Microlenses immersed in nematic liquid crystal with electrically controllable focal length

A microlens immersed in a nematic liquid crystal cell has been constructed with avariable focal length which can be controlled by applying an analogue voltage to thenematic liquid crystal. The focal length is -910 ± 30 ? m with no electric field appliedand with an applied field the focal length can be varied from 380 ± 50 to 560 ± 20 ? malthough at present the lens performance is limited by aberrations. A microlens immersed in a nematic liquid crystal cell has been constructed with avariable focal length which can be controlled by applying an analogue voltage to thenematic liquid crystal. The focal length is -910 ± 30 ? m with no electric field appliedand with an applied field the focal length can be varied from 380 ± 50 to 560 ± 20 ? malthough at present the lens performance is limited by aberrations. 12 May 199

Alpha adrenergic modulation on effects of norepinephrine transporter inhibitor reboxetine in five-choice serial reaction time task

The study examined the effects of a norepinephrine transporter (NET) inhibitor reboxetine (RBX) on an attentional performance test. Adult SD rats trained with five-choice serial reaction time task (5-CSRTT) were administered with RBX (0, 3.0 and 10 mg/kg) in the testing day. Alpha-1 adrenergic receptor antagonist PRA and alpha-2 adrenergic receptor antagonist RX821002 were used to clarify the RBX effect. Results revealed that rat received RBX at 10 mg/kg had an increase in the percentage of the correct response and decreases in the numbers of premature response. Alpha-1 adrenergic receptor antagonist Prazosin (PRA) at 0.1 mg/kg reversed the RBX augmented correct responding rate. However, alpha-2 adrenergic receptor antagonist RX821002 at 0.05 and 0.1 mg/kg dose dependently reversed the RBX reduced impulsive responding. Our results suggested that RBX as a norepinephrine transporter inhibitor can be beneficial in both attentional accuracy and response control and alpha-1 and alpha-2 adrenergic receptors might be involved differently

Cumulative Lead Dose and Cognitive Function in Adults: A Review of Studies That Measured Both Blood Lead and Bone Lead

OBJECTIVE: We review empirical evidence for the relations of recent and cumulative lead dose with cognitive function in adults. DATA SOURCES: A systematic search of electronic databases resulted in 21 environmental and occupational studies from 1996 to 2006 that examined and compared associations of recent (in blood) and cumulative (in bone) lead doses with neurobehavioral outcomes. DATA EXTRACTION: Data were abstracted after consideration of exclusion criteria and quality assessment, and then compiled into summary tables. CONCLUSIONS: At exposure levels encountered after environmental exposure, associations with bio-markers of cumulative dose (mainly lead in tibia) were stronger and more consistent than associations with blood lead levels. Similarly, in studies of former workers with past occupational lead exposure, associations were also stronger and more consistent with cumulative dose than with recent dose (in blood). In contrast, studies of currently exposed workers generally found associations that were more apparent with blood lead levels; we speculate that the acute effects of high, recent dose may mask the chronic effects of cumulative dose. There is moderate evidence for an association between psychiatric symptoms and lead dose but only at high levels of current occupational lead exposure or with cumulative dose in environmentally exposed adults

Antitumor Activity of Pembrolizumab in Biomarker-Unselected Patients With Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma: Results From the Phase Ib KEYNOTE-012 Expansion Cohort.

Purpose Treatment with pembrolizumab, an anti-programmed death-1 antibody, at 10 mg/kg administered once every 2 weeks, displayed durable antitumor activity in programmed death-ligand 1 (PD-L1) -positive recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) in the KEYNOTE-012 trial. Results from the expansion cohort, in which patients with HNSCC, irrespective of biomarker status, received a fixed dose of pembrolizumab at a less frequent dosing schedule, are reported. Patients and Methods Patients with R/M HNSCC, irrespective of PD-L1 or human papillomavirus status, received pembrolizumab 200 mg intravenously once every 3 weeks. Imaging was performed every 8 weeks. Primary end points were overall response rate (ORR) per central imaging vendor (Response Evaluation Criteria in Solid Tumors v1.1) and safety. Secondary end points included progression-free survival, overall survival, and association of response and PD-L1 expression. Patients who received one or more doses of pembrolizumab were included in analyses. Results Of 132 patients enrolled, median age was 60 years (range, 25 to 84 years), 83% were male, and 57% received two or more lines of therapy for R/M disease. ORR was 18% (95% CI, 12 to 26) by central imaging vendor and 20% (95% CI, 13 to 28) by investigator review. Median duration of response was not reached (range, ≥ 2 to ≥ 11 months). Six-month progression-free survival and overall survival rates were 23% and 59%, respectively. By using tumor and immune cells, a statistically significant increase in ORR was observed for PD-L1-positive versus -negative patients (22% v 4%; P = .021). Treatment-related adverse events of any grade and grade ≥ 3 events occurred in 62% and 9% of patients, respectively. Conclusion Fixed-dose pembrolizumab 200 mg administered once every 3 weeks was well tolerated and yielded a clinically meaningful ORR with evidence of durable responses, which supports further development of this regimen in patients with advanced HNSCC

Impact of seasonal variation, age and smoking status on human semen parameters: The Massachusetts General Hospital experience

BACKGROUND: To investigate the relationship of human semen parameters with season, age and smoking status. METHODS: The present study used data from subjects recruited into an ongoing cross-sectional study on the relationship between environmental agents and semen characteristics. Our population consisted of 306 patients who presented to the Vincent Memorial Andrology Laboratory of Massachusetts General Hospital for semen evaluation. Sperm concentration and motility were measured with computer aided sperm analysis (CASA). Sperm morphology was scored using Tygerberg Kruger strict criteria. Regression analyses were used to investigate the relationships between semen parameters and season, age and smoking status, adjusting for abstinence interval. RESULTS: Sperm concentration in the spring was significantly higher than in winter, fall and summer (p < 0.05). There was suggestive evidence of higher sperm motility and percent of sperm with normal morphology in the spring than in the other seasons. There were no statistically significant relationships between semen parameters and smoking status, though current smokers tended to have lower sperm concentration. We also did not find a statistically significant relationship between age and semen parameters. CONCLUSIONS: We found seasonal variations in sperm concentration and suggestive evidence of seasonal variation in sperm motility and percent sperm with normal morphology. Although smoking status was not a significant predictor of semen parameters, this may have been due to the small number of current smokers in the study

Using the gut microbiota as a novel tool for examining colobine primate GI health

Primates of the Colobinae subfamily are highly folivorous. They possess a sacculated foregut and are believed to rely on a specialized gut microbiota to extract sufficient energy from their hard-to-digest diet. Although many colobines are endangered and would benefit from captive breeding programs, maintaining healthy captive populations of colobines can be difficult since they commonly suffer from morbidity and mortality due to gastrointestinal (GI) distress of unknown cause. While there is speculation that this GI distress may be associated with a dysbiosis of the gut microbiota, no study has directly examined the role of the gut microbiota in colobine GI health. In this study, we used high-throughput sequencing to examine the gut microbiota of three genera of colobines housed at the San Diego Zoo: doucs (Pygathrix) (N=7), colobus monkeys (Colobus) (N=4), and langurs (Trachypithecus) (N=5). Our data indicated that GI-healthy doucs, langurs, and colobus monkeys possess a distinct gut microbiota. In addition, GI-unhealthy doucs exhibited a different gut microbiota compared to GI-healthy individuals, including reduced relative abundances of anti-inflammatory Akkermansia. Finally, by comparing samples from wild and captive Asian colobines, we found that captive colobines generally exhibited higher relative abundances of potential pathogens such as Desulfovibrio and Methanobrevibacter compared to wild colobines, implying an increased risk of gut microbial dysbiosis. Together, these results suggest an association between the gut microbiota and GI illness of unknown cause in doucs. Further studies are necessary to corroborate these findings and determine cause-and-effect relationships. Additionally, we found minimal variation in the diversity and composition of the gut microbiota along the colobine GI tract, suggesting that fecal samples may be sufficient for describing the colobine gut microbiota. If these findings can be validated in wild individuals, it will facilitate the rapid expansion of colobine gut microbiome research

Indices of insulin sensitivity and secretion from a standard liquid meal test in subjects with type 2 diabetes, impaired or normal fasting glucose

<p>Abstract</p> <p>Background</p> <p>To provide an initial evaluation of insulin sensitivity and secretion indices derived from a standard liquid meal tolerance test protocol in subjects with normal (NFG), impaired fasting glucose (IFG) or type 2 diabetes mellitus.</p> <p>Methods</p> <p>Areas under the curve (AUC) for glucose, insulin and C-peptide from pre-meal to 120 min after consumption of a liquid meal were calculated, as were homeostasis model assessments of insulin resistance (HOMA2-IR) and the Matsuda index of insulin sensitivity.</p> <p>Results</p> <p>Subjects with NFG (n = 19), IFG (n = 19), and diabetes (n = 35) had mean ± SEM HOMA2-IR values of 1.0 ± 0.1, 1.6 ± 0.2 and 2.5 ± 0.3 and Matsuda insulin sensitivity index values of 15.6 ± 2.0, 8.8 ± 1.2 and 6.0 ± 0.6, respectively. The log-transformed values for these variables were highly correlated overall and within each fasting glucose category (r = -0.91 to -0.94, all p < 0.001). Values for the product of the insulin/glucose AUC ratio and the Matsuda index, an indicator of the ability of the pancreas to match insulin secretion to the degree of insulin resistance, were 995.6 ± 80.7 (NFG), 684.0 ± 57.3 (IFG) and 188.3 ± 16.1 (diabetes) and discriminated significantly between fasting glucose categories (p < 0.001 for each comparison).</p> <p>Conclusion</p> <p>These results provide initial evidence to support the usefulness of a standard liquid meal tolerance test for evaluation of insulin secretion and sensitivity in clinical and population studies.</p