The poor stickiness of silicate dust grains is a major obstacle to the formation of rocky planetesimals. In this study, we examine the possibility that silicate grains with an organic mantle, which ...we call Organic-mantled Grains (OMGs), form planetesimals through direct coagulation. Organic mantles are commonly found in interplanetary dust particles, and laboratory experiments show that they are softer than silicates, in particular in warm environments. This, combined with the theory of particle adhesion, implies that OMGs are stickier than bare silicate grains. Because organic mantles can survive up to 400 K, silicate grains inside the water snow line in protoplanetary disks can in principle hold such mantles. We construct a simple grain adhesion model to estimate the threshold collision velocity below which aggregates of OMGs can grow. The model shows that aggregates of 0.1 m-sized OMGs can overcome the fragmentation barrier in protoplanetary disks if the mantles are as thick as those in interplanetary dust particles and if the temperature is above ∼200 K. We use this adhesion model to simulate the global evolution of OMG aggregates in the inner part of a protoplanetary disk, demonstrating that OMG aggregates can indeed grow into planetesimals under favorable conditions. Because organic matter is unstable at excessively high temperatures, rocky planetesimal formation by the direct sticking of OMGs is expected to occur in a disk annulus corresponding to the temperature range ∼200-400 K. The organic-rich planetesimals may grow into carbon-poor rocky planetesimals by accreting a large amount of carbon-poor chondrules.
The standard of care for first-line treatment of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) is combination treatment with platinum, 5-FU and cetuximab (PFE). ...However, this regimen requires hospitalization to ensure proper hydration and continuous infusion of 5-FU, and causes severe nausea and anorexia. We evaluated the efficacy and safety of paclitaxel, carboplatin and cetuximab (PCE) as first-line treatment in patients with R/M SCCHN.
Eligibility criteria included recurrent and/or metastatic, histologically proven SCC of the oropharynx, oral cavity, hypopharynx or larynx; PS 0-1; adequate organ function; no suitable local therapy for R/M SCCHN; and no prior systemic chemotherapy for R/M SCCHN. Chemotherapy consisted of paclitaxel 100mg/m2 on days 1, 8; carboplatin area under the blood concentration-time curve 2.5 on days 1, 8, repeated every 3weeks for up to 6 cycles; and cetuximab at an initial dose of 400mg/m2, followed by 250mg/m2 weekly until disease progression or unacceptable toxicities. Primary end point was overall response rate. Secondary end points were safety, treatment completion rate, progression-free survival, overall survival, and clinical benefit rate. Planned sample size was 45 patients.
Forty-seven subjects were accrued from July 2013 to October 2014. Of 45 evaluable, 40 were male; median age was 63years; Eastern Cooperative Oncology Group Performance Status was 0/1 in 23/22 cases; site was the hypopharynx/oropharynx/oral cavity/larynx in 17/11/10/7 cases; and 36/9 cases were smokers/nonsmokers, respectively. Overall response rate, the primary end point, was 40%. Median overall survival was 14.7months and progression-free survival was 5.2months. Grade 3/4 adverse events included neutropenia (68%), skin reaction (15%), fatigue (9%) and febrile neutropenia (9%). A potentially treatment-related death occurred in one patient with intestinal pneumonia.
The PCE regimen shows promising activity with acceptable toxicity in the outpatient clinic. Further studies are needed to compare PCE with PFE in this population.
UMIN000010507.
The purpose of this study was to evaluate the efficacy of superselective cisplatin infusion with concomitant radiotherapy (RADPLAT) for previously untreated patients with the squamous cell carcinoma ...of maxillary sinus (SCC-MS).
Between 1999 and 2010, 54 patients were given superselective intra-arterial infusions of cisplatin (100-120 mg m(-2) per week) with simultaneous intra-venous infusions of thiosulfate to neutralise cisplatin toxicity and conventional radiotherapy (65-70 Gy).
One patient (1.9%) was diagnosed with T2, 14 (25.9%) with T3, 27 (50%) with T4a, and 12 (22.2%) with T4b disease. Lymph-node involvement was present in 12 patients (22.2%). During the median follow-up period of 6.4 years, the 5-year local progression-free and overall survival rates were 65.8 and 67.9% for all patients, respectively. No patient died as a result of treatment toxicity or experienced a cerebrovascular accident. Osteonecrosis (n=5), brain necrosis (n=1), and ocular/visual problems (n=14) were observed as late adverse reactions.
We have shown excellent overall survival and local progression-free rate in SCC-MS patients treated by RADPLAT with acceptable rates of acute and late toxicity. A multi-institutional trial is needed to prove that this strategy is a feasible and effective approach for the treatment of SCC-MS.
As the use of monitoring technology is attracting attention in the field of maintenance and management of infrastructure, the Research Association for Infrastructure Monitoring System (RAIMS) ...participated in the SIP (Cross-ministerial Strategic Innovation Promotion Program, FY2014-2018) of the Cabinet Office and compiled information on monitoring technology effective in various situations such as inspection, diagnosis, repair, and reinforcement of infrastructure. JSCE had the results of this initiative evaluated by the Subcommittee for the Promotion of New Technology Application of the General Committee on Infrastructure Maintenance, re-edited them with on-site implementation in mind, and published them as new guidelines for the on-site implementation of monitoring technology for engineers engaged in maintenance and management. This paper presents an overview of these guidelines.
This study aimed to predict eosinophilic chronic rhinosinusitis prognosis by investigating changes in the blood eosinophil count and other disease biomarkers after surgery.
Blood eosinophil numbers ...and serum interleukin-5 levels were measured in 22 eosinophilic chronic rhinosinusitis patients before and after functional endoscopic sinus surgery, and compared with equivalent measures in non-eosinophilic chronic rhinosinusitis patients and chronic rhinosinusitis without polyps patients. Differences between well-controlled eosinophilic chronic rhinosinusitis patients and those who experienced recurrence were also assessed.
Blood eosinophil numbers and serum interleukin-5 level decreased after surgery in eosinophilic chronic rhinosinusitis patients. In this patient group, blood eosinophil counts before surgery were significantly higher in patients who experienced recurrence (825.7 ± 26.1 vs 443.9 ± 76.6 cells/μl, p < 0.05), and decreased significantly after surgery (825.7 ± 26.1 vs 76.7 ± 25.8 cells/μl, p < 0.05).
Blood eosinophil numbers may reflect disease severity in eosinophilic chronic rhinosinusitis patients and their prognosis after surgery.
For the assessment of the treatment response in non-surgical treatment, tumor blood flow provides the functional information of the tumor which is different from the morphological information such as ...tumor volume. The purpose of this study was to evaluate the diagnostic value of tumor blood flow values obtained by pseudocontinuous arterial spin-labeling in patients with head and neck squamous cell carcinoma.
Forty-one patients with head and neck squamous cell carcinoma were evaluated by using pseudocontinuous arterial spin-labeling. Quantitative tumor blood flow was calculated at the pretreatment and the early treatment periods in all the patients, and the percentage change of tumor blood flow between the two was calculated. At the early treatment period, based on their tumor volume reduction rate, we divided the patients into stable disease and partial response groups for a subgroup analysis. The local control or failure was confirmed either by histopathology or by radiologic evaluation within the follow-up.
Pretreatment tumor blood flow in patients in the failure group was significantly lower than that in patients in the local control group. In the subgroup analysis of patients with stable disease, the percentage change of tumor blood flow was significantly larger (due to the tumor blood flow increase from pretreatment value) in the local control group than in the failure group. In addition, in patients with a partial response, the percentage change of tumor blood flow was significantly smaller (due to the tumor blood flow decrease from the pretreatment value) in the local control group than in the failure group. The accuracy for determination of the local control group or the failure group in pretreatment tumor blood flow was 0.83 and that in the combination use of the percentage change of tumor blood flow and tumor volume in the early treatment period was 0.93.
Tumor blood flow obtained by pseudocontinuous arterial spin-labeling can be useful for the determination of local control. The combined use of the percentage change of tumor blood flow and tumor volume had particularly high diagnostic accuracy.
Meningococcal disease by serogroup B has been a public health problem in Brazil in the last decades. The Brazilian Oswaldo Cruz Foundation has been working to develop a vaccine with detergent-treated ...outer membrane vesicles (OMV) and detoxified endotoxin (dLOS) from Neisseria meningitidis serogroup B prevalent strains. A phase I study, enrolling 26 adults (18–44 years of age) was performed using experimental vaccines combining B components and aluminum hydroxide as adjuvant. It was a dose escalation study testing vaccines made of 25, 50, and 100 µg OMV protein/mL (sum of both strains) and dLOS in half amount of total protein concentration, with three doses given two months apart. Adverse events were mild/moderate with frequency increasing with the amount of antigens. Pain in the site of injection was the most frequent reaction in all doses, reported in more than the 85% across vaccine groups. Considering all injections, cephalea was the most common systemic adverse event, detected in 11.1%, 17.2% and 32.1%, respectively with doses of 12.5 μg, 25 μg and 50 μg. High titers of total IgG (ELISA) were observed for the vaccine components before vaccination. Protective levels of bactericidal antibodies (titer ≥1:4) for both vaccine strains were also present. Considering a 4-fold increase of IgG titers compared to pre-immune values (seroconversion), 50%-70% of those who received intermediate and highest doses of antigens presented satisfactory response for OMV of N44/89 strain. The lowest dose vaccine induced no seroconversion for strain N44/89, and 11% for strain N603/95. For the three vaccines doses, 25% of seroconversion, in total IgG against LOS, was observed. Increased antibody bactericidal activity was observed for both strains in higher antigen concentrations. For IgG against LOS, all vaccine formulations showed 25% of seroconversion. In conclusion, MenB-Bio experimental vaccines were well tolerated and immunogenic, thus allowing phase II studies.
Background
There is growing awareness of the coexistence of Alzheimer's disease and cerebrovascular disease (AD+CVD), however, due to lack of well‐defined criteria and treatment guidelines AD+CVD may ...be underdiagnosed in Asia.
Methods
Sixteen dementia specialists from nine Asia Pacific countries completed a survey in September 2014 and met in November 2014 to review the epidemiology, diagnosis and treatment of AD+CVD in Asia. A consensus was reached by discussion, with evidence provided by published studies when available.
Results
AD accounts for up to 60% and AD+CVD accounts for 10‐20% of all dementia cases in Asia. The reasons for underdiagnosis of AD+CVD include lack of awareness as a result of a lack of diagnostic criteria, misdiagnosis as vascular dementia or AD, lack of diagnostic facilities, resource constraints and cost of investigations. There is variability in the tools used to diagnose AD+CVD in clinical practice. Diagnosis of AD+CVD should be performed in a stepwise manner of clinical evaluation followed by neuroimaging. Dementia patients should be assessed for cognition, behavioural and psychological symptoms, functional staging and instrumental activities of daily living. Neuroimaging should be performed using computed tomography or magnetic resonance imaging. The treatment goals are to stabilize or slow progression as well as to reduce behavioural and psychological symptoms, improve quality of life and reduce disease burden. First‐line therapy is usually an acetylcholinesterase inhibitor such as donepezil.
Conclusion
AD+CVD is likely to be under‐recognised in Asia. Further research is needed to establish the true prevalence of this treatable and potentially preventable disease.
Zinc plays an important role in many biological processes. Reduced zinc levels have been found in chronic rhinosinusitis (CRS) patients, however, its role in the pathophysiology of this disease ...remains unknown. This study examined zinc levels in the serum, mucus and tissue from CRS patients in relation to collagen content and eosinophil infiltration. The effect of zinc depletion on inflammatory cytokine production and collagen synthesis was assessed in vitro.
Zinc levels were determined in serum, mucus and tissue from controls, CRS with (CRSwNP) and without nasal polyps (CRSsNP) patients. Tissue zinc levels, collagen and inflammatory cell infiltration was examined using zinquin assays, immunofluorescence and histology on Tissue Micro Arrays. Cytokine expression and collagen synthesis was evaluated in zinc depleted primary human nasal epithelial cells (HNECs) and primary fibroblasts.
CRSwNP patients showed reduced tissue zinc levels in correlation with a reduction in collagen content, and increased eosinophil numbers. Zinc depletion of HNECs and fibroblasts induced the production of pro-inflammatory cytokines and MUC5AC and reduced collagen secretion.
These results suggest mucosal zinc depletion associates with tissue eosinophilia and collagen depletion in CRSwNP and induces pro-inflammatory cytokine expression and reduction of collagen synthesis in vitro.
In Alzheimer disease (AD), a peculiar regional cerebral blood flow (rCBF) abnormality has been reported in the posterior cingulate gyri and precunei, even at a very early stage. We performed a ...multicenter brain perfusion single-photon emission tomography (SPECT) study to evaluate the discrimination ability of an easy Z-score imaging system (eZIS) with a common normal data base between patients with very early AD at the stage of mild cognitive impairment and age-matched healthy controls.
For a multicenter study, SPECT images of 40 patients with AD and 40 healthy volunteers were acquired from 4 gamma camera systems in 4 different institutions. Systematic differences of SPECT images between gamma cameras were corrected by using conversion maps calculated from the SPECT images of the same brain phantom. Receiver operating characteristic (ROC) analysis was performed to discriminate patients and controls by using a Z-score in the volume of interest (VOI), which had been defined as a region related to AD in subjects other than those in a multicenter study.
Bilateral posterior cingulate gyri, precunei, and parietal cortices were defined as a VOI showing rCBF reduction in very early AD. A new indicator of rCBF abnormality in the VOI provided 86% accuracy for distinction of AD and healthy controls in the multicenter study. The area under the ROC curve was 0.934.
Because an eZIS can use a common normal data base by converting site-specific SPECT data to the core data, the eZIS was useful for automated diagnosis of very early AD in routine studies in multiple institutions.
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