The contribution of the supplementary motor area to explicit and implicit timing: A high-definition transcranial Random Noise Stimulation (HD-tRNS) study.

It is becoming increasingly accepted that timing tasks, and underlying temporal processes, can be partitioned on the basis of whether they require an explicit or implicit temporal judgement. Most neuroimaging studies of timing associated explicit timing tasks with activation of the supplementary motor area (SMA). However, transcranial magnetic stimulation (TMS) studies perturbing SMA functioning across explicit timing tasks have generally reported null effects, thus failing to causally link SMA to explicit timing. The present study probed the involvement of SMA in both explicit and implicit timing tasks within a single experiment and using High-Definition transcranial Random Noise Stimulation (HD-tRNS), a previously less used technique in studies of the SMA. Participants performed two tasks that comprised the same stimulus presentation but differed in the received task instructions, which might or might not require explicit temporal judgments. Results showed a significant HD-tRNS-induced shift of perceived durations (i.e., overestimation) in the explicit timing task, whereas there was no modulation of implicit timing by HD-tRNS. Overall, these results provide initial non-invasive brain stimulation evidence on the contribution of the SMA to explicit and implicit timing tasks.

Time series analysis of water use and indirect reuse within a HUC-4 basin (Wabash) over a nine year period.

Anthropogenic water use and reuse represent major components of the water cycle. In the context of climate change, water reuse and recycling are considered necessary components for an integrated water management approach. Unplanned, or de facto, indirect water reuse occurs in most of the U.S. river systems, however, there is little real-time documentation of it. Despite the fact that there are national and state agencies that systematically collect data on water withdrawals and wastewater discharges, their databases are organized and managed in a way that makes it challenging to use them for water resource management analysis. The ability to combine reported water data to perform large scale analysis about water use and reuse is severely limited. In this paper, we apply a simple but effective methodology to complete a time series watershed-scale analysis of water use and unplanned indirect reuse for the Wabash River Watershed. Results document the occurrence of indirect water reuse, ranging from 3% to 134%, in a water-rich area of the U.S. The time series analysis shows that reported data effectively describe the water use trends through nine years, from 2009 to 2017, clearly reflecting both anthropogenic and natural events in the watershed, such as the retirement of thermoelectric power plants, and the occurrence of an extreme drought in 2012. We demonstrate the feasibility and significance of using available water datasets to perform large scale water use analysis, describe limitations encountered in the process, and highlight areas for improvement in water data management.

Functional and radioligand binding characterization of the α1L-adrenoceptor subtype of the human vas deferens.

Alpha1 -adrenoceptor antagonists can cause ejaculatory dysfunction as an adverse effect. Contractions of the human vas deferens are mediated via α1A -adrenoceptors, and this study investigated whether the low affinity state of this receptor (α1L -adrenoceptor) is involved in mediating contractions of this tissue. The potency of agonists and the affinity of receptor subtype selective antagonists were determined in functional experiments and in [(3) H]tamsulosin binding experiments to identify the α1 -adrenoceptor subtype population present in the human vas deferens. The α1A -adrenoceptor selective agonist A61603 was a full agonist and was 250-fold more potent than noradrenaline. Prazosin antagonized contractile responses to phenylephrine with a low affinity (pKd = 8.6). Only high concentrations of RS17053 antagonized responses to phenylephrine and yielded a relatively low affinity estimate of 7.0. BMY7378 (α1D -adrenoceptor selective) gave a low affinity estimate (pKd = 6.7), whilst tamsulosin (α1A - and α1D -adrenoceptor selective) had a high affinity (pKd = 9.9). [(3) H]Tamsulosin bound to human vas deferens membranes with a high affinity (pKd = 10.0). Prazosin, RS17053 and BMY7378 competed with [(3) H]tamsulosin with low affinities for a single population of binding sites (pKd values of 8.5, 7.2 and 6.3, respectively). These functional and radioligand binding data indicate that the human vas deferens possesses a homogeneous population of α1 -adrenoceptors which have the pharmacological properties of the putative α1L -adrenoceptor, the same functional receptor previously identified in the human prostate.

Unmet dental and orthodontic need of children with special healthcare needs in West Virginia.

INTRODUCTION: Of children aged 0-17 years in the USA, an estimated 11 203 616 (15.1%; 95% CI: 14.8, 15.3) are Children with Special Health Care Needs (CSHCN). The state of West Virginia, the heart of Appalachia, has a land mass which is 97.65% rural with previously identified high overall dental need and oral health disparities. It is home to an estimated 70 609 CSHCN, or 18.5% (95% CI: 17.0, 19.9) of the state's children in 2009-2010. The purpose of this study was to determine the parent/guardian's perceived unmet dental care need of CSHCN in West Virginia. METHODS: Data from the National Survey of Children with Special Health Care Needs was used to determine prevalence. A telephone survey of 59 941 parents/guardians of CSHCN (1149 from West Virginia) for the dental interview was conducted in 2009-2010. RESULTS: Nationwide, 26.7% (25.9, 27.5) of parents/guardians reported their CSHCN had dental care or orthodontia needs other than preventive care. In West Virginia, the perceived dental care or orthodontia needs other than preventive dental care need was 26.5% (22.2, 30.0). Unmet national dental care need other than preventive dental care was 5.4% (5.0, 5.9) and in West Virginia 5.0% (2.4, 7.5). CONCLUSIONS: CSHCN have significant unmet dental needs. Parents/guardians in West Virginia reported similar unmet need compared with national reporting. Policies to address the health care of CSHCN should include dental needs. The clinical implications are that CSHCN have a variety of needs, including orthodontia. The benefits of orthodontic referrals should be considered in treatment planning options for CSHCN.

Breastfeeding prevalence and distribution in the USA and Appalachia by rural and urban setting.

INTRODUCTION: Breastfeeding provides health benefits to infants and mothers, yet many women decide against breastfeeding. This study examined differences in the prevalence of breastfeeding among national, urban, rural, and Appalachian regions of the USA. METHODS: Secondary data analysis of the US 2007 National Survey of Children's Health (n=27 388) data were completed for prevalence, insurance coverage, and medical home (a source of comprehensive primary care) determinations according to rural or urban location. RESULTS: The weighted US and Appalachian prevalences of breastfeeding were 0.755 (CI 0.743-0.767) and 0.683 (CI 0.672-0.694). National and Appalachian urban prevalences were 0.770 (CI 0.757-0.784) and 0.715 (CI 0.702-0.728). Rural areas had a significantly lower prevalence of breastfeeding of 0.687 (CI 0.661-0.713). Appalachia was significantly lower than the national rural level at 0.576 (CI 0.554-0.598). Women with Medicaid/State Children's Health Insurance Program (SCHIP) had an odds ratio of 1.79 of not breastfeeding compared with privately insured women. Nationally, 26.6% (CI 24.5-28.7) of children of women who did not breastfeed did not have a medical home. CONCLUSIONS: Anticipatory guidance about breastfeeding with culturally sensitive awareness programs and interventions directed at rural populations, especially in high risk geographic areas such as Appalachia, may be needed. Healthcare professionals have a unique opportunity to provide anticipatory guidance to pregnant women by discussing the benefits of breastfeeding during visits. High school health educational programs should address the benefits of breastfeeding with rural females.

Follow-up schedules after treatment for malignant melanoma.

BACKGROUND: Existing follow-up guidelines after treatment for melanoma are based largely on dated literature and historical precedent. This study aimed to calculate recurrence rates and establish prognostic factors for recurrence to help redesign a follow-up schedule. METHODS: Data were retrieved from the Sydney Melanoma Unit database for all patients with a single primary melanoma and American Joint Committee on Cancer (AJCC) stage I-II disease, who had received their first treatment between 1959 and 2002. Recurrence rates, timing and survival were recorded by substage, and predictive factors were analysed. RESULTS: Recurrence occurred in 18.9 per cent (895 of 4748) of patients overall, 5.2 per cent (95 of 1822) of those with stage IA disease, 18.4 per cent (264 of 1436) with IB, 28.7 per cent (215 of 750) with IIA, 40.6 per cent (213 of 524) with IIB and 44.3 per cent (86 of 194) with IIC disease. Overall, the median disease-free survival time was 2.6 years, but there were marked differences between AJCC subgroups. Primary tumour thickness, ulceration and tumour mitotic rate were important predictors of recurrence. CONCLUSION: A new follow-up schedule was proposed: stage I annually, stage IIA 6-monthly for 2 years and then annually, stage IIB-IIC 4-monthly for 2 years, 6-monthly in the third year and annually thereafter.

Abnormal thyroid function in older men with or at risk for HIV infection.

OBJECTIVES: The aim of the study was to evaluate the prevalence of and factors associated with abnormal thyroid function in older men with or at risk for HIV infection. METHODS: A cross-sectional analysis of 636 men > or =49 years old was carried out using data obtained from interviews, from measurements of body mass index (BMI), HIV-1 serology and viral load, CD4 cell count, hepatitis C virus (HCV) assays, thyroid-stimulating hormone (TSH) and free thyroid hormone levels. RESULTS: Participants were 54% black, 57% overweight/obese, 57% HIV seropositive, and 72% HCV seropositive; 38% reported recent cocaine or heroin use. Decreased TSH was found in 56 men (8.8%) and raised TSH in 23 men (3.6%). Only three men had abnormal free thyroxine levels. CONCLUSIONS: Abnormal TSH levels were noted in 12.4% of older men with or at risk for HIV infection, but nearly all reflected subclinical hyperthyroidism or subclinical hypothyroidism.

Lactic acidosis after treatment with linezolid.

Linezolid is currently indicated to treat vancomycin-resistant Enterococcus faecium infections, nosocomial pneumonia caused by Staphylococcus aureus or Streptococcus pneumoniae, complicated and uncomplicated skin and skin structure infections, and community-acquired pneumonia. We report a case of linezolid-induced lactic acidosis during treatment of vancomycin-resistant enterococcal bacteremia after mitral valve replacement and permanent pacemaker implantation. We also review the current literature describing other cases of linezolid-associated hyperlactatemia.

Rapid right ventricular pacing is an alternative to adenosine in catheter interventional procedures for congenital heart disease.

OBJECTIVE: To describe the use of rapid right ventricular pacing to facilitate balloon stability during balloon dilatation procedures for congenital heart disease. SETTING: Tertiary paediatric cardiac centre. DESIGN AND PATIENTS: This was a prospective pilot study of 37 consecutive patients with congenital aortic stenosis undergoing elective balloon dilatation. If the first dilatation manoeuvre failed due to balloon displacement, rapid right ventricular pacing at a rate of 220 beats/min was performed during repeat balloon inflation. INTERVENTIONS: Balloon aortic valvotomy and rapid right ventricular pacing. MAIN OUTCOME MEASURES: Balloon stability versus displacement during balloon dilatation and procedure related complications. RESULTS: Initial balloon displacement occurred and rapid right ventricular pacing was performed in 14 patients. The balloon remained in stable position in 11 patients. In three patients the balloon was displaced. In two of them an increase of the pacing rate to 240 beats/min provided balloon stability. In one patient stability was obtained at an unchanged pacing rate after correction of a suboptimal balloon position. No sustained arrhythmias occurred. There were no other procedure related complications. CONCLUSIONS: Rapid right ventricular pacing is a safe and effective method to provide balloon stability during balloon dilatation of the aortic valve. It may be applied in other fields of catheter intervention where it is desirable to maintain stable device positions during the critical phase of the procedure.

Consistency of encoding in monkey visual cortex.

Are different kinds of stimuli (for example, different classes of geometric images or naturalistic images) encoded differently by visual cortex, or are the principles of encoding the same for all stimuli? We examine two response properties: (1) the range of spike counts that can be elicited from a neuron in epochs representative of short periods of fixation (up to 400 msec), and (2) the relation between mean and variance of spike counts elicited by different stimuli, that together characterize the information processing capabilities of a neuron using the spike count code. In monkey primary visual cortex (V1) complex cells, we examine responses elicited by static stimuli of four kinds (photographic images, bars, gratings, and Walsh patterns); in area TE of inferior temporal cortex, we examine responses elicited by static stimuli in the sample, nonmatch, and match phases of a delayed match-to-sample task. In each area, the ranges of mean spike counts and the relation between mean and variance of spike counts elicited are sufficiently similar across experimental conditions that information transmission is unaffected by the differences across stimulus set or behavioral conditions [although in 10 of 27 (37%) of the V1 neurons there are statistically significant but small differences, the median difference in transmitted information for these neurons was 0.9%]. Encoding therefore appears to be consistent across experimental conditions for neurons in both V1 and TE, and downstream neurons could decode all incoming signals using a single set of rules.

Thromboagglutination by anticardiolipin antibody complex in the antiphospholipid syndrome: a possible mechanism of immune-mediated thrombosis.

The tendency for patients with antiphospholipid syndrome (APLS) to thromboembolism and the criteria for its detection are well established, whereas the mechanism of this thrombophilic syndrome is still obscure. Using immunofluorescent techniques and a microscopic spontaneous platelet aggregation test (mSPAT), we have previously demonstrated platelet binding by antibody followed by aggregation in patients with lupus anticoagulant. In the present study, we investigated 18 anticardiolipin antibody-positive (ACLA pos.) patients, comprised of 12 primary APLS and 6 secondary APLS lupus patients. We demonstrated direct platelet microaggregate formation in 16/18 cases, whereas this finding was not present in 20 ACLA-negative (ACLA neg.) subjects (P<.001). Indirect testing revealed 10/12 cases of platelet microaggregation and none in the ACLA neg. subjects. In addition, immunofluorescent studies showed that platelet antibody complex binding occurred in 8/12 cases tested directly and in 11/12 cases in indirect testing, as compared to 1 out of 20 binding in ACLA neg. subjects (P<.001). Antibody complex binding was inhibited in two cases by prior extraction of phospholipids. Platelet aggregation could be demonstrated in two ACLA neg. individuals by the addition of exogenous ACLA to platelets in EDTA-plasma. We therefore propose a mechanism for immune-mediated thrombosis in APLS in which calcium-independent platelet aggregation, or thromboagglutination, is initiated by an ACLA-phospholipid complex present in the patients' plasma. Following the antibody complex-induced platelet agglutination, thrombosis proceeds by release, recruitment, and fibrin formation. The mechanism should have important implications in the diagnosis, management, and monitoring of APLS.

Geometric visual hallucinations, Euclidean symmetry and the functional architecture of striate cortex.

This paper is concerned with a striking visual experience: that of seeing geometric visual hallucinations. Hallucinatory images were classified by Klüver into four groups called form constants comprising (i) gratings, lattices, fretworks, filigrees, honeycombs and chequer-boards, (ii) cobwebs, (iii) tunnels, funnels, alleys, cones and vessels, and (iv) spirals. This paper describes a mathematical investigation of their origin based on the assumption that the patterns of connection between retina and striate cortex (henceforth referred to as V1)-the retinocortical map-and of neuronal circuits in V1, both local and lateral, determine their geometry. In the first part of the paper we show that form constants, when viewed in V1 coordinates, essentially correspond to combinations of plane waves, the wavelengths of which are integral multiples of the width of a human Hubel-Wiesel hypercolumn, ca. 1.33-2 mm. We next introduce a mathematical description of the large-scale dynamics of V1 in terms of the continuum limit of a lattice of interconnected hypercolumns, each of which itself comprises a number of interconnected iso-orientation columns. We then show that the patterns of interconnection in V1 exhibit a very interesting symmetry, i.e. they are invariant under the action of the planar Euclidean group E(2)-the group of rigid motions in the plane-rotations, reflections and translations. What is novel is that the lateral connectivity of V1 is such that a new group action is needed to represent its properties: by virtue of its anisotropy it is invariant with respect to certain shifts and twists of the plane. It is this shift-twist invariance that generates new representations of E(2). Assuming that the strength of lateral connections is weak compared with that of local connections, we next calculate the eigenvalues and eigenfunctions of the cortical dynamics, using Rayleigh-Schrödinger perturbation theory. The result is that in the absence of lateral connections, the eigenfunctions are degenerate, comprising both even and odd combinations of sinusoids in straight phi, the cortical label for orientation preference, and plane waves in r, the cortical position coordinate. 'Switching-on' the lateral interactions breaks the degeneracy and either even or else odd eigenfunctions are selected. These results can be shown to follow directly from the Euclidean symmetry we have imposed. In the second part of the paper we study the nature of various even and odd combinations of eigenfunctions or planforms, the symmetries of which are such that they remain invariant under the particular action of E(2) we have imposed. These symmetries correspond to certain subgroups of E(2), the so-called axial subgroups. Axial subgroups are important in that the equivariant branching lemma indicates that when a symmetrical dynamical system becomes unstable, new solutions emerge which have symmetries corresponding to the axial subgroups of the underlying symmetry group. This is precisely the case studied in this paper. Thus we study the various planforms that emerge when our model V1 dynamics become unstable under the presumed action of hallucinogens or flickering lights. We show that the planforms correspond to the axial subgroups of E(2), under the shift-twist action. We then compute what such planforms would look like in the visual field, given an extension of the retinocortical map to include its action on local edges and contours. What is most interesting is that, given our interpretation of the correspondence between V1 planforms and perceived patterns, the set of planforms generates representatives of all the form constants. It is also noteworthy that the planforms derived from our continuum model naturally divide V1 into what are called linear regions, in which the pattern has a near constant orientation, reminiscent of the iso-orientation patches constructed via optical imaging. The boundaries of such regions form fractures whose points of intersection correspond to the well-known 'pinwheels'. To complete the study we then investigate the stability of the planforms, using methods of nonlinear stability analysis, including Liapunov-Schmidt reduction and Poincaré-Lindstedt perturbation theory. We find a close correspondence between stable planforms and form constants. The results are sensitive to the detailed specification of the lateral connectivity and suggest an interesting possibility, that the cortical mechanisms by which geometric visual hallucinations are generated, if sited mainly in V1, are closely related to those involved in the processing of edges and contours.

Estimates of the health risk reductions associated with attainment of alternative particulate matter standards in two U.S. cities.

As part of its periodic re-evaluation of particulate matter (PM) standards, the U.S. Environmental Protection Agency estimated the health risk reductions associated with attainment of alternative PM standards in two locations in the United States with relatively complete air quality data: Philadelphia and Los Angeles. PM standards at the time of the analysis were defined for particles of aerodynamic diameter less than or equal to 10 microm, denoted as PM-10. The risk analyses estimated the risk reductions that would be associated with changing from attainment of the PM-10 standards then in place to attainment of alternative standards using an indicator measuring fine particles, defined as those particles of aerodynamic diameter less than or equal to 2.5 microm and denoted as PM-2.5. Annual average PM-2.5 standards of 12.5, 15, and 20 microg/m3 were considered in various combinations with daily PM-2.5 standards of 50 and 65 microg/m3. Attainment of a standard or set of standards was simulated by a proportional rollback of "as is" daily PM concentrations to daily PM concentrations that would just meet the standard(s). The predicted reductions in the incidence of health effects varied from zero, for those alternative standards already being met, to substantial reductions of over 88% of all PM-associated incidence (e.g., in mortality associated with long-term exposures in Los Angeles, under attainment of an annual standard of 12.5 microg/m3). Sensitivity analyses and integrated uncertainty analyses assessed the multiple-source uncertainty surrounding estimates of risk reduction.

Bacterial export takes its Tol.

The recent crystal structure of TolC elegantly indicates its function and provides insight into its mechanism for export of a wide range of molecules across the periplasmic space and outer membrane of Gram-negative bacteria. The structure is compared to those of other proteins that are embedded in bacterial outer membranes or that traverse the periplasmic space.

Mesoscopic surfactant organization and membrane protein crystallization.

The paucity of detailed X-ray crystallographic structures of integral membrane proteins arises from substantive technical obstacles in the overexpression of multimilligram quantities of protein, and in the crystallization of purified protein-detergent complexes (PDCs). With rare exception, crystal contacts within the lattice are mediated by protein-protein interaction, and the detergent surrounding the protein behaves as a disordered solvent. The addition and use of surfactants that display mesoscopic self-assembly behavior in membrane protein crystallization experiments presents a novel alternative strategy. Well-ordered crystals of the water channel human aquaporin-1 (hAQP1) that diffract to 4 A resolution have been obtained with this approach.

The effect of full protective gear on intubation performance by hospital medical personnel.

OBJECTIVE: To assess the influence of protective gear on intubation performance. DESIGN: Prospective, controlled measurement of duration and quality of intubations performed on mannequins by medical personnel with and without protective gear in a crossover design. PARTICIPANTS: Eight teams each comprising an anesthesiologist and a nurse. RESULTS: Intubation duration with and without chemical warfare gear was 69.2 +/- 7 and 47.3 +/- 6 seconds (mean +/- SEM), respectively (p < 0.05). Moreover, rating of intubation quality as "very good" by the anesthesiologists declined significantly from 62.5% without chemical warfare protective gear to 6.25% with the garment and mask. Tube fixation was the rate-limiting step when performed with protective gear (p < 0.05); it was assessed by 81% of the anesthesiologists as the critical step. A learning curve was not observed during the study. CONCLUSION: Protective gear causes a significant prolongation of intubation duration; however, endotracheal intubation can be performed effectively. Technical improvements are warranted for tube fixation because it is the critical step.