GABA increases electrical excitability in a subset of human unmyelinated peripheral axons

A proportion of small diameter primary sensory neurones innervating human skin are chemosensitive. They respond in a receptor dependent manner to chemical mediators of inflammation as well as naturally occurring algogens, thermogens and pruritogens. The neurotransmitter GABA is interesting in this respect because in animal models of neuropathic pain GABA pre-synaptically regulates nociceptive input to the spinal cord. However, the effect of GABA on human peripheral unmyelinated axons has not been established

Management of allergic conjunctivitis: an evaluation of the perceived comfort and therapeutic efficacy of olopatadine 0.2% and azelastine 0.05% from two prospective studies

Arthur B Epstein1, Peter T Van Hoven2, Alan Kaufman3, Warner W Carr41North Shore Contact Lens and Vision Consultants, Roslyn Heights, NY, USA; 2Primary Eyecare Group PC, Brentwood, TN, USA; 3Adult Allergy Clinic and the Division of Allergy and Immunology, Our Lady of Mercy Medical Center, Bronx, NY, USA; 4Southern California Research, Mission Viejo, CA, USAPurpose: Results from 2 patient-reported outcome studies of allergic conjunctivitis sufferers who used olopatadine 0.2% and azelastine 0.05% are analyzed.Methods: The PACE (Pataday Allergic Conjunctivitis Evaluation) multi-center, prospective, open-label study examined patient perceptions of olopatadine 0.2% once daily (qd) and previous twice daily (bid) allergic conjunctivitis medications via questionnaire in allergic conjunctivitis sufferers who had previously used bid medication and then initiated olopatadine. A second conjunctival antigen challenge (CAC) study evaluated comfort of 4 allergic conjunctivitis medications. Results: Forty-nine patients from the PACE study (N = 125) with prior azelastine use were examined. Significantly more patients rated themselves “very satisfied” with current olopatadine use compared with past azelastine use on drop comfort (p < 0.0001), speed of relief (p = 0.0004), and overall satisfaction (70% vs 16%, p < 0.0001). Significantly more patients reported olopatadine “very effective” against swelling compared with azelastine (47% vs 8%, p = 0.0404). In the CAC study (N = 36), data from olopatadine (n = 8), azelastine (n = 9) and placebo (N = 36) groups were reported. Olopatadine was rated significantly more comfortable than azelastine upon instillation (p = 0.0223), at 30 seconds (p = 0.0479), and at 1 minute after instillation (p = 0.0240).Conclusion: In the reported studies, olopatadine 0.2% qd was more comfortable than azelastine 0.05% and preferred by patients with allergic conjunctivitis by a ratio of 4:1.Keywords: allergic conjunctivitis, azelastine, ocular allergy, olopatadine, patient perception

Isomerization dynamics of a buckled nanobeam

We analyze the dynamics of a model of a nanobeam under compression. The model is a two mode truncation of the Euler-Bernoulli beam equation subject to compressive stress. We consider parameter regimes where the first mode is unstable and the second mode can be either stable or unstable, and the remaining modes (neglected) are always stable. Material parameters used correspond to silicon. The two mode model Hamiltonian is the sum of a (diagonal) kinetic energy term and a potential energy term. The form of the potential energy function suggests an analogy with isomerisation reactions in chemistry. We therefore study the dynamics of the buckled beam using the conceptual framework established for the theory of isomerisation reactions. When the second mode is stable the potential energy surface has an index one saddle and when the second mode is unstable the potential energy surface has an index two saddle and two index one saddles. Symmetry of the system allows us to construct a phase space dividing surface between the two "isomers" (buckled states). The energy range is sufficiently wide that we can treat the effects of the index one and index two saddles in a unified fashion. We have computed reactive fluxes, mean gap times and reactant phase space volumes for three stress values at several different energies. In all cases the phase space volume swept out by isomerizing trajectories is considerably less than the reactant density of states, proving that the dynamics is highly nonergodic. The associated gap time distributions consist of one or more `pulses' of trajectories. Computation of the reactive flux correlation function shows no sign of a plateau region; rather, the flux exhibits oscillatory decay, indicating that, for the 2-mode model in the physical regime considered, a rate constant for isomerization does not exist.Comment: 42 pages, 6 figure

Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis.

BACKGROUND: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. METHODS: In a multinational retrospective cohort study, LA was defined as arterial blood pH5 mmol/l. Logistic regression was used to identify factors associated with fatality. Sensitivity and specificity of different case definitions as predictors of death were compared. RESULTS: The overall case-fatality rate was 19/110 (17.3%), but among acidotic patients it was 33% (16/49 cases). There were 10 asymptomatic patients and none of them died as a consequence of the event. The median lactate for fatal, non-fatal and all patients was 8.3 mmol/l (IQR 7.2-13.1), 6.4 mmol/l (IQR 5.4-7.8) and 6.7 mmol/l (IQR 5.5-8.1), respectively. After adjusting for age and current CD4(+) T-cell count, lactate >7 mmol/l (OR 6.27, 95% CI 1.13-34.93), blood bicarbonate 18 mmol/l, 95% CI 1.33-75.65) and concurrent opportunistic infections (OR 8.69, 95% CI 1.45-52.22) were independently associated with case fatality. Blood lactate >7 mmol/l showed a sensitivity of 84% for fatality with a specificity of 60%, whereas bicarbonate 7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring

Increased Trauma Activation Is Not Equally Beneficial For All Elderly Trauma Patients

Background Physiologic changes in the elderly lead to higher morbidity and mortality after injury. Increasing level of trauma activation has been proposed to improve geriatric outcomes; but, the increased cost to the patient and stress to the hospital system are significant downsides. The purpose of this study was to identify the age at which an increase in activation status is beneficial. Methods A retrospective review of trauma patients ≥ 70 years old from October 1, 2011, to October 1, 2016 was performed. On October 1, 2013, a policy change increased the activation criteria to the highest level for patients ≥ 70 years of age with a significant mechanism of injury. Patients who presented prior to (PRE) were compared to those after the change (POST). Data collected included age, injury severity score (ISS), length of stay (LOS), complications and mortality. Primary outcome was mortality and secondary outcome was LOS. Multivariable regressions controlled for age, ISS, injury mechanism, and number of complications. Results 4341 patients met inclusion criteria, 1919 in PRE and 2422 in POST. Mean age was 80.4 and 81 years in PRE and POST groups respectively (p=0.0155). Mean ISS values were 11.6 and 12.4 (p<0.0001) for the PRE and POST groups. POST had more level 1 activations (696 vs. 220, p<0.0001). After controlling for age, ISS, mechanism of injury, and number of complications, mortality was significantly reduced in the POST group ≥ age 77 years (OR 0.53, 95% CI: 0.3 - 0.87), (Figure 1). Hospital LOS was significantly reduced in the POST group ≥ age 78 (regression coefficient -0.55, 95% CI: -1.09, -0.01) (Figure 2). Conclusions This study suggests geriatric trauma patients ≥ 77 years benefit from the highest level of trauma activation with shorter LOS and lower mortality. A focused approach to increasing activation level for elderly patients may decrease patient cost. Level of Evidence Level III Type of Study Economic/Decisio

International cooperation for Mars exploration and sample return

The National Research Council's Space Studies Board has previously recommended that the next major phase of Mars exploration for the United States involve detailed in situ investigations of the surface of Mars and the return to earth for laboratory analysis of selected Martian surface samples. More recently, the European space science community has expressed general interest in the concept of cooperative Mars exploration and sample return. The USSR has now announced plans for a program of Mars exploration incorporating international cooperation. If the opportunity becomes available to participate in Mars exploration, interest is likely to emerge on the part of a number of other countries, such as Japan and Canada. The Space Studies Board's Committee on Cooperative Mars Exploration and Sample Return was asked by the National Aeronautics and Space Administration (NASA) to examine and report on the question of how Mars sample return missions might best be structured for effective implementation by NASA along with international partners. The committee examined alternatives ranging from scientific missions in which the United States would take a substantial lead, with international participation playing only an ancillary role, to missions in which international cooperation would be a basic part of the approach, with the international partners taking on comparably large mission responsibilities. On the basis of scientific strategies developed earlier by the Space Studies Board, the committee considered the scientific and technical basis of such collaboration and the most mutually beneficial arrangements for constructing successful cooperative missions, particularly with the USSR

A simple, robust orthogonal background correction method for two-dimensional liquid chromatography

Background correction is a very important step that must be performed before peak detection or any quantification procedure. When successful, this step greatly simplifies such procedures and enhances the accuracy of quantification. In the past, much effort has been invested to correct drifting baseline in one-dimensional chromatography. In fast online comprehensive two-dimensional liquid chromatography (LC×LC) coupled with a diode array detector (DAD), the change in the refractive index (RI) of the mobile phase in very fast gradients causes extremely serious baseline disturbances. The method reported here is based on the use of various existing baseline correction methods of one-dimensional (1D) liquid chromatography to correct the two-dimensional (2D) background in LC×LC. When such methods are applied orthogonally to the second dimension (2D), background correction is dramatically improved. The method gives an almost zero mean background level and it provides better background correction than does simple subtraction of a blank. Indeed, the method proposed does not require running a blank sample.Facultad de Ciencias Exacta

Ice front change of marine-terminating outlet glaciers in northwest and southeast Greenland during the 21st century

The increasingly negative mass balance of the Greenland ice sheet (GrIS) over the last ~25 years has been associated with enhanced surface melt and increased ice loss from marine-terminating outlet glaciers. Accelerated retreat during 2000–2010 was concentrated in the southeast and northwest sectors of the ice sheet; however, there was considerable spatial and temporal variability in the timing and magnitude of retreat both within and between these regions. This behaviour has yet to be quantified and compared for all glaciers in both regions. Furthermore, it is unclear whether retreat has continued after 2010 in the northwest, and whether the documented slowdown in the southeast post-2005 has been sustained. Here, we compare spatial and temporal patterns of frontal change in the northwest and southeast GrIS, for the period 2000–2015. Our results show near-ubiquitous retreat of outlet glaciers across both regions for the study period; however, the timing and magnitude of inter-annual frontal position change is largely asynchronous. We also find that since 2010, there is continued terminus retreat in the northwest, which contrasts with considerable inter-annual variability in the southeast. Analysis of the role of glacier-specific factors demonstrates that fjord and bed geometry are important controls on the timing and magnitude of glacier retreat

Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio