Where Have all the Patent Lawyers Gone? Long Time Passing...

This article pursues two distinct, but related hypotheses. First, as total LSAT takers decline, we expect to see a decline in the number of new attorneys admitted to the patent bar. Second, as the number of new patent attorneys shrinks and the number of women pursuing engineering degrees increases, we expect that the patent bar will become more female. In order to test these hypotheses, we gathered and collated data from the Law School Admission Counsel (LSAC) regarding students taking the Law School Admissions Test (LSAT), the United States Patent and Trademark Office (USPTO), the Society of Women Engineers (SWE), and the American Bar Association (ABA). The data establishes that the first hypothesis is true, but the second one is false. That is, the number of new entrants to the patent bar will drop precipitously. By 2018, new entrants will number one half of what they were in 2008. However, the number of female patent attorneys compared to the number of male patent attorneys will not change in this same time period. That is, even though the patent bar will shrink, the patent bar will not become more female

Where Have all the Patent Lawyers Gone? Long Time Passing...

This article pursues two distinct, but related hypotheses. First, as total LSAT takers decline, we expect to see a decline in the number of new attorneys admitted to the patent bar. Second, as the number of new patent attorneys shrinks and the number of women pursuing engineering degrees increases, we expect that the patent bar will become more female. In order to test these hypotheses, we gathered and collated data from the Law School Admission Counsel (LSAC) regarding students taking the Law School Admissions Test (LSAT), the United States Patent and Trademark Office (USPTO), the Society of Women Engineers (SWE), and the American Bar Association (ABA). The data establishes that the first hypothesis is true, but the second one is false. That is, the number of new entrants to the patent bar will drop precipitously. By 2018, new entrants will number one half of what they were in 2008. However, the number of female patent attorneys compared to the number of male patent attorneys will not change in this same time period. That is, even though the patent bar will shrink, the patent bar will not become more female

Anaemia in haemodialysis patients of five European countries: association with morbidity and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS)

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776-1 Selective Down-regulation of Angiotensin II AT1 Receptors in Failing Human Heart: Relationship to β1-Receptor Down-regulation

The renin-angiotensin and adrenergic nervous systems exhibit multiple levels of cross-regulation in heart failure. These systems are bidirectionally activated in concert; i.e. activation of one system activates the other. We compared the behavior of angiotensin II AT1 and AT2 receptors with β1, -and, β2-adrenergic receptors in a high-yield crude membrane fraction prepared from nonfailing and failing human ventricular myocardium. Ang II receptors were measured by 125I saralasin binding, with Bmax determined by saturation binding displaceable by 1μM cold saralasin. AT1 and AT2 receptor fractions were determined by the amount of specific binding displaceable by 1μM losartan. β1-adrenergic receptor density was determined by saturation binding of 125I ICYP, with the, β1 fraction determined by binding displaceable by 0.2μM CGP 20712A. Results in end-stage human left ventricular myocardium failing as a result of idiopathic dilated cardiomyopathy were compared to nonfailing controls taken from age- and gender-matched organ donors not used for transplant because of blood type or body size mismatch: (Receptor density is in fmol/mg±SEM)β1-ARβ2-ARAT1AT2Nonfailing (n=6)59.0±9.420.7±4.04.14±0.621.52±0.43Failing (n = 6)28.3±2.8*17.2±2.61.53±0.57*2.68±0.51*p<0.05The down-regulation of β1 AR and AT1 receptors was significantly related (r=0.62, n=12, p<0.05)Conclusions(1) Compared to β adrenergic receptors ang II receptors are very low density in the human heart. (2) The AT1 receptor sUbtype predominates in the nonfailing human heart. (3) ATl but not AT2 receptors are downregulated in failing heart. (4) Down-regulation of Ang-II AT1 receptor is similar in degree to down-regulation of β1-adrenergic receptors. These data suggest that the AT1 and β1 receptors are respectively exposed to increased concentrations of mutually activatedlinduced norepinephrine and Ang-II in the failing human heart

Investigations in vivo of the effects of carbogen breathing on 5-fluorouracil pharmacokinetics and physiology of solid rodent tumours

Purpose: We have shown previously that carbogen (95% 02, 5% CO2) breathing by rodents can increase uptake of anticancer drugs into tumours. The aim of this study was to extend these observations to other rodent models using the anticancer drug 5-fluorouracil (5FU). 5FU pharmacokinetics in tumour and plasma and physiological effects on the tumour by carbogen were investigated to determine the locus of carbogen action on augmenting tumour uptake of 5FU. Methods: Two different tumour models were used, rat GH3 prolactinomas xenografted s.c. into nude mice and rat H9618a hepatomas grown s.c. in syngeneic Buffalo rats. Uptake and metabolism of 5FU in both tumour models with or without host carbogen breathing was studied non-invasively using fluorine-19 magnetic resonance spectroscopy (19F-MRS), while plasma samples from Buffalo rats were used to construct a NONMEM pharmacokinetic model. Physiological effects of carbogen on tumours were studied using 31P-MRS for energy status (NTP/Pi) and pH, and gradient-recalled echo magnetic resonance imaging (GRE-MRI) for blood flow and oxygenation. Results: In both tumour models, carbogan-induced GRE-MRI signal intensity increases of ∼60% consistent with an increase in tumour blood oxygenation and/or flow. In GH3 xenografts, 19F-MRS showed that carbogen had no significant effect on 5FU uptake and metabolism by the tumours, and 31P-MRS showed there was no change in the NTP/Pi ratio. In H9618a hepatomas, 19F-MRS showed that carbogen had no effect on tumour 5FU uptake but significantly (p=0.0003) increased 5FU elimination from the tumour (i.e. decreased the t1/2) and significantly (p=0.029) increased (53%) the rate of metabolism to cytotoxic fluoronucleotides (FNuct). The pharmacokinetic analysis showed that carbogen increased the rate of tumour uptake of 5FU from the plasma but also increased the rate of removal. 31P-MRS showed there were significant (p≤0.02) increases in the hepatoma NTP/Pi ratio of 49% and transmembrane pH gradient of 0.11 units. Conclusions: We suggest that carbogen can transiently increase tumour blood flow, but this effect alone may not increase uptake of anticancer drugs without a secondary mechanism operating. In the case of the hepatoma, the increase in tumour energy status and pH gradient may be sufficient to augment 5FU metabolism to cytotoxic FNuct, while in the GH3 xenografts this was not the case. Thus carbogen breathing does not universally lead to increased uptake of anticancer drug

Evaluation of Neurocognition in Youth with CKD Using a Novel Computerized Neurocognitive Battery

BACKGROUND AND OBJECTIVES: Neurocognitive problems in CKD are well documented; time-efficient methods are needed to assess neurocognition in this population. We performed the first study of the efficient 1-hour Penn Computerized Neurocognitive Battery (CNB) in children and young adults with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We administered the Penn CNB cross-sectionally to individuals aged 8-25 years with stage 2-5 CKD (n=92, enrolled from three academic nephrology practices from 2011 to 2014) and matched healthy controls (n=69). We analyzed results from 12 tests in four domains: executive control, episodic memory, complex cognition, and social cognition. All tests measure accuracy and speed; we converted raw scores to age-specific z-scores on the basis of Philadelphia Neurodevelopmental Cohort (n=1790) norms. We analyzed each test in a linear regression with accuracy and speed z-scores as dependent variables and with (1) CKD versus control or (2) eGFR as explanatory variables, adjusted for race, sex, and maternal education. RESULTS: Patients with CKD (mean±SD eGFR, 48±25 ml/min per 1.73 m(2); mean age, 16.3±3.9 years) and controls (mean eGFR, 98±20 ml/min per 1.73 m(2); mean age, 16.0±4.0 years) were similar demographically. CKD participants had lower accuracy than controls in tests of complex cognition, with moderate to large effect sizes: -0.53 (95% confidence interval [95% CI], -0.87 to -0.19) for verbal reasoning, -0.52 (95% CI, -0.83 to -0.22) for nonverbal reasoning, and -0.64 (95% CI, -0.99 to -0.29) for spatial processing. For attention, patients with CKD had lower accuracy (effect size, -0.35 [95% CI, -0.67 to -0.03]) but faster response times (effect size, 0.44 [95% CI, 0.04 to 0.83]) than controls, perhaps reflecting greater impulsivity. Lower eGFR was associated with lower accuracy for complex cognition, facial and visual memory, and emotion identification tests. CONCLUSIONS: CKD is associated with lower accuracy in tests of complex cognition, attention, memory, and emotion identification, which related to eGFR. These findings are consistent with traditional neurocognitive testing in previous studies

Dimension of interaction dynamics

A method allowing to distinguish interacting from non-interacting systems based on available time series is proposed and investigated. Some facts concerning generalized Renyi dimensions that form the basis of our method are proved. We show that one can find the dimension of the part of the attractor of the system connected with interaction between its parts. We use our method to distinguish interacting from non-interacting systems on the examples of logistic and H\'enon maps. A classification of all possible interaction schemes is given.Comment: 15 pages, 14 (36) figures, submitted to PR

Obesity and the Risk of Papillary Thyroid Cancer: A Pooled Analysis of Three Case-Control Studies.

Background: There is a correlation between temporal trends of obesity prevalence and papillary thyroid cancer (PTC) incidence in the United States. Obesity is a well-recognized risk factor for many cancers, but there are few studies on the association between obesity and PTC risk. We investigated the association between anthropometric measurements and PTC risk using pooled individual data from three case–control populations. Methods: Height and weight information were obtained from three independent case–control studies, including 1917 patients with PTC (1360 women and 557 men) and 2127 cancer-free controls from the United States, Italy, and Germany. Body mass index (BMI), body fat percentage, and body surface area (BSA) were calculated. An unconditional logistic regression model was used to calculate odds ratios (ORs) and confidence intervals (CIs) with respect to risk of PTC, adjusted by age, sex, race/ethnicity, and study site. Results: In the pooled population, for both men and women, an increased risk of PTC was found to be associated with greater weight, BMI, body fat percentage, and BSA, whereas a reduced risk of PTC was associated with greater height, in the pooled population for both men and women. Compared with normal-weight subjects (BMI 18.5–24.9 kg/m2), the ORs for overweight (BMI 25–29.9 kg/m2) and obese (BMI ‡ 30 kg/m2) subjects were 1.72 [CI 1.48–2.00] and 4.17 [CI 3.41–5.10] respectively. Compared with the lowest quartile of body fat percentage, the ORs for the highest quartile were 3.83 [CI 2.85–5.15] in women and 4.05 [CI 2.67– 6.15] in men. Conclusion: Anthropometric factors, especially BMI and body fat percentage, were significantly associated with increased risk of PTC. Future studies of anthropometric factors and PTC that incorporate intermediate factors, including adiposity and hormone biomarkers, are essential to help clarify potential mechanisms of the relationship

Relative amounts of antagonistic splicing factors, hnRNP A1 and ASF/SF2, change during neoplastic lung growth: implications for pre-mRNA processing

Pre-mRNA processing is an important mechanism for globally modifying cellular protein composition during tumorigenesis. To understand this process during lung cancer, expression of two key pre-mRNA alternative splicing factors was compared in a mouse model of early lung carcinogenesis and during regenerative growth following reversible lung injury. Heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and alternative splicing factor/splicing factor 2 (ASF/SF2) act antagonistically to modulate splice site selection. Both hnRNP A1 and ASF/SF2 contents rose in adenomas and during injury-induced hyperplasia compared to control lungs, as measured by immunoblotting. While both proteins increased similarly during compensatory hyperplasia, hnRNP A1 increased to a much greater extent than ASF/SF2 in tumors, resulting in a 6-fold increase of the hnRNP A1 to ASF/SF2 ratio. Immunohistochemical analysis showed that hnRNP A1 localized exclusively within tumor nuclei, while ASF/SF2 appeared in cytoplasm and/or nuclei, depending on the growth pattern of the tumor cells. We also demonstrated cancer-associated changes in the pre-mRNA alternative splicing of CD44, a membrane glycoprotein involved in cell-cell and cell-extracellular matrix interactions. hnRNP A1 and ASF/SF2 expression is thus differentially altered in neoplastic lung cells by mechanisms that do not strictly arise from increased cell division. These changes are influenced by tumor histology and may be associated with production of variant CD44 mRNA isoforms