Development and testing of the Active Temperature, Ozone and Moisture Microwave Spectrometer (ATOMMS) cm and mm wavelength occultation instrument

We present initial results from testing a new remote sensing system called the Active Temperature, Ozone and Moisture Microwave Spectrometer (ATOMMS). ATOMMS is designed as a satellite-to-satellite occultation system for monitoring climate. We are developing the prototype instrument for an aircraft to aircraft occultation demonstration. Here we focus on field testing of the ATOMMS instrument, in particular the remote sensing of water by measuring the attenuation caused by the 22 GHz and 183 GHz water absorption lines. Our measurements of the 183 GHz line spectrum along an 820 m path revealed that the AM 6.2 spectroscopic model provdes a much better match to the observed spectrum than the MPM93 model. These comparisons also indicate that errors in the ATOMMS amplitude measurements are about 0.3%. Pressure sensitivity bodes well for ATOMMS as a climate instrument. Comparisons with a hygrometer revealed consistency at the 0.05 mb level, which is about 1% of the absolute humidity. Initial measurements of absorption by the 22 GHz line made along a 5.4 km path between two mountaintops captured a large increase in water vapor similar to that measured by several nearby hygrometers. A storm passage between the two instruments yielded our first measurements of extinction by rain and cloud droplets. Comparisons of ATOMMS 1.5 mm opacity measurements with measured visible opacity and backscatter from a weather radar revealed features simultaneously evident in all three datasets confirming the ATOMMS measurements. The combined ATOMMS, radar and visible information revealed the evolution of rain and cloud amounts along the signal path during the passage of the storm. The derived average cloud water content reached typical continental cloud amounts. These results demonstrated a significant portion of the information content of ATOMMS and its ability to penetrate through clouds and rain which is critical to its all-weather, climate monitoring capability

The effect of phosphodiesterase-5 inhibitors on cerebral blood flow in humans: A systematic review.

Agents that augment cerebral blood flow (CBF) could be potential treatments for vascular cognitive impairment. Phosphodiesterase-5 inhibitors are vasodilating drugs established in the treatment of erectile dysfunction (ED) and pulmonary hypertension. We reviewed published data on the effects of phosphodiesterase-5 inhibitors on CBF in adult humans. A systematic review according to PRISMA guidelines was performed. Embase, Medline and Cochrane Library Trials databases were searched. Sixteen studies with 353 participants in total were retrieved. Studies included healthy volunteers and patients with migraine, ED, type 2 diabetes, stroke, pulmonary hypertension, Becker muscular dystrophy and subarachnoid haemorrhage. Most studies used middle cerebral artery flow velocity to estimate CBF. Few studies employed direct measurements of tissue perfusion. Resting CBF velocity was unaffected by phosphodiesterase-5 inhibitors, but cerebrovascular regulation was improved in ED, pulmonary hypertension, diabetes, Becker's and a group of healthy volunteers. This evidence suggests that phosphodiesterase-5 inhibitors improve responsiveness of the cerebral vasculature, particularly in disease states associated with an impaired endothelial dilatory response. This supports the potential therapeutic use of phosphodiesterase-5 inhibitors in vascular cognitive impairment where CBF is reduced. Further studies with better resolution of deep CBF are warranted. The review is registered on the PROSPERO database (registration number CRD42016029668)

High efficacy and low toxicity of weekly docetaxel given as first-line treatment for metastatic breast cancer

Background: Docetaxel is one of the most effective antitumor agents currently available for the treatment of metastatic breast cancer (MBC). This phase II multicenter study prospectively analyzed the efficacy and toxicity of docetaxel given on a weekly schedule as first-line treatment of metastatic breast cancer. Patients and Methods: All patients received docetaxel, 35 mg/m(2) weekly for 6 weeks, followed by 2 weeks of rest. Subsequent cycles ( 3 weeks of treatment, 2 weeks of rest) were given until a maximum of 5 cycles or disease progression. Premedication consisted of 8 mg dexamethasone intravenously 30 min prior to the infusion of docetaxel. Results: Fifty-four patients at a median age of 58 years with previously untreated MBC were included in the study. A median of 10 doses ( median cumulative dose 339 mg/m(2)) was administered ( range: 2 - 18). The overall response rate was 48.1% ( 95% CI: 34 - 61%, intent-to-treat). Median survival was 15.8 months and median time to progression was 5.9 months ( intent-to-treat). Hematological toxicity was mild with absence of neutropenia-related complications. Grade 3 neutropenia was observed in 3.7% of patients and grade 3 and 4 anemia was observed in 5.6 and 1.9% of patients, respectively. Conclusion: The weekly administration of docetaxel is highly efficient and safe as first-line treatment for MBC and may serve as an important treatment option specifically in elderly patients and patients with a reduced performance status. Copyright (C) 2005 S. Karger AG, Basel

Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study

$\textbf{Background}$ Psychosis is a common presenting feature in antibody-mediated encephalitis, for which prompt recognition and treatment usually leads to remission. We aimed to investigate whether people with circumscribed schizophrenia-like illnesses have such antibodies—especially antibodies against the N-methyl-D-aspartate receptor (NMDAR)—more commonly than do healthy controls. $\textbf{Methods}$ We recruited patients aged 14–35 years presenting to any of 35 mental health services sites across England with first-episode psychosis, less than 6 weeks of treatment with antipsychotic medication, and a score of 4 or more on at least one selected Positive and Negative Syndrome Scale (PANSS) item. Patients and controls provided venous blood samples. We completed standardised symptom rating scales (PANSS, ACE-III, GAF) at baseline, and tested serum samples for antibodies against NMDAR, LGI1, CASPR2, the GABAA receptor, and the AMPA receptor using live cell-based assays. Treating clinicians assessed outcomes of ICD diagnosis and functioning (GAF) at 6 months. We included healthy controls from the general population, recruited as part of another study in Cambridge, UK. $\textbf{Findings}$ Between Feb 1, 2013, and Aug 31, 2014, we enrolled 228 patients with first-episode psychosis and 105 healthy controls. 20 (9%) of 228 patients had serum antibodies against one or more of the neuronal cell surface antibodies compared with four (4%) of 105 controls (unadjusted odds ratio 2·4, 95% CI 0·8–7·3). These associations remained non-significant when adjusted for current cigarette smoking, alcohol consumption, and illicit drug use. Seven (3%) patients had NMDAR antibodies compared with no controls (p=0·0204). The other antibodies did not differ between groups. Antibody-positive patients had lower PANSS positive, PANSS total, and catatonia scores than did antibody-negative patients. Patients had comparable scores on other PANSS items, ACE-III, and GAF at baseline, with no difference in outcomes at 6 months. $\textbf{Interpretation}$ Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics. Our study suggests that the only way to detect patients with these potentially pathogenic antibodies is to screen all patients with first-episode psychosis at first presentation.Medical Research Counci

Caregiving in multiple sclerosis and quality of life: a meta-synthesis of qualitative research

Objective: The lack of adequate conceptualisation and operationalisation of quality of life (QoL) limits the ability to have a consistent body of evidence to improve QoL research and practice in informal caregiving for people with multiple sclerosis (MS). Thus, we conducted a meta-synthesis of qualitative research to improve the conceptual understanding of the experiences of MS carers and to identify factors that affect carers' QoL. Design: Systematic searches of five electronic databases yielded 17 qualitative studies which were synthesised using the principles of meta-ethnography. Results: The synthesis resulted in nine inter-linking themes: Changes and losses; challenges revolving around MS; caregiving demands; burden of care; future concerns; external stressors; experiences of support; strategies used in managing the caregiving role; and motivating factors. Our findings suggest that MS carers can have both positive and negative experiences which may bring challenges and rewards to the carers. Conclusion: We present a proposed QoL model for MS caregiving which can be used to inform the development of interventions for MS carers to improve their QoL. However, further empirical research is needed to examine the utility of this model and to explore the concept of QoL in MS carers in more detail

Laser treatment in diabetic retinopathy

Diabetic retinopathy is a leading cause of visual impairment and blindness in developed countries due to macular edema and proliferative diabetic retinopathy (PDR). For both complications laser treatment may offer proven therapy: the Diabetic Retinopathy Study demonstrated that panretinal scatter photocoagulation reduces the risk of severe visual loss by >= 50% in eyes with high-risk characteristics. Pan-retinal scatter coagulation may also be beneficial in other PDR and severe nonproliferative diabetic retinopathy (NPDR) under certain conditions. For clinically significant macular edema the Early Treatment of Diabetic Retinopathy Study could show that immediate focal laser photocoagulation reduces the risk of moderate visual loss by at least 50%. When and how to perform laser treatment is described in detail, offering a proven treatment for many problems associated with diabetic retinopathy based on a high evidence level. Copyright (c) 2007 S. Karger AG, Basel

Prevalence and clinical characteristics of serum neuronal cell surface antibodies in first-episode psychosis: a case-control study

$\textbf{Background}$ Psychosis is a common presenting feature in antibody-mediated encephalitis, for which prompt recognition and treatment usually leads to remission. We aimed to investigate whether people with circumscribed schizophrenia-like illnesses have such antibodies—especially antibodies against the N-methyl-D-aspartate receptor (NMDAR)—more commonly than do healthy controls. $\textbf{Methods}$ We recruited patients aged 14–35 years presenting to any of 35 mental health services sites across England with first-episode psychosis, less than 6 weeks of treatment with antipsychotic medication, and a score of 4 or more on at least one selected Positive and Negative Syndrome Scale (PANSS) item. Patients and controls provided venous blood samples. We completed standardised symptom rating scales (PANSS, ACE-III, GAF) at baseline, and tested serum samples for antibodies against NMDAR, LGI1, CASPR2, the GABAA receptor, and the AMPA receptor using live cell-based assays. Treating clinicians assessed outcomes of ICD diagnosis and functioning (GAF) at 6 months. We included healthy controls from the general population, recruited as part of another study in Cambridge, UK. $\textbf{Findings}$ Between Feb 1, 2013, and Aug 31, 2014, we enrolled 228 patients with first-episode psychosis and 105 healthy controls. 20 (9%) of 228 patients had serum antibodies against one or more of the neuronal cell surface antibodies compared with four (4%) of 105 controls (unadjusted odds ratio 2·4, 95% CI 0·8–7·3). These associations remained non-significant when adjusted for current cigarette smoking, alcohol consumption, and illicit drug use. Seven (3%) patients had NMDAR antibodies compared with no controls (p=0·0204). The other antibodies did not differ between groups. Antibody-positive patients had lower PANSS positive, PANSS total, and catatonia scores than did antibody-negative patients. Patients had comparable scores on other PANSS items, ACE-III, and GAF at baseline, with no difference in outcomes at 6 months. $\textbf{Interpretation}$ Some patients with first-episode psychosis had antibodies against NMDAR that might be relevant to their illness, but did not differ from patients without NMDAR antibodies in clinical characteristics. Our study suggests that the only way to detect patients with these potentially pathogenic antibodies is to screen all patients with first-episode psychosis at first presentation.Medical Research Counci

Phase I study of sorafenib combined with radiation therapy and temozolomide as first-line treatment of high-grade glioma.

BACKGROUND: Sorafenib (Sb) is a multiple kinase inhibitor targeting both tumour cell proliferation and angiogenesis that may further act as a potent radiosensitizer by arresting cells in the most radiosensitive cell cycle phase. This phase I open-label, noncontrolled dose escalation study was performed to determine the safety and maximum tolerated dose (MTD) of Sb in combination with radiation therapy (RT) and temozolomide (TMZ) in 17 patients with newly diagnosed high-grade glioma. METHODS: Patients were treated with RT (60 Gy in 2 Gy fractions) combined with TMZ 75 mg m(-2) daily, and Sb administered at three dose levels (200 mg daily, 200 mg BID, and 400 mg BID) starting on day 8 of RT. Thirty days after the end of RT, patients received monthly TMZ (150-200 mg m(-2) D1-5/28) and Sb (400 mg BID). Pharmacokinetic (PK) analyses were performed on day 8 (TMZ) and on day 21 (TMZ&Sb) (Clinicaltrials ID: NCT00884416). RESULTS: The MTD of Sb was established at 200 mg BID. Dose-limiting toxicities included thrombocytopenia (two patients), diarrhoea (one patient) and hypercholesterolaemia (one patient). Sb administration did not affect the mean area under the curve(0-24) and mean Cmax of TMZ and its metabolite 5-amino-imidazole-4-carboxamide (AIC). Tmax of both TMZ and AIC was delayed from 0.75 (TMZ alone) to 1.5 h (combined TMZ/Sb). The median progression-free survival was 7.9 months (95% confidence interval (CI): 5.4-14.55), and the median overall survival was 17.8 months (95% CI: 14.7-25.6). CONCLUSIONS: Although Sb can be combined with RT and TMZ, significant side effects and moderate outcome results do not support further clinical development in malignant gliomas. The robust PK data of the TMZ/Sb combination could be useful in other cancer settings