-PET/CT, the physician's prognostic impression changed in 51% of cases. A change in patient management, defined as a change to/from a non-interventional strategy (observation or additional imaging), to/from an interventional strategy (biopsy or treatment), was documented in 36% of studies. The electronic records demonstrated that 95% of the management strategies recorded in the physician questionnaires were implemented as planned. MRI and/or CT were performed within one month of the FDG-PET/CT in 20/83 (24%) and 28/83 (34%) cases, respectively. FDG-PET/CT detected nodes suspicious for metastases on 29/83 (35%) studies performed. MRI and CT detected positive nodes on 6 and 11 studies respectively. Distant metastases were identified in 10 cases imaged with FDG-PET and 5 cases that had additional conventional CT imaging. All suspicious lesions seen on CT were positively identified on PET/CT. In 4 cases, an abnormality identified on PET/CT, was not seen on diagnostic CT. CONCLUSIONS: FDG-PET/CT may play an important role in the management of vulvar and vaginal carcinoma.

Site-specific clinical disease onset in multiple sclerosis.

BACKGROUND AND PURPOSE: Multiple sclerosis is a chronic inflammatory disorder of the central nervous system characterized by acute episodes of neurological dysfunction thought to reflect focal areas of demyelination occurring in clinically eloquent areas. These symptomatic relapses are generally considered to be random clinical events occurring without discernible pattern. The hypothesis that relapses may follow a predetermined sequence and may provide insights into underlying pathological processes was investigated. METHODS: Employing prospective clinical database data from 1482 patients who had experienced one or more consecutive relapses were analysed. Using regression analysis, site and symptom of index event were compared with those of first relapse. RESULTS: It is demonstrated that following disease ignition subsequent relapses may not be random events but dependent on characteristics of the index event. All anatomical sites were more likely to be affected in the first relapse if that site had been involved in the index event with a similar association observed when comparing by symptoms. CONCLUSION: These findings have importance in understanding the evolution of the disease and predicting individual disease progression and may aid with patient counselling and management.

Diagnostic accuracy and limitations of post-mortem MRI for neurological abnormalities in fetuses and children.

AIM: To compare the diagnostic accuracy of non-invasive cerebral post-mortem magnetic resonance imaging (PMMRI) specifically for cerebral and neurological abnormalities in a series of fetuses and children, compared to conventional autopsy. MATERIALS AND METHODS: Institutional ethics approval and parental consent was obtained. Pre-autopsy cerebral PMMRI was performed in a sequential prospective cohort (n = 400) of fetuses (n = 277; 185 ≤ 24 weeks and 92 > 24 weeks gestation) and children <16 years (n = 123) of age. PMMRI and conventional autopsy findings were reported blinded and independently of each other. RESULTS: Cerebral PMMRI had sensitivities and specificities (95% confidence interval) of 88.4% (75.5 to 94.9), and 95.2% (92.1 to 97.1), respectively, for cerebral malformations; 100% (83.9 to 100), and 99.1% (97.2 to 99.7) for major intracranial bleeds; and 87.5% (80.1 to 92.4) and 74.1% (68 to 79.4) for overall brain pathology. Formal neuropathological examination was non-diagnostic due to maceration/autolysis in 43/277 (16%) fetuses; of these, cerebral PMMRI imaging provided clinically important information in 23 (53%). The sensitivity of PMMRI for detecting significant ante-mortem ischaemic injury was only 68% (48.4 to 82.8) overall. CONCLUSIONS: PMMRI is an accurate investigational technique for identifying significant neuropathology in fetuses and children, and may provide important information even in cases where autolysis prevents formal neuropathological examination; however, PMMRI is less sensitive at detecting hypoxic-ischaemic brain injury, and may not detect rarer disorders not encountered in this study.

The psychological impact of predictive genetic testing for Huntington's disease: a systematic review of the literature.

Huntington's disease (HD) is a neurodegenerative genetic condition for which a predictive genetic test by mutation analysis has been available since 1993. However, whilst revealing the future presence of the disease, testing may have an adverse psychological impact given that the disease is progressive, incurable and ultimately fatal. This review seeks to systematically explore the psychological impact of genetic testing for individuals undergoing pre-symptomatic mutation analysis. Three databases (Medline, PsycInfo and Scopus) were interrogated for studies utilising standardised measures to assess psychological impact following predictive genetic testing for HD. From 100 papers initially identified, eight articles were eligible for inclusion. Psychological impact of predictive genetic testing was not found to be associated with test result. No detrimental effect of predictive genetic testing on non-carriers was found, although the process was not found to be psychologically neutral. Fluctuation in levels of distress was found over time for carriers and non-carriers alike. Methodological weaknesses of published literature were identified, notably the needs of individuals not requesting genetic testing, as well as inadequate support for individuals registering elevated distress and declining post-test follow-up. Further assessment of these vulnerable individuals is warranted to establish the extent and type of future psychological support.

Brain mitochondrial oxidative metabolism during and after cerebral hypoxia-ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near-infrared spectroscopy.

BACKGROUND: Multimodal measurements combining broadband near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy ((31)P MRS) assessed associations between changes in the oxidation state of cerebral mitochondrial cytochrome-c-oxidase (Δ[oxCCO]) and (31)P metabolite peak-area ratios during and after transient cerebral hypoxia-ischemia (HI) in the newborn piglet. METHODS: Twenty-four piglets (aged<24 h) underwent transient HI (inspired oxygen fraction 9% and bilateral carotid artery occlusion for ~20 min). Whole-brain (31)P MRS and NIRS data were acquired every minute. Inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp were measured by (31)P MRS and were plotted against Δ[oxCCO] during HI and recovery (epp=exchangeable phosphate pool=Pi+PCr+2γ-NTP+ß-NTP). RESULTS: During HI Δ[oxCCO], PCr/epp and NTP/epp declined and Pi/epp increased. Significant correlations were seen between (31)P ratios and Δ[oxCCO]; during HI a threshold point was identified where the relationship between Δ[oxCCO] and both NTP/epp and Pi/epp changed significantly. Outcome at 48 h related to recovery of Δ[oxCCO] and (31)P ratios 1h post-HI (survived: 1-h NTP/epp 0.22 ± 0.02, Δ[oxCCO] -0.29 ± 0.50 µM; died: 1-h NTP/epp 0.10 ± 0.04, Δ[oxCCO] -2.41 ± 1.48 µM). CONCLUSIONS: Both lowered Δ[oxCCO] and NTP/epp 1h post-HI indicated mitochondrial impairment. Animals dying before 48 h had slower recovery of both Δ[oxCCO] and (31)P ratios by 1 h after HI.

Pharmacokinetics of dexmedetomidine combined with therapeutic hypothermia in a piglet asphyxia model.

BACKGROUND: The highly selective α2 -adrenoreceptor agonist, dexmedetomidine, exerts neuroprotective, analgesic, anti-inflammatory and sympatholytic properties that may be beneficial for perinatal asphyxia. The optimal safe dose for pre-clinical newborn neuroprotection studies is unknown. METHODS: Following cerebral hypoxia-ischaemia, dexmedetomidine was administered to nine newborn piglets in a de-escalation dose study in combination with hypothermia (whole body cooling to 33.5°C). Dexmedetomidine was administered with a loading dose of 1 µg/kg and maintenance infusion at doses from 10 to 0.6 µg/kg/h. One additional piglet was not subjected to hypoxia-ischaemia. Blood for pharmacokinetic analysis was sampled pre-insult and frequently post-insult. A one-compartment linear disposition model was used to fit data. Population parameter estimates were obtained using non-linear mixed effects modelling. RESULTS: All dexmedetomidine infusion regimens led to plasma concentrations above those associated with sedation in neonates and children (0.4-0.8 µg/l). Seven out of the nine piglets with hypoxia-ischaemia experienced periods of bradycardia, hypotension, hypertension and cardiac arrest; all haemodynamic adverse events occurred in piglets with plasma concentrations greater than 1 µg/l. Dexmedetomidine clearance was 0.126 l/kg/h [coefficient of variation (CV) 46.6.%] and volume of distribution was 3.37 l/kg (CV 191%). Dexmedetomidine clearance was reduced by 32.7% at a temperature of 33.5°C. Dexmedetomidine clearance was reduced by 55.8% following hypoxia-ischaemia. CONCLUSIONS: Dexmedetomidine clearance was reduced almost tenfold compared with adult values in the newborn piglet following hypoxic-ischaemic brain injury and subsequent therapeutic hypothermia. Reduced clearance was related to cumulative effects of both hypothermia and exposure to hypoxia. High plasma levels of dexmedetomidine were associated with major cardiovascular complications.

Impact of anaesthetics and surgery on neurodevelopment: an update.

Accumulating preclinical and clinical evidence suggests the possibility of neurotoxicity from neonatal exposure to general anaesthetics. Here, we review the weight of the evidence from both human and animal studies and discuss the putative mechanisms of injury and options for protective strategies. Our review identified 55 rodent studies, seven primate studies, and nine clinical studies of interest. While the preclinical data consistently demonstrate robust apoptosis in the nervous system after anaesthetic exposure, only a few studies have performed cognitive follow-up. Nonetheless, the emerging evidence that the primate brain is vulnerable to anaesthetic-induced apoptosis is of concern. The impact of surgery on anaesthetic-induced brain injury has not been adequately addressed yet. The clinical data, comprising largely retrospective cohort database analyses, are inconclusive, in part due to confounding variables inherent in these observational epidemiological approaches. This places even greater emphasis on prospective approaches to this problem, such as the ongoing GAS trial and PANDA study.

A genome screen in multiple sclerosis reveals susceptibility loci on chromosome 6p21 and 17q22.

The population prevalence of multiple sclerosis is 0.1%; however, the risk of the disease in the siblings of affected individuals is very much higher at 3-5%. The importance of genetic factors in accounting for this increased risk is confirmed by the results of twin and adoption studies. Despite the evidence for a strong genetic effect, a weak major histocompatibility complex (MHC) association is the only consistently observed feature in the genetics of multiple sclerosis. Other candidates have been proposed, including genes encoding the immunoglobulin heavy chain, T cell receptor beta chain and APOC2, but none has yet been confirmed. Evidence for linkage and association to the myelin basic protein gene has been reported in a genetically isolated Finnish population, but it has not been possible to reproduce these results in other populations. We used a two-stage approach to search the human genome for the genes causing susceptibility to multiple sclerosis. Two principal regions of linkage are identified, chromosomes 17q22 and 6p21 (MHC). Our results are compatible with genetic models involving epistatic interaction between these and several additional genes.