Terahertz wave transmission in flexible polystyrene-lined hollow metallic waveguides for the 2.5-5 THz band.

A low-loss and low-dispersive optical-fiber-like hybrid HE11 mode is developed within a wide band in metallic hollow waveguides if their inner walls are coated with a thin dielectric layer. We investigate terahertz (THz) transmission losses from 0.5 to 5.5 THz and bending losses at 2.85 THz in a polystyrene-lined silver waveguides with core diameters small enough (1 mm) to minimize the number of undesired modes and to make the waveguide flexible, while keeping the transmission loss of the HE11 mode low. The experimentally measured loss is below 10 dB/m for 2 < ? < 2.85 THz (∼4-4.5 dB/m at 2.85 THz) and it is estimated to be below 3 dB/m for 3 < ? < 5 THz according to the numerical calculations. At ∼1.25 THz, the waveguide shows an absorption peak of ∼75 dB/m related to the transition between the TM11-like mode and the HE11 mode. Numerical modeling reproduces the measured absorption spectrum but underestimates the losses at the absorption peak, suggesting imperfections in the waveguide walls and that the losses can be reduced further. © 2013 Optical Society of America

Treatment delays in paediatric dento-alveolar trauma at a tertiary referral hospital

Background: Paediatric dento-alveolar trauma is a common event. Delays in treatment can have adverse effects on long term outcomes and the aim of this study was to quantify the treatment delays in paediatric dento-alveolar trauma in a tertiary referral hospital. Methods: All cases of paediatric dento-alveolar trauma over a two-year period from July 2000 to June 2002 were identified and the charts were reviewed retrospectively. All children presenting the emergency department with dento-alveolar trauma within 48 hours of injury during the time period were included. Results: Forty-three patients were identified. The average age was 5.51 years, though there was a bias towards one and two year olds. Males were injured 1.5 times more frequently than females. There was an average delay of 9.6 hours between injury and treatment for all patients. Transit time from outside practitioners to hospital and waiting times in hospital made up the greatest delays. Children injured an average of 2.37 teeth and only 14 per cent were uncomplicated crown fractures. Conclusions: Children who present to children's hospitals for treatment of dento-alveolar trauma have more severe injuries than those treated elsewhere. They have large but potentially reducible delays between injury and treatment

Saleability of Anti-malarials in Private Drug Shops in Muheza, Tanzania: A Baseline study in an era of assumed Artemisinin Ccombination Therapy (ACT).

Artemether-lumefantrine (ALu) replaced sulphadoxine-pymimethamine (SP) as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT) is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant women depend on SP for Intermittent Preventive Treatment (IPTp) during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform a baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. All drug shops selling prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. All surveyed drug shops illicitly sold SP and quinine (QN), and legally amodiaquine (AQ). Calculated monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local brands of SP accounted for 74% of sales volume, compared to AQ (13%), QN (11%) and ACT (2%). In community practice, the saleability of ACT was negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated in the national anti-malarial policy. It is a major reason for concern that such drug-pressure in the community equals de facto intermittent presumptive treatment. In an area where SP drug resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp strategy. Further studies are recommended to find out barriers for ACT utilization and preference for self-medication and to train private drug dispensers

The spectrum of cardiovascular complications related to immune-checkpoint inhibitor treatment : Including myocarditis and the new entity of non inflammatory left ventricular dysfunction.

BACKGROUND: The full range of cardiovascular complications related to the use of Immune checkpoint inhibitors (ICI) is not fully understood. We aim to describe the spectrum of cardiovascular adverse events (cvAEs) by presenting our real-world experience of the diagnosis and management of these complications. METHODS: Two thousand six hundred and forty-seven (2647) patients were started on ICI treatment between 2014 and 2020. Data from 110 patients referred to the cardio-oncology service with a suspected cvAE was collected prospectively and analysed. RESULTS: Eighty-nine patients (3.4%) were confirmed to have cvAEs while on ICI therapy. Myocarditis was the most frequent event (33/89), followed by tachyarrhythmia (27/89), non-inflammatory left ventricular dysfunction (NILVD) (15/89) and pericarditis (7/89). Results from myocarditis and non-inflammatory left ventricular dysfunction cohorts were compared. Myocarditis and NILVD showed significant differences in respect toof troponin elevation, cardiac magnetic resonance abnormalities and ventricular function. Dual ICI therapy and other immune related adverse events were more frequently associated with myocarditis than NILVD. There was a significant difference in the median time from starting ICI treatment to presentation with myocarditis versus NILVD (12 vs 26 weeks p = 0.049). Through early recognition of myocarditis, prompt treatment with steroids and interruption of ICI, there were no cardiovascular in-hospital deaths. NILVD did not require steroid treatment and ICI could be restarted safely. CONCLUSIONS: The full spectrum of cardiovascular complications in patients with immune checkpoint inhibitors is much broader than initially described. Myocarditis remains the most frequent cvAE related to ICI treatment. A novel type of myocardial injury was observed and defined as Atrial tachyarrhythmias and NILVD were also frequent in this cohort. NILVD has a This differs fromdifferent presentation from ICI-related myocarditis, mainly usually presenting afterby the lack of inflammatory features on CMR and biomarkers and a later presentation in time

Studying Cat (Felis catus) Diabetes: Beware of the Acromegalic Imposter

Naturally occurring diabetes mellitus (DM) is common in domestic cats (Felis catus). It has been proposed as a model for human Type 2 DM given many shared features. Small case studies demonstrate feline DM also occurs as a result of insulin resistance due to a somatotrophinoma. The current study estimates the prevalence of hypersomatotropism or acromegaly in the largest cohort of diabetic cats to date, evaluates clinical presentation and ease of recognition. Diabetic cats were screened for hypersomatotropism using serum total insulin-like growth factor-1 (IGF-1; radioimmunoassay), followed by further evaluation of a subset of cases with suggestive IGF-1 (>1000 ng/ml) through pituitary imaging and/ or histopathology. Clinicians indicated pre-test suspicion for hypersomatotropism. In total 1221 diabetic cats were screened; 319 (26.1%) demonstrated a serum IGF-1>1000 ng/ml (95% confidence interval: 23.6-28.6%). Of these cats a subset of 63 (20%) underwent pituitary imaging and 56/63 (89%) had a pituitary tumour on computed tomography; an additional three on magnetic resonance imaging and one on necropsy. These data suggest a positive predictive value of serum IGF-1 for hypersomatotropism of 95% (95% confidence interval: 90-100%), thus suggesting the overall hypersomatotropism prevalence among UK diabetic cats to be 24.8% (95% confidence interval: 21.2-28.6%). Only 24% of clinicians indicated a strong pre-test suspicion; most hypersomatotropism cats did not display typical phenotypical acromegaly signs. The current data suggest hypersomatotropism screening should be considered when studying diabetic cats and opportunities exist for comparative acromegaly research, especially in light of the many detected communalities with the human disease

Capture the fracture: a best practice framework and global campaign to break the fragility fracture cycle

Summary The International Osteoporosis Foundation (IOF) Capture the Fracture Campaign aims to support implementation of Fracture Liaison Services (FLS) throughout the world. Introduction FLS have been shown to close the ubiquitous secondary fracture prevention care gap, ensuring that fragility fracture sufferers receive appropriate assessment and intervention to reduce future fracture risk. Methods Capture the Fracture has developed internationally endorsed standards for best practice, will facilitate change at the national level to drive adoption of FLS and increase awareness of the challenges and opportunities presented by secondary fracture prevention to key stakeholders. The Best Practice Framework (BPF) sets an international benchmark for FLS, which defines essential and aspirational elements of service delivery. Results The BPF has been reviewed by leading experts from many countries and subject to beta-testing to ensure that it is internationally relevant and fit-for-purpose. The BPF will also serve as a measurement tool for IOF to award ‘Capture the Fracture Best Practice Recognition’ to celebrate successful FLS worldwide and drive service development in areas of unmet need. The Capture the Fracture website will provide a suite of resources related to FLS and secondary fracture prevention, which will be updated as new materials become available. A mentoring programme will enable those in the early stages of development of FLS to learn from colleagues elsewhere that have achieved Best Practice Recognition. A grant programme is in development to aid clinical systems which require financial assistance to establish FLS in their localities. Conclusion Nearly half a billion people will reach retirement age during the next 20 years. IOF has developed Capture the Fracture because this is the single most important thing that can be done to directly improve patient care, of both women and men, and reduce the spiralling fracture-related care costs worldwide.</p

Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status.

We evaluated homologous recombination deficient (HRD) phenotypes in epithelial ovarian cancer (EOC) considering BRCA1, BRCA2, and RAD51C in a large well-annotated patient set. We evaluated EOC patients for germline deleterious mutations (n = 899), somatic mutations (n = 279) and epigenetic alterations (n = 482) in these genes using NGS and genome-wide methylation arrays. Deleterious germline mutations were identified in 32 (3.6%) patients for BRCA1, in 28 (3.1%) for BRCA2 and in 26 (2.9%) for RAD51C. Ten somatically sequenced patients had deleterious alterations, six (2.1%) in BRCA1 and four (1.4%) in BRCA2. Fifty two patients (10.8%) had methylated BRCA1 or RAD51C. HRD patients with germline or somatic alterations in any gene were more likely to be high grade serous, have an earlier diagnosis age and have ovarian and/or breast cancer family history. The HRD phenotype was most common in high grade serous EOC. Identification of EOC patients with an HRD phenotype may help tailor specific therapies.This work was supported by National Institutes of Health grants R01-CA122443, P50-CA136393, P30-CA15083, and the Fred C. and Katherine B. Andersen Foundation. We thank Gary Kenney, M.D. for pathology review of tumor tissue. We thank Craig Luccarini, Caroline Baynes from University of Cambridge for assisting our sample sequencing

Cerebrospinal fluid sodium rhythms

Background: Cerebrospinal fluid (CSF) sodium levels have been reported to rise during episodic migraine. Since migraine frequently starts in early morning or late afternoon, we hypothesized that natural sodium chronobiology may predispose susceptible persons when extracellular CSF sodium increases. Since no mammalian brain sodium rhythms are known, we designed a study of healthy humans to test if cation rhythms exist in CSF. Methods: Lumbar CSF was collected every ten minutes at 0.1 mL/min for 24 h from six healthy participants. CSF sodium and potassium concentrations were measured by ion chromatography, total protein by fluorescent spectrometry, and osmolarity by freezing point depression. We analyzed cation and protein distributions over the 24 h period and spectral and permutation tests to identify significant rhythms. We applied the False Discovery Rate method to adjust significance levels for multiple tests and Spearman correlations to compare sodium fluctuations with potassium, protein, and osmolarity. Results: The distribution of sodium varied much more than potassium, and there were statistically significant rhythms at 12 and 1.65 h periods. Curve fitting to the average time course of the mean sodium of all six subjects revealed the lowest sodium levels at 03.20 h and highest at 08.00 h, a second nadir at 09.50 h and a second peak at 18.10 h. Sodium levels were not correlated with potassium or protein concentration, or with osmolarity. Conclusion: These CSF rhythms are the first reports of sodium chronobiology in the human nervous system. The results are consistent with our hypothesis that rising levels of extracellular sodium may contribute to the timing of migraine onset. The physiological importance of sodium in the nervous system suggests that these rhythms may have additional repercussions on ultradian functions

Neurobehavioral Mechanisms of Temporal Processing Deficits in Parkinson's Disease

Parkinson's disease (PD) disrupts temporal processing, but the neuronal sources of deficits and their response to dopamine (DA) therapy are not understood. Though the striatum and DA transmission are thought to be essential for timekeeping, potential working memory (WM) and executive problems could also disrupt timing.The present study addressed these issues by testing controls and PD volunteers 'on' and 'off' DA therapy as they underwent fMRI while performing a time-perception task. To distinguish systems associated with abnormalities in temporal and non-temporal processes, we separated brain activity during encoding and decision-making phases of a trial. Whereas both phases involved timekeeping, the encoding and decision phases emphasized WM and executive processes, respectively. The methods enabled exploration of both the amplitude and temporal dynamics of neural activity. First, we found that time-perception deficits were associated with striatal, cortical, and cerebellar dysfunction. Unlike studies of timed movement, our results could not be attributed to traditional roles of the striatum and cerebellum in movement. Second, for the first time we identified temporal and non-temporal sources of impaired time perception. Striatal dysfunction was found during both phases consistent with its role in timekeeping. Activation was also abnormal in a WM network (middle-frontal and parietal cortex, lateral cerebellum) during encoding and a network that modulates executive and memory functions (parahippocampus, posterior cingulate) during decision making. Third, hypoactivation typified neuronal dysfunction in PD, but was sometimes characterized by abnormal temporal dynamics (e.g., lagged, prolonged) that were not due to longer response times. Finally, DA therapy did not alleviate timing deficits.Our findings indicate that impaired timing in PD arises from nigrostriatal and mesocortical dysfunction in systems that mediate temporal and non-temporal control-processes. However, time perception impairments were not improved by DA treatment, likely due to inadequate restoration of neuronal activity and perhaps corticostriatal effective-connectivity