Viewpoint: filovirus haemorrhagic fever outbreaks: much ado about nothing?

The recent outbreak of Marburg haemorrhagic fever in the Democratic Republic of Congo has put the filovirus threat back on the international health agenda. This paper gives an overview of Marburg and Ebola outbreaks so far observed and puts them in a public health perspective. Damage on the local level has been devastating at times, but was marginal on the international level despite the considerable media attention these outbreaks received. The potential hazard of outbreaks, however, after export of filovirus from its natural environment into metropolitan areas, is argued to be considerable. Some avenues for future research and intervention are explored. Beyond the obvious need to find the reservoir and study the natural history, public health strategies for a more timely and efficient response are urgently needed

Two-dimensional superconductivity at the (111)LaAlO3_3/SrTiO3_3 interface

We report on the discovery and transport study of the superconducting ground state present at the (111)LaAlO$_3$/SrTiO$_3$ interface. The superconducting transition is consistent with a Berezinskii-Kosterlitz-Thouless transition and its 2D nature is further corroborated by the anisotropy of the critical magnetic field, as calculated by Tinkham. The estimated superconducting layer thickness and coherence length are 10 nm and 60 nm, respectively. The results of this work provide a new platform to clarify the microscopic details of superconductivity at LaAlO$_3$/SrTiO$_3$ interfaces, in particular in what concerns the link with orbital symmetry.Comment: 4 pages, 4 figure

Probing dynamics of an electron-spin ensemble via a superconducting resonator

We study spin relaxation and diffusion in an electron-spin ensemble of nitrogen impurities in diamond at low temperature (0.25-1.2 K) and polarizing magnetic field (80-300 mT). Measurements exploit mode- and temperature-dependent coupling of hyperfine-split sub-ensembles to the resonator. Temperature-independent spin linewidth and relaxation time suggest that spin diffusion limits spin relaxation. Depolarization of one sub-ensemble by resonant pumping of another indicates fast cross-relaxation compared to spin diffusion, with implications on use of sub-ensembles as independent quantum memories.Comment: 5 pages, 5 figures, and Supplementary Information (2 figures

The application of fluorescence techniques in meningioma surgery-a review

Surgical resections of meningiomas, the most common intracranial tumor in adults, can only be curative if radical resection is achieved. Potentially, the extent of resection could be improved, especially in complex and/or high-grade meningiomas by fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA), indocyanine green (ICG), or fluorescein. This review aims to summarize and evaluate these fluorescence-guided meningioma surgery techniques. PubMed and Embase were searched for relevant articles. Additionally, we checked reference lists for further studies. Forty-eight articles were included in the final analysis. 5-ALA fluoresced with varying sensitivity and selectivity in meningiomas and in invaded bone and dura mater. Although ICG was mainly applied for video angiography, one report shows tumor fluorescence 18-28 h post-ICG injection. Lastly, the use of fluorescein could aid in the identification of tumor remnants; however, detection of dural tail is highly questionable. Fluorescence-guided meningioma surgery should be a reliable, highly specific, and sensitive technique. Despite numerous studies reporting the use of fluorescent dyes, currently, there is no evidence that these tools improve the radical resection rate and long-term recurrence-free outcome in meningioma surgery without neurological deficits. Evidence regarding the effectiveness and increased safety of resection after the application of these fluorophores is currently lacking. Future research should focus on the development of a meningioma-targeted, highly sensitive, and specific fluorophore

Pure cervical radiculopathy due to spontaneous spinal epidural haematoma (SSEH): report of a case solved conservatively

Introduction: Spontaneous spinal epidural haematoma (SSEH) is widely recognised throughout the literature as a cause of myelopathy, radicular compression being very rarely reported. Surgical management is almost always recommended, especially in the cases of spinal cord compression. Conservative treatment is reported as a curiosity and only in the case of spontaneous improvement. This report presents the particular case of a 64-year-old patient undergoing anticoagulant therapy that had a cervical radiculopathy due to a SSEH confirmed by MRI. The patient improved spontaneously and symptoms were solved with unconventional conservative treatment and without stopping the anticoagulant therapy. Conclusions: Spontaneous epidural haematoma must be kept in mind when patients undergoing anticoagulant therapy have a sudden onset of cervicobrachialgia. Even though most spinal surgeons advocate surgical treatment, a conservative approach may lead to a complete recovery and may be considered as a good option in the case of radicular involvement. Discontinuation of the anticoagulant therapy may not always be needed, especially when the clinical syndrome improves spontaneously

Insights from the supplementary motor area syndrome in balancing movement initiation and inhibition

The supplementary motor area syndrome is a characteristic neurosurgical syndrome that can occur after unilateral resection of the supplementary motor area. Clinical symptoms may vary from none to a global akinesia, predominantly on the contralateral side, with preserved muscle strength, and mutism. A remarkable feature is that these symptoms completely resolve within weeks to months, leaving only a disturbance in alternating bimanual movements. In this review we give an overview of the old and new insights from the supplementary motor area syndrome and extrapolate these findings to seemingly unrelated diseases and symptoms such as Parkinson’s disease and tics. Furthermore, we integrate findings from lesion, stimulation and functional imaging studies to provide insight in the motor function of the supplementary motor area

Isotope effects in underdoped cuprate superconductors: a quantum phenomenon

We show that the unusual doping dependence of the isotope effects on transition temperature and zero temperature in - plane penetration depth naturally follows from the doping driven 3D-2D crossover, the 2D quantum superconductor to insulator transition (QSI) in the underdoped limit and the change of the relative doping concentration upon isotope substitution. Close to the QSI transition both, the isotope coefficient of transition temperature and penetration depth approach the coefficient of the relative dopant concentration, and its divergence sets the scale. These predictions are fully consistent with the experimental data and imply that close to the underdoped limit the unusual isotope effect on transition temperature and penetration depth uncovers critical phenomena associated with the quantum superconductor to insulator transition in two dimensions.Comment: 6 pages, 3 figure

Cost-effectiveness of medically assisted reproduction or expectant management for unexplained subfertility:when to start treatment?

STUDY QUESTION Over a time period of 3 years, which order of expectant management (EM), IUI with ovarian stimulation (IUI-OS) and IVF is the most cost-effective for couples with unexplained subfertility with the female age below 38 years? SUMMARY ANSWER If a live birth is considered worth Euro32 000 or less, 2 years of EM followed by IVF was the most cost-effective, whereas above Euro32 000 this was 1 year of EM, 1 year of IUI-OS and then 1 year of IVF. WHAT IS KNOWN ALREADY IUI-OS and IVF are commonly used fertility treatments for unexplained subfertility although many couples can conceive naturally, as no identifiable barrier to conception could be found by definition. Few countries have guidelines on when to proceed with medically assisted reproduction (MAR), mostly based on the expected probability of live birth after treatment, but there is a lack of evidence to support the strategies proposed by these guidelines. The increased uptake of IUI-OS and IVF over the past decades and costs related to reimbursement of these treatments are pressing concerns to health service providers. For MAR to remain affordable, sustainable and a responsible use of public funds, guidance is needed on the cost-effectiveness of treatment strategies for unexplained subfertility, including EM. STUDY DESIGN, SIZE, DURATION We developed a decision analytic Markov model that follows couples with unexplained subfertility of which the woman is under 38 years of age for a time period of 3 years from completion of the fertility workup onwards. We divided the time axis of 3 years into three separate periods, each comprising 1 year. The model was based on contemporary evidence, most notably the dynamic prediction model for natural conception, which was combined with MAR treatment effects from a network meta-analysis on randomized controlled trials. We changed the order of options for managing unexplained subfertility for the 1 year periods to yield five different treatment policies in total: IVF-EM-EM (immediate IVF), EM-IVF-EM (delayed IVF), EM-EM-IVF (postponed IVF), IUIOS-IVF-EM (immediate IUI-OS) and EM-IUIOS-IVF (delayed IUI-OS). PARTICIPANTS/MATERIALS, SETTING, METHODS The main outcomes per policy over the 3-year period were the probability of live birth, the average treatment and delivery costs, the probability of multiple pregnancy, the incremental cost-effectiveness ratio (ICER) and finally, which policy yields the highest net benefit in which costs for a policy were deducted from the health effects, i.e. live births gained. We chose the Dutch societal perspective, but the model can be easily modified for other locations or other perspectives. The probability of live birth after EM was taken from the dynamic prediction model for natural conception and updated for Years 2 and 3. The relative effects of IUI-OS and IVF in terms of odds ratios, taken from the network meta-analysis, were applied to the probability of live birth after EM. We applied standard discounting procedures for economic analyses for Years 2 and 3. The uncertainty around effectiveness, costs and other parameters was assessed by probabilistic sensitivity analysis in which we drew values from distributions and repeated this procedure 20 000 times. In addition, we changed model assumptions to assess their influence on our results. MAIN RESULTS AND THE ROLE OF CHANCE From IVF-EM-EM to EM-IUIOS-IVF, the probability of live birth varied from approximately 54-64% and the average costs from approximately Euro4000 to Euro9000. The policies IVF-EM-EM and EM-IVF-EM were dominated by EM-EM-IVF as the latter yielded a higher cumulative probability of live birth at a lower cost. The policy IUIOS-IVF-EM was dominated by EM-IUIOS-IVF as the latter yielded a higher cumulative probability of live birth at a lower cost. After removal of policies that were dominated, the ICER for EM-IUIOS-IVF was approximately Euro31 000 compared to EM-EM-IVF. The range of ICER values between the lowest 25% and highest 75% of simulation replications was broad. The net benefit curve showed that when we assume a live birth to be worth approximately Euro20 000 or less, the policy EM-EM-IVF had the highest probability to achieve the highest net benefit. Between Euro20 000 and Euro50 000 monetary value per live birth, it was uncertain whether EM-EM-IVF was better than EM-IUIOS-IVF, with the turning point of Euro32 000. When we assume a monetary value per live birth over Euro50 000, the policy with the highest probability to achieve the highest net benefit was EM-IUIOS-IVF. Results for subgroups with different baseline prognoses showed the same policies dominated and the same two policies that were the most likely to achieve the highest net benefit but at different threshold values for the assumed monetary value per live birth. LIMITATIONS, REASONS FOR CAUTION Our model focused on population level and was thus based on average costs for the average number of cycles conducted. We also based the model on a number of key assumptions. We changed model assumptions to assess the influence of these assumptions on our results. The change in relative effectiveness of IVF over time was found to be highly influential on results and their interpretation. WIDER IMPLICATIONS OF THE FINDINGS EM-EM-IVF and EM-IUIOS-IVF followed by IVF were the most cost-effective policies. The choice depends on the monetary value assigned to a live birth. The results of our study can be used in discussions between clinicians, couples and policy makers to decide on a sustainable treatment protocol based on the probability of live birth, the costs and the limitations of MAR treatment. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the ZonMw Doelmatigheidsonderzoek (80-85200-98-91072). The funder had no role in the design, conduct or reporting of this work. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548). B.W.M. reports consultancy for ObsEva, Merck KGaA and Guerbet and travel and research support from ObsEva, Merck and Guerbet. TRIAL REGISTRATION NUMBER N/A

Exploring temporal relationships among worrying, anxiety, and somatic symptoms

OBJECTIVES: The role of anxiety symptoms in the development of functional somatic symptoms (FSS) is unknown. Somatic symptoms may be triggered by or give rise to anxiety symptoms. This study aimed to 1) explore interrelationships among within-day worrying, feeling anxious, and somatic symptoms, and 2) investigate the association between these interrelationships and overall level of FSS. METHODS: This study included 767 participants (83% females, mean age 39 years), who were recruited through an online crowdsourcing study in the Dutch general population. Somatic, and anxiety symptoms were reported thrice daily (6-h intervals) for 30 days using electronic diaries. FSS were assessed at baseline (PHQ-15). Temporal relationships among worrying, feeling anxious, and somatic symptoms were modeled using a multilevel vector autoregressive model. RESULTS: We observed large heterogeneity in the within-person interrelationships among worrying, feeling anxious and somatic symptoms. Averaged over participants, higher-than-usual somatic symptoms were associated with increases in levels of worrying six hours later (B = 0.017, 95% CI [0.006, 0.027]). At the between-person level, FSS levels predicted the persistence of feeling anxious (B = 0.230 95% CI [0.105, 0.350]) and the carry-over of worrying to feeling anxious over six-hours (B = 0.159, 95% CI [0.031, 0.283]). CONCLUSIONS: In contrast to what we expected, higher levels of somatic symptoms over multiple weeks were associated with the persistence and carry-over of within-day anxiety-related symptoms. One within-person association between psychological and somatic symptoms during the day was observed, suggesting that, over a time span of 6-h, anxiety symptoms relate to somatic symptoms only in a minority of people from the general population

Anomalous superconducting state gap size versus Tc behavior in underdoped Bi_2Sr_2Ca_1-xDy_xCu_2O_8+d

We report angle-resolved photoemission spectroscopy measurements of the excitation gap in underdoped superconducting thin films of Bi_2Sr_2Ca_{1-x}Dy_xCu_2O_{8+d}. As Tc is reduced by a factor of 2 by underdoping, the superconducting state gap \Delta does not fall proportionally, but instead stays constant or increases slightly, in violation of the BCS mean-field theory result. The different doping dependences of \Delta and kT_c indicate that they represent different energy scales. The measurements also show that \Delta is highly anisotropic and consistent with a d_{x^2-y^2} order parameter, as in previous studies of samples with higher dopings. However, in these underdoped samples, the anisotropic gap persists well above T_c. The existence of a normal state gap is related to the failure of \Delta to scale with T_c in theoretical models that predict pairing without phase coherence above T_c.Comment: 10 pages, 4 postscript figures, revtex forma