Acute Effects of Acetazoleamide (Diamox) Administration on Pulmonary Carbon Dioxide Exchange in Humans

Previous studies dealing with the effects of oral acetazoleamide (DiamoxR) administration in humans have yielded equivocal results. Effects of intravenous administration of this agent, a potent carbonic anhydrase inhibitor, have not been studied until recently. It is postulated that difficulty in interpreting these results has risen in part from failure to evaluate given parameters in terms of drug concentrations or degree of carbonic anhydrase inhibition achieved. These concentrations were ascertained throughout the present work of this Thesis, which deals with the effects of both small and large doses of this agent upon ventilatory parameters in man. In these studies, normal fasting young males were first studied after an oral dose of 10 mg/kg using standard techniques of spirometry and gas analysis. No differences in minute volume, end-tidal (alveolar) pCO\u3e2/ or other ventilatory parameters were observed one hour after the drug was administered, while breathing room air or 10% oxygen at rest. However, an increased ventilatory response to 2 and 4% carbon dioxide in air was observed after oral administration of this dose. After a sufficiently large (35-50 mg/kg) intravenous dose, a concentration-related decrease in the alveolararterial (A/a) pC02 ratio similar to that earlier observed in dogs was observed. Blood gas determinations were carried out using suitable electrodes. The A/a pCO2 ratios after this dosage were between 0.8-0.6 at rest (normal*!.0) and dropped to 0.3 during exercise. This decrease was effected at a red cell concentration of from 60-80 micrograms/ ml, considerably greater than that necessary to achieve similar results in dogs. This decrease in A/a pCO2 ratio was associated with a transient hyperpnea and a fall in respiratory quotient secondary to a decrease in carbon dioxide output. These data are interpreted as indicating a definite. dose-related effect of acetazoleamide upon carbon dioxide output and ventilation in humans. The acute effects of the drug occur prior to the renal diuresis of bicarbonate, and are consistent with the development of an impediment to carbon dioxide transport across the alveolar-capillary junction in the lung. These effects are maximal when the transport time of the blood through the lung is shortened and the metabolic production of carbon dioxide is increased, as is the case during exercise. In this case, the speed of the alternate carriage mechanisms (primarily carbaminobound carbon dioxide) are probably not adequate to handle the increased demands placed upon the carriage system. These studies indicate that at dosage levels which can be tolerated by humans the drug probably has no use in producing a rapid, artificial acclimatization to high altitude. Recent in vitro studies have indicated quantitative differences between canine and human erythrocytic carbonic anhydrase. These differences probably account for the discrepancies which have existed in data obtained from such subjects

Multi-dimensional microwave sensing using graphene waveguides

This paper presents an electrolytically gated broadband microwave sensor where atomically-thin graphene layers are integrated into coplanar waveguides and coupled with microfluidic channels. The interaction between a solution under test and the graphene surface causes material and concentration-specific modifications of graphene's DC and AC conductivity. Moreover, wave propagation in the waveguide is modified by the dielectric properties of materials in its close proximity via the fringe field, resulting in a combined sensing mechanism leading to an enhanced S-parameter response compared to metallic microwave sensors. The possibility of further controlling the graphene conductivity via an electrolytic gate enables a new, multi-dimensional approach merging chemical field-effect sensing and microwave measurement methods. By controlling and synchronizing frequency sweeps, electrochemical gating and liquid flow in the microfluidic channel, we generate multidimensional datasets that enable a thorough investigation of the solution under study. As proof of concept, we functionalize the graphene surface in order to identify specific single-stranded DNA sequences dispersed in phosphate buffered saline solution. We achieve a limit of detection of ~1 attomole per litre for a perfect match DNA strand and a sensitivity of ~3 dB/decade for sub-pM concentrations. These results show that our devices represent a new and accurate metrological tool for chemical and biological sensing

Error Rates, Decisive Outcomes and Publication Bias with Several Inferential Methods

Correction to this article published Hopkins, W.G. & Batterham, A.M. Sports Med (2016) 46: 923. doi:10.1007/s40279-016-0530-

Elevated carbon dioxide and ozone alter productivity and ecosystem carbon content in northern temperate forests

Three young northern temperate forest communities in the north‐central United States were exposed to factorial combinations of elevated carbon dioxide ( CO 2 ) and tropospheric ozone (O 3 ) for 11 years. Here, we report results from an extensive sampling of plant biomass and soil conducted at the conclusion of the experiment that enabled us to estimate ecosystem carbon (C) content and cumulative net primary productivity ( NPP ). Elevated CO 2 enhanced ecosystem C content by 11%, whereas elevated O 3 decreased ecosystem C content by 9%. There was little variation in treatment effects on C content across communities and no meaningful interactions between CO 2 and O 3 . Treatment effects on ecosystem C content resulted primarily from changes in the near‐surface mineral soil and tree C, particularly differences in woody tissues. Excluding the mineral soil, cumulative NPP was a strong predictor of ecosystem C content ( r 2  = 0.96). Elevated CO 2 enhanced cumulative NPP by 39%, a consequence of a 28% increase in canopy nitrogen (N) content (g N m −2 ) and a 28% increase in N productivity ( NPP /canopy N). In contrast, elevated O 3 lowered NPP by 10% because of a 21% decrease in canopy N, but did not impact N productivity. Consequently, as the marginal impact of canopy N on NPP (∆ NPP /∆N) decreased through time with further canopy development, the O 3 effect on NPP dissipated. Within the mineral soil, there was less C in the top 0.1 m of soil under elevated O 3 and less soil C from 0.1 to 0.2 m in depth under elevated CO 2 . Overall, these results suggest that elevated CO 2 may create a sustained increase in NPP , whereas the long‐term effect of elevated O 3 on NPP will be smaller than expected. However, changes in soil C are not well‐understood and limit our ability to predict changes in ecosystem C content.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/108065/1/gcb12564.pd

Elevated carbon dioxide and ozone alter productivity and ecosystem carbon content in northern temperate forests

Three young northern temperate forest communities in the north-central United States were exposed to factorial combinations of elevated carbon dioxide (CO2) and tropospheric ozone (O3) for 11 years. Here, we report results from an extensive sampling of plant biomass and soil conducted at the conclusion of the experiment that enabled us to estimate ecosystem carbon (C) content and cumulative net primary productivity (NPP). Elevated CO2 enhanced ecosystem C content by 11%, whereas elevated O3 decreased ecosystem C content by 9%. There was little variation in treatment effects on C content across communities and no meaningful interactions between CO2 and O3. Treatment effects on ecosystem C content resulted primarily from changes in the near-surface mineral soil and tree C, particularly differences in woody tissues. Excluding the mineral soil, cumulative NPP was a strong predictor of ecosystem C content (r2 = 0.96). Elevated CO2 enhanced cumulative NPP by 39%, a consequence of a 28% increase in canopy nitrogen (N) content (g N m−2) and a 28% increase in N productivity (NPP/canopy N). In contrast, elevated O3 lowered NPP by 10% because of a 21% decrease in canopy N, but did not impact N productivity. Consequently, as the marginal impact of canopy N on NPP (ΔNPP/ΔN) decreased through time with further canopy development, the O3 effect on NPP dissipated. Within the mineral soil, there was less C in the top 0.1 m of soil under elevated O3 and less soil C from 0.1 to 0.2 m in depth under elevated CO2. Overall, these results suggest that elevated CO2 may create a sustained increase in NPP, whereas the long-term effect of elevated O3 on NPP will be smaller than expected. However, changes in soil C are not well-understood and limit our ability to predict changes in ecosystem C content

A theoretical and empirical investigation of nutritional label use

Due in part to increasing diet-related health problems caused, among others, by obesity, nutritional labelling has been considered important, mainly because it can provide consumers with information that can be used to make informed and healthier food choices. Several studies have focused on the empirical perspective of nutritional label use. None of these studies, however, have focused on developing a theoretical economic model that would adequately describe nutritional label use based on a utility theoretic framework. We attempt to fill this void by developing a simple theoretical model of nutritional label use, incorporating the time a consumer spends reading labels as part of the food choice process. The demand equations of the model are then empirically tested. Results suggest the significant role of several variables that flow directly from the model which, to our knowledge, have not been used in any previous empirical work

New generalized fuzzy metrics and fixed point theorem in fuzzy metric space

In this paper, in fuzzy metric spaces (in the sense of Kramosil and Michalek (Kibernetika 11:336-344, 1957)) we introduce the concept of a generalized fuzzy metric which is the extension of a fuzzy metric. First, inspired by the ideas of Grabiec (Fuzzy Sets Syst. 125:385-389, 1989), we define a new G-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by M Grabiec). Next, inspired by the ideas of Gregori and Sapena (Fuzzy Sets Syst. 125:245-252, 2002), we define a new GV-contraction of Banach type with respect to this generalized fuzzy metric, which is a generalization of the contraction of Banach type (introduced by V Gregori and A Sapena). Moreover, we provide the condition guaranteeing the existence of a fixed point for these single-valued contractions. Next, we show that the generalized pseudodistance J:X×X→[0,∞) (introduced by Włodarczyk and Plebaniak (Appl. Math. Lett. 24:325-328, 2011)) may generate some generalized fuzzy metric NJ on X. The paper includes also the comparison of our results with those existing in the literature

Prospects for progress on health inequalities in England in the post-primary care trust era : professional views on challenges, risks and opportunities

Background - Addressing health inequalities remains a prominent policy objective of the current UK government, but current NHS reforms involve a significant shift in roles and responsibilities. Clinicians are now placed at the heart of healthcare commissioning through which significant inequalities in access, uptake and impact of healthcare services must be addressed. Questions arise as to whether these new arrangements will help or hinder progress on health inequalities. This paper explores the perspectives of experienced healthcare professionals working within the commissioning arena; many of whom are likely to remain key actors in this unfolding scenario. Methods - Semi-structured interviews were conducted with 42 professionals involved with health and social care commissioning at national and local levels. These included representatives from the Department of Health, Primary Care Trusts, Strategic Health Authorities, Local Authorities, and third sector organisations. Results - In general, respondents lamented the lack of progress on health inequalities during the PCT commissioning era, where strong policy had not resulted in measurable improvements. However, there was concern that GP-led commissioning will fare little better, particularly in a time of reduced spending. Specific concerns centred on: reduced commitment to a health inequalities agenda; inadequate skills and loss of expertise; and weakened partnership working and engagement. There were more mixed opinions as to whether GP commissioners would be better able than their predecessors to challenge large provider trusts and shift spend towards prevention and early intervention, and whether GPs’ clinical experience would support commissioning action on inequalities. Though largely pessimistic, respondents highlighted some opportunities, including the potential for greater accountability of healthcare commissioners to the public and more influential needs assessments via emergent Health & Wellbeing Boards. Conclusions - There is doubt about the ability of GP commissioners to take clearer action on health inequalities than PCTs have historically achieved. Key actors expect the contribution from commissioning to address health inequalities to become even more piecemeal in the new arrangements, as it will be dependent upon the interest and agency of particular individuals within the new commissioning groups to engage and influence a wider range of stakeholders.</p