The Autonomous Mind: The Right to Freedom of Thought in the Twenty-First Century.
To lose freedom of thought (FoT) is to lose our dignity, our democracy and our very selves. Accordingly, the right to FoT receives absolute protection under international human rights law. However, this foundational right has been neither significantly developed nor often utilized. The contours of this right urgently need to be defined due to twenty-first century threats to FoT posed by new technologies. As such, this paper draws on law and psychology to consider what the right to FoT should be in the twenty-first century. After discussing contemporary threats to FoT, and recent developments in our understanding of thought that can inform the development of the right, this paper considers three elements of the right; the rights not to reveal one's thoughts, not to be penalized for one's thoughts, and not to have one's thoughts manipulated. The paper then considers, for each element, why it should exist, how the law currently treats it, and challenges that will shape it going forward. The paper concludes that the law should develop the right to FoT with the clear understanding that what this aims to secure is mental autonomy. This process should hence begin by establishing the core mental processes that enable mental autonomy, such as attentional and cognitive agency. The paper argues that the domain of the right to FoT should be extended to include external actions that are arguably constitutive of thought, including internet searches and diaries, hence shielding them with absolute protection. It is stressed that law must protect us from threats to FoT from both states and corporations, with governments needing to act under the positive aspect of the right to ensure societies are structured to facilitate mental autonomy. It is suggested that in order to support mental autonomy, information should be provided in autonomy-supportive contexts and friction introduced into decision making processes to facilitate second-order thought. The need for public debate about how society wishes to balance risk and mental autonomy is highlighted, and the question is raised as to whether the importance attached to thought has changed in our culture. The urgency of defending FoT is re-iterated.


Determining optical mapping errors by simulations.
Optical mapping is a complementary technology to traditional DNA sequencing technologies, such as next-generation sequencing (NGS). It provides genome-wide, high-resolution restriction maps from single, stained molecules of DNA. It can be used to detect large and small structural variants, copy number variations and complex rearrangements. Optical mapping is affected by different kinds of errors in comparison with traditional DNA sequencing technologies. It is important to understand the source of these errors and how they affect the obtained data. This article proposes a novel approach to modeling errors in the data obtained from the Bionano Genomics Inc. Saphyr system with Direct Label and Stain (DLS) chemistry. Some studies have already addressed this issue for older instruments with nicking enzymes, but we are unaware of a study that addresses this new system. The main result is a framework for studying errors in the data obtained from the Saphyr instrument with DLS chemistry. The framework's main component is a simulation that computes how major sources of errors for this instrument (a false site, a missing site and resolution errors) affect the distribution of fragment lengths in optical maps. The simulation is parametrized by variables describing these errors and we are using a differential evolution algorithm to evaluate parameters that best fit the data from the instrument. Results of the experiments manifest that this approach can be used to study errors in the optical mapping data analysis. Source codes supporting the presented results are available at: https://github.com/mvasinek/olgen-om-error-prediction. The data underlying this article are available on the Bionano Genomics Inc. website, at: https://bionanogenomics.com/library/datasets/. Supplementary data are available at Bioinformatics online.


Identification and functional analysis of NOL7 nuclear and nucleolar localization signals.
NOL7 is a candidate tumor suppressor that localizes to a chromosomal region 6p23. This locus is frequently lost in a number of malignancies, and consistent loss of NOL7 through loss of heterozygosity and decreased mRNA and protein expression has been observed in tumors and cell lines. Reintroduction of NOL7 into cells resulted in significant suppression of in vivo tumor growth and modulation of the angiogenic phenotype. Further, NOL7 was observed to localize to the nucleus and nucleolus of cells. However, the mechanisms regulating its subcellular localization have not been elucidated. An in vitro import assay demonstrated that NOL7 requires cytosolic machinery for active nuclear transport. Using sequence homology and prediction algorithms, four putative nuclear localization signals (NLSs) were identified. NOL7 deletion constructs and cytoplasmic pyruvate kinase (PK) fusion proteins confirmed the functionality of three of these NLSs. Site-directed mutagenesis of PK fusions and full-length NOL7 defined the minimal functional regions within each NLS. Further characterization revealed that NLS2 and NLS3 were critical for both the rate and efficiency of nuclear targeting. In addition, four basic clusters within NLS2 and NLS3 were independently capable of nucleolar targeting. The nucleolar occupancy of NOL7 revealed a complex balance of rapid nucleoplasmic shuttling but low nucleolar mobility, suggesting NOL7 may play functional roles in both compartments. In support, targeting to the nucleolar compartment was dependent on the presence of RNA, as depletion of total RNA or rRNA resulted in a nucleoplasmic shift of NOL7. These results identify the minimal sequences required for the active targeting of NOL7 to the nucleus and nucleolus. Further, this work characterizes the relative contribution of each sequence to NOL7 nuclear and nucleolar dynamics, the subnuclear constituents that participate in this targeting, and suggests a functional role for NOL7 in both compartments. Taken together, these results identify the requisite protein domains for NOL7 localization, the kinetics that drive this targeting, and suggest NOL7 may function in both the nucleus and nucleolus.


Response analysis of holography-based modal wavefront sensor.
The crosstalk problem of holography-based modal wavefront sensing (HMWS) becomes more severe with increasing aberration. In this paper, crosstalk effects on the sensor response are analyzed statistically for typical aberrations due to atmospheric turbulence. For specific turbulence strength, we optimized the sensor by adjusting the detector radius and the encoded phase bias for each Zernike mode. Calibrated response curves of low-order Zernike modes were further utilized to improve the sensor accuracy. The simulation results validated our strategy. The number of iterations for obtaining a residual RMS wavefront error of 0.1λ is reduced from 18 to 3.


CDCOCA: a statistical method to define complexity dependence of co-occuring chromosomal aberrations.
Copy number alterations (CNA) play a key role in cancer development and progression. Since more than one CNA can be detected in most tumors, frequently co-occurring genetic CNA may point to cooperating cancer related genes. Existing methods for co-occurrence evaluation so far have not considered the overall heterogeneity of CNA per tumor, resulting in a preferential detection of frequent changes with limited specificity for each association due to the high genetic instability of many samples. We hypothesize that in cancer some linkage-independent CNA may display a non-random co-occurrence, and that these CNA could be of pathogenetic relevance for the respective cancer. We also hypothesize that the statistical relevance of co-occurring CNA may depend on the sample specific CNA complexity. We verify our hypotheses with a simulation based algorithm CDCOCA (complexity dependence of co-occurring chromosomal aberrations). Application of CDCOCA to example data sets identified co-occurring CNA from low complex background which otherwise went unnoticed. Identification of cancer associated genes in these co-occurring changes can provide insights of cooperative genes involved in oncogenesis. We have developed a method to detect associations of regional copy number abnormalities in cancer data. Along with finding statistically relevant CNA co-occurrences, our algorithm points towards a generally low specificity for co-occurrence of regional imbalances in CNA rich samples, which may have negative impact on pathway modeling approaches relying on frequent CNA events.


Simple apparatus for pulsed electric dichroism measurements.
A novel method of measuring the electrically induced dichroism of macromolecular solutions is described. Transient changes in the solution absorption are recorded when the solute molecules are aligned by pulsed electric fields that are applied along the incident path. Previous methods have applied fields transverse to the optical beam which has had to be variably polarized. The present longitudinal arrangement needs no polarizer, is simpler, can yield the required information in a single suitable measurement, and has other distinct advantages over the former transverse arrangements. The theory for the effect is derived, and the interrelation of these novel longitudinal measurements with the conventional transverse data is verified by measurements on an aqueous solution of the amylose triiodide complex.


The risk of switch to mania in patients with bipolar disorder during treatment with an antidepressant alone and in combination with a mood stabilizer.
This study examined the risk of antidepressant-induced manic switch in patients with bipolar disorder treated either with antidepressant monotherapy or with an antidepressant in conjunction with a mood stabilizer. Using Swedish national registries, the authors identified 3,240 patients with bipolar disorder who started treatment with an antidepressant and had no antidepressant treatment during the previous year. Patients were categorized into those receiving antidepressant monotherapy and those receiving an antidepressant plus a mood stabilizer. A within-individual design was used to control for confounding by disorder severity, genetic makeup, and early environmental factors. Cox regression analyses conditioned on individual were used to compare the rate of mania 0-3 months and 3-9 months after the start of antidepressant treatment with a preceding non-treatment period. Nearly 35% of the patients were treated with antidepressant monotherapy. The increased risk of treatment-emergent mania was confined to patients on antidepressant monotherapy (hazard ratio=2.83, 95% CI=1.12, 7.19). Among patients treated with a concurrent mood stabilizer, no acute change in risk of mania was observed during the 3 months after the start of antidepressant treatment (hazard ratio=0.79, 95% CI=0.54, 1.15), and a decreased risk was observed during the period 3-9 months after treatment initiation (hazard ratio=0.63, 95% CI=0.42, 0.93). In this national registry study, antidepressant monotherapy was associated with an increased risk of mania. However, no risk of mania was seen in patients receiving an antidepressant while treated with a mood stabilizer. The results highlight the importance of avoiding antidepressant monotherapy in the treatment of bipolar disorder.


Dynamic foot pressure and other studies as diagnostic and management aids in diabetic neuropathy.
The pressures and loads under the feet during walking have been compared in three groups of 41 patients each, using a microprocessor-controlled optical system. Group A consisted of patients with diabetic neuropathy, group B of non-neuropathic diabetic patients, and group C of nondiabetic controls. Thirteen patients in group A had a history of neuropathic foot ulceration. Other investigations in the diabetic patients included motor conduction velocity (MCV) in the median and peroneal nerves, vibration perception threshold (VPT) in the great toes, the valsalva response (VR), skin resistance (SR), and the ankle pressure index (API). Fifty-one percent of neuropathic feet had abnormally high pressures underneath the metatarsal heads compared with 17% of the diabetic controls and 7% of nondiabetic subjects. All those feet with previous ulceration had abnormally high pressures at the ulcer sites. Of the other investigations, the VPT correlated most significantly with the presence of foot ulceration. In addition, a low median and peroneal nerve MCV, an abnormal VR, a high API, and the absence of sweating all correlated with the presence of foot ulceration. We therefore conclude that simple bedside investigations, such as measurement of the VPT alone, may be useful in identifying those patients at risk of foot ulceration. Foot pressure studies may then be used in such patients as a predictive and management aid by determining specific areas under the foot that are prone to ulceration.


Modelling visual neglect: computational insights into conscious perception.
Visual neglect is an attentional deficit typically resulting from parietal cortex lesion and sometimes frontal lesion. Patients fail to attend to objects and events in the visual hemifield contralateral to their lesion during visual search. The aim of this work was to examine the effects of parietal and frontal lesion in an existing computational model of visual attention and search and simulate visual search behaviour under lesion conditions. We find that unilateral parietal lesion in this model leads to symptoms of visual neglect in simulated search scan paths, including an inhibition of return (IOR) deficit, while frontal lesion leads to milder neglect and to more severe deficits in IOR and perseveration in the scan path. During simulations of search under unilateral parietal lesion, the model's extrastriate ventral stream area exhibits lower activity for stimuli in the neglected hemifield compared to that for stimuli in the normally perceived hemifield. This could represent a computational correlate of differences observed in neuroimaging for unconscious versus conscious perception following parietal lesion. Our results lead to the prediction, supported by effective connectivity evidence, that connections between the dorsal and ventral visual streams may be an important factor in the explanation of perceptual deficits in parietal lesion patients and of conscious perception in general.


A transmembrane helix dimer: structure and implications.
The three-dimensional structure of the dimeric transmembrane domain of glycophorin A (GpA) was determined by solution nuclear magnetic resonance spectroscopy of a 40-residue peptide solubilized in aqueous detergent micelles. The GpA membrane-spanning alpha helices cross at an angle of -40 degrees and form a small but well-packed interface that lacks intermonomer hydrogen bonds. The structure provides an explanation for the previously characterized sequence dependence of GpA dimerization and demonstrates that van der Waals interactions alone can mediate stable and specific associations between transmembrane helices.


Characterization of Rhizoctonia spp. Recovered from Crop Plants Used in Rotational Cropping Systems in the Western Cape Province of South Africa.
Isolates of Rhizoctonia spp. associated with barley, canola, clover, lucerne, lupin, annual Medicago spp. (medic), and wheat were recovered during the conduct of a 4-year (2000 to 2003) crop rotation trial in the Western Cape province of South Africa. These isolates were characterized by determining their anastomosis group (AG), in vitro optimum growth temperature, and pathogenicity toward emerging and 14-day-old seedlings of all the aforementioned crops. During the 4-year rotational trial, 428 Rhizoctonia isolates, in all, were obtained. The most abundant multinucleate AG was AG-4 HG-II (69%), followed by AG-2-1 (19%), AG-3 (8%), AG-2-2 (2%), and AG-11 (2%). The population of binucleate Rhizoctonia spp. comprised AG-K (53%), AG-A (10%), AG-I (5%), and unidentified AGs (32%). The optimal time for isolating Rhizoctonia spp. was found to be at the flowering or seedpod stage (20 to 22 weeks after planting). Temperature studies showed that isolates belonging to AG-2-2, AG-4 HG-II, and AG-K had significantly higher optimum growth temperatures than those from other AGs. In pathogenicity assays conducted on emerging as well as 14-day-old seedlings, isolates of AG-2-2 and AG-4 HG-II were the most virulent on all crops. Rhizoctonia solani AG-2-1 was highly virulent on canola, moderately virulent on medic and lupin, weakly virulent on lucerne and barley, and nonpathogenic on wheat. AG-11 isolates were moderate to weakly virulent on all crops, with the exception of barley and wheat. AG-3 was weakly virulent on canola, lupin, and medic. AG-K was the only binucleate Rhizoctonia sp. capable of inciting disease in our assays. This is the first comprehensive study to elucidate the identity and potential importance of Rhizoctonia spp. as a yield limiting factor in crop production systems in the Western Cape province of South Africa.


All Cause Chronic Widespread Pain is Common in Patients with Symptomatic Peripheral Arterial Disease and is Associated with Reduced Health Related Quality of Life.
Invasive treatment of peripheral arterial disease (PAD) does not always lead to improvement, as concomitant diseases might affect walking ability and health related quality of life (HRQoL). Patients with chronic widespread pain (CWP) report worse outcome when treated for cancer and rheumatic diseases. The aim of the present study was to evaluate the prevalence of CWP and its potential association with reduced HRQoL in patients treated for PAD. This was a longitudinal cohort study conducted between May 2011 and April 2014, including patients with planned invasive treatment of symptomatic PAD at two vascular clinics in Sweden. In 240 patients with planned treatment of PAD, HRQoL and pain distribution were assessed using the Short Form 36 Health Survey (SF-36), EuroQoL 5 dimensions (EQ5D), Walking Impairment Questionnaire (WIQ), and a questionnaire concerning musculoskeletal pain (Epipain manikin) before and 12 months after treatment. HRQoL was compared in patients with no chronic pain (NCP), with chronic regional pain (CRP), and with CWP. The SF-36 subscales PF, VT, and MH, representing important aspects of HRQoL (physical function, vitality, and mental health), were the main outcome measures. Before treatment 22 (10%) patients reported NCP, 133 (61%) CRP, and 64 (29%) CWP. These proportions did not differ between patients with intermittent claudication (IC) and critical limb ischemia (CLI, p = .150). CWP was more common in women than in men (36% vs. 24%, p = .035.) HRQoL improved significantly after treatment in all groups, but was still significantly reduced in CWP patients. CWP predicted worse outcome in HRQoL after treatment. CWP is common and is strongly associated with reduced HRQoL in patients with PAD. Treatment led to significant improvement, but patients with CWP still had significantly reduced HRQoL after treatment. CWP measured by a pain manikin should therefore be taken into account when evaluating disease severity, treatment options, and effect of treatment in PAD.


Human Miro Proteins Act as NTP Hydrolases through a Novel, Non-Canonical Catalytic Mechanism.
Mitochondria are highly dynamic organelles that play a central role in multiple cellular processes, including energy metabolism, calcium homeostasis and apoptosis. Miro proteins (Miros) are "atypical" Ras superfamily GTPases that display unique domain architecture and subcellular localisation regulating mitochondrial transport, autophagy and calcium sensing. Here, we present systematic catalytic domain characterisation and structural analyses of human Miros. Despite lacking key conserved catalytic residues (equivalent to Ras Y32, T35, G60 and Q61), the Miro N-terminal GTPase domains display GTPase activity. Surprisingly, the C-terminal GTPase domains previously assumed to be "relic" domains were also active. Moreover, Miros show substrate promiscuity and function as NTPases. Molecular docking and structural analyses of Miros revealed unusual features in the Switch I and II regions, facilitating promiscuous substrate binding and suggesting the usage of a novel hydrolytic mechanism. The key substitution in position 13 in the Miros leads us to suggest the existence of an "internal arginine finger", allowing an unusual catalytic mechanism that does not require GAP protein. Together, the data presented here indicate novel catalytic functions of human Miro atypical GTPases through altered catalytic mechanisms.


Enhanced vaccine control of epidemics in adaptive networks.
We study vaccine control for disease spread on an adaptive network modeling disease avoidance behavior. Control is implemented by adding Poisson-distributed vaccination of susceptibles. We show that vaccine control is much more effective in adaptive networks than in static networks due to feedback interaction between the adaptive network rewiring and the vaccine application. When compared to extinction rates in static social networks, we find that the amount of vaccine resources required to sustain similar rates of extinction are as much as two orders of magnitude lower in adaptive networks.


Cationic antimicrobial peptides disrupt the Streptococcus pyogenes ExPortal.
Although they possess a well-characterized ability to porate the bacterial membrane, emerging research suggests that cationic antimicrobial peptides (CAPs) can influence pathogen behaviour at levels that are sublethal. In this study, we investigated the interaction of polymyxin B and human neutrophil peptide (HNP-1) with the human pathogen Streptococcus pyogenes. At sublethal concentrations, these CAPs preferentially targeted the ExPortal, a unique microdomain of the S. pyogenes membrane, specialized for protein secretion and processing. A consequence of this interaction was the disruption of ExPortal organization and a redistribution of ExPortal components into the peripheral membrane. Redistribution was associated with inhibition of secretion of certain toxins, including the SpeB cysteine protease and the streptolysin O (SLO) cytolysin, but not SIC, a protein that protects S. pyogenes from CAPs. These data suggest a novel function for CAPs in targeting the ExPortal and interfering with secretion of factors required for infection and survival. This mechanism may prove valuable for the design of new types of antimicrobial agents to combat the emergence of antibiotic-resistant pathogens.


Defective DNA Mismatch Repair Influences Expression of Endometrial Carcinoma Biomarkers.
Endometrial endometrioid carcinomas are related to estrogen excess and express estrogen and progesterone receptors. However, hormone receptor expression can be variable from tumor to tumor, and this variability is not always explained by differences in tumor grade. Variable expression of other biomarkers that may be used in the diagnostic work-up of endometrial cancer has also been noted. We hypothesized that mismatch repair (MMR) defects may contribute to this variability. A total of 411 unselected endometrial carcinomas were evaluated for immunohistochemical expression of DNA MMR proteins and MLH1 methylation. Loss of immunohistochemical expression of MLH1, MSH2, MSH6, or PMS2 was defined as MMR deficient; positive expression was defined as MMR intact. A case-control cohort of 80 Grade 2 endometrioid carcinomas was selected from this set (40 MMR deficient, 40 MMR intact). Cases were matched for histotype, grade, and age. Estrogen receptor, progesterone receptor, CK7(+), CK20, and Pax-8 immunohistochemistry was evaluated. The median percentage of CK7 tumor cells was significantly lower in the MMR deficient group compared with the MMR intact group. The mean percentage of tumor cells exhibiting estrogen receptor expression was similar in both the MMR-deficient and MMR intact groups. However, there was greater variability in the MMR-deficient group. Our study shows that MMR defects influence the expression of clinically important biomarkers for endometrioid-type endometrial carcinoma as decreased cytokeratin 7 expression is more commonly associated with MMR deficiency.


Diet quality indices and risk of metabolic syndrome among postmenopausal women of Mexican ethnic descent in the Women's Health Initiative Observational Study.
The prevalence of metabolic syndrome is higher among minority populations, including individuals of Mexican ethnic descent. Whether alignment to healthy dietary patterns is associated with lower risk of metabolic syndrome in this population is largely unknown. To prospectively evaluate the associations between a priori diet quality scores and risk of metabolic syndrome and its components among postmenopausal women of Mexican ethnic descent. A total of 334 women of Mexican ethnic descent who participated in the Women's Health Initiative (WHI) observational study without metabolic syndrome or diabetes at baseline (1993-1998) were included. Baseline diets were scored with the Alternate Mediterranean Diet (aMED), the Dietary Approaches to Stop Hypertension (DASH), the Healthy Eating Index (HEI-2010), the Mediterranean Diet Score (MDS), and the traditional Mexican Diet (MexD) score. Multivariable linear and logistic regression models were used to test the associations between baseline diet quality and risk of metabolic syndrome and its individual components at follow-up (2012-2013). Approximately 16% of women met the criteria for metabolic syndrome at follow-up. None of the diet quality indices were associated with risk of metabolic syndrome. However, higher vs lower DASH scores were associated with lower waist circumference (85.2 vs 88.0 cm) and glucose concentrations (90.0 vs 95.1 mg/dL), and higher HDL cholesterol (62.6 vs 59.0 mg/dL), while higher vs lower HEI-2010 scores were associated with lower waist circumference (83.9 vs 88.1 cm), triglycerides (103 vs 117 mg/dL) and glucose concentrations (89.5 vs 94.4 mg/dL), and higher HDL cholesterol levels (63.9 vs 58.5 mg/dL). Diet quality was not associated with risk of metabolic syndrome in this population. However, the results suggest that alignment to DASH and HEI-2010 recommendations may be beneficial for reducing some individual components of metabolic syndrome among postmenopausal women of Mexican descent.


Effectiveness of massage therapy for shoulder pain: a systematic review and meta-analysis.
[Purpose] This study performed an effect-size analysis of massage therapy for shoulder pain. [Subjects and Methods] The database search was conducted using PubMed, CINAHL, Embase, PsycINFO, RISS, NDSL, NANET, DBpia, and KoreaMed. The meta-analysis was based on 15 studies, covering a total of 635 participants, and used a random effects model. [Results] The effect size estimate showed that massage therapy had a significant effect on reducing shoulder pain for short-term efficacy (SMD: -1.08, 95% CI: -1.51 to -0.65) and for long-term efficacy (SMD: -0.47, 95% CI: -0.71 to -0.23). [Conclusion] The findings from this review suggest that massage therapy is effective at improving shoulder pain. However, further research is needed, especially a randomized controlled trial design or a large sample size, to provide evidence-based recommendations.


Changes in conduction velocity during acute ischemia in ventricular myocardium of the isolated porcine heart.
Conduction velocities along longitudinal (vL) and transverse (vT) fiber axes were determined in isolated porcine hearts from subepicardial activation patterns that were produced by local stimulation and measured with a multiterminal electrode. In some of the experiments extracellular [K+] ([K+]o) and transmembrane potentials were recorded. During normal perfusion vL and vT were (cm/sec) 50.08 +/- 2.13, (SE) and 21.08 +/- 0.97. After 3 to 5 min of global ischemia, vL and vT decreased to approximately 30 and 13 cm/sec. Before the occurrence of total inexcitability propagation became time dependent 2: 1 block developed and centrifugal spread from the stimulus site was partially blocked at short intervals and was normal at long intervals. This suggested that slowed conduction was dependent on spatial nonuniformities of recovery from excitability. Slowing of conduction during ischemia was not explained by accumulation of [K+]o alone, because vL and vT at a given [K+]o were lower during ischemia than during perfusion with elevated K+. In hearts perfused at 20 mM [K+]o "slow responses" were produced by addition of epinephrine (2.5 X 10(-5)M). Resting membrane potentials of slow responses were significantly lower than of depressed action potentials during ischemia. The values vL and vT of slow responses (10 and 5 cm/sec) were much lower than the lowest values during ischemia (20 and 10 cm/sec). This indicates that slow conduction in ischemia is associated with depressed action potentials initiated by a partially inactivated rapid Na+ inward current. The time dependence of nonuniform propagation and the relatively high conduction velocities explain two major characteristics of reentrant tachycardias in acute ischemia: the large diameters of reentrant circuits and the beat-to-beat changes in localization of conduction block.


Haptic recognition of static and dynamic expressions of emotion in the live face.
If humans can detect the wealth of tactile and haptic information potentially available in live facial expressions of emotion (FEEs), they should be capable of haptically recognizing the six universal expressions of emotion (anger, disgust, fear, happiness, sadness, and surprise) at levels well above chance. We tested this hypothesis in the experiments reported here. With minimal training, subjects' overall mean accuracy was 51% for static FEEs (Experiment 1) and 74% for dynamic FEEs (Experiment 2). All FEEs except static fear were successfully recognized above the chance level of 16.7%. Complementing these findings, overall confidence and information transmission were higher for dynamic than for corresponding static faces. Our performance measures (accuracy and confidence ratings, plus response latency in Experiment 2 only) confirmed that happiness, sadness, and surprise were all highly recognizable, and anger, disgust, and fear less so.


Fractures of the lateral process of the talus: a clinical review. "Snowboarder's ankle".
This is a review article discussing the incidence, aetiology, investigation, and management of fractures of the lateral process of the talus, an uncommon but increasingly recognised complication of snowboarding. The data regarding aetiology, investigation, and management of these fractures were obtained through a comprehensive literature review utilising the Medline, Sport discus, Medline Orthopaedic, and Cinahl databases. Injury data were obtained through published prospective epidemiological studies of snowboarding injuries. All studies of talar fractures, particularly of the lateral process, were included in the review. All prospective and retrospective studies of snowboarding injuries were reviewed. The mechanism of this injury appears to be a combination of dorsiflexion and inversion of the ankle. The combination of soft-shell snowboarding boots and aerial maneuvers increase the likelihood of injury. Clinically these injuries resemble severe ligamentous ankle sprains and are commonly misdiagnosed. The fractures can be classified into three subtypes based on the severity of the bony injury. The management of each injury subtype differs and although no prospective treatment trials have been performed the published risk of long term degenerative subtalar joint damage warrant aggressive early management of this injury. With the increasing popularity of snowboarding, the possibility of this injury should be considered in all ankle injuries related to this sport. Once diagnosed, management guidelines should be followed in order to minimise long term problems.


Inhibition of Schwann cell myelination in vitro by antibody to the L1 adhesion molecule.
The specific axonal and Schwann cell surface molecules that mediate the initiation of myelination have not been identified. We have used cocultures of purified rat dorsal root ganglion neurons and Schwann cells and purified polyclonal antibodies to the L1 adhesion molecule to study the role of L1 in myelin formation. Schwann cells were first arrested in a basal-lamina-free premyelination stage (by serum/ascorbate deprivation), then manipulated to allow basal lamina deposition and myelination (by serum/ascorbate addition) in the absence or presence of anti-L1. Using electron microscopy, immunocytochemistry, and myelin sheath quantitation after Sudan-black staining, we determined the effect of anti-L1 on (1) basal lamina formation, (2) the segregation by Schwann cells of axons into a 1:1 relationship, (3) galactocerebroside (Gal-C) expression, (4) laminin deposition, and (5) myelin formation. Anti-L1 strongly blocked myelin formation, Gal-C expression, and axon segregation but did not block basal lamina formation. In controls, elongated Schwann cell processes completely covered the axons and exhibited uniform surface staining for laminin; in anti-L1-treated cultures, shortened Schwann cells, intensely stained for laminin, were observed in clusters separated by unstained lengths of axons. When 50 micrograms/ml exogenous purified laminin was added to the medium, Schwann cell length and laminin staining were similar in control and treated cultures. However, the inhibition of myelination of anti-L1 was not altered by the addition of laminin. Myelination was also inhibited with antigen-binding fragments (Fab) of polyclonal anti-L1, but an antibody to liver membranes did not block myelination. These results indicate that L1 is involved in the linear extension of Schwann cell processes along axons, the engulfment of axons, and the induction of myelin-specific components within the Schwann cell. We conclude that anti-L1 prevents myelination by blocking these events rather than by blocking basal lamina deposition.


Positive Response to Bilateral Sinusoidal ECT in Unilateral and Bilateral Brief-pulse "ECT-Resistant" Depressive Illness.
Six patients who failed to respond to what would ordinarily be considered therapeutically effective courses of sequential unilateral nondominant (mean number 10) and bilateral brief-pulse electroconvulsive therapy (ECT) (mean number 10) with electroencephalographic (EEG) monitoring of seizure duration (all seizures >30 s) subsequently received courses of bilateral sinusoidal ECT (mean number 6) and responded well. Some theoretical implications and clinical considerations raised by these cases are discussed.


Influence of basement membrane proteins and endothelial cell-derived factors on the morphology of human fetal-derived astrocytes in 2D.
Astrocytes are the most prevalent type of glial cell in the brain, participating in a variety of diverse functions from regulating cerebral blood flow to controlling synapse formation. Astrocytes and astrocyte-conditioned media are widely used in models of the blood-brain barrier (BBB), however, very little is known about astrocyte culture in 2D. To test the hypothesis that surface coating and soluble factors influence astrocyte morphology in 2D, we quantitatively analyzed the morphology of human fetal derived astrocytes on glass, matrigel, fibronectin, collagen IV, and collagen I, and after the addition soluble factors including platelet-derived growth factor (PDGF), laminin, basic fibroblast growth factor (bFGF), and leukemia inhibitory factor (LIF). Matrigel surface coatings, as well as addition of leukemia inhibitory factor (LIF) to the media, were found to have the strongest effects on 2D astrocyte morphology, and may be important in improving existing BBB models. In addition, the novel set of quantitative parameters proposed in this paper provide a test for determining the influence of compounds on astrocyte morphology, both to screen for new endothelial cell-secreted factors that influence astrocytes, and to determine in a high-throughput way which factors are important for translation to more complex, 3D BBB models.


Family income, parenting styles and child behavioural-emotional outcomes.
A positive relationship between income and child outcomes has been observed in data from numerous countries. A key question concerns the extent to which this association represents a causal relationship as opposed to unobserved heterogeneity. We use data from the National Longitudinal Survey of Children and Youth to implement a series of empirical strategies for estimating the existence and size of the effect of income on behavioural-emotional outcomes. We also examine the role of parenting style. Our results indicate that there is little evidence of an effect of income on behavioural-emotional scores. The exclusion of parenting style from the models was found to not bias the estimated income effect, but parenting style was found to have a consistent impact on child outcomes.


The Relative Importance of Post-Acute Care and Readmissions for Post-Discharge Spending.
To understand what patterns of health care use are associated with higher post-hospitalization spending. Medicare hospital, skilled nursing, inpatient rehabilitation, and home health agency claims, and Medicare enrollment data from 2007 and 2008. For 10 common inpatient conditions, we calculated variation across hospitals in price-standardized and case mix-adjusted Medicare spending in the 30 days following hospital discharge. We estimated the fraction of spending differences between low- and high-spending hospitals attributable to readmissions versus post-acute care, and within post-acute care between inpatient rehabilitation facility (IRF) versus skilled nursing facility (SNF) use. For each service, we distinguished between differences in probability of use and spending conditional on use. We identified index hospital claims and examined hospital and post-acute care occurring within a 30-day period following hospital discharge. For each Medicare Severity Diagnosis-Related Group (MS-DRG) at each hospital, we calculated average price-standardized Medicare payments for readmissions, SNFs, IRFs, and post-acute care overall (also including home health agencies and long-term care hospitals). There was extensive variation across hospitals in Medicare spending in the 30 days following hospital discharge. For example, the interquartile range across hospitals ranged from $1,245 for chronic obstructive pulmonary disease to over $4,000 for myocardial infarction MS-DRGs. The proportion of differences attributable to readmissions versus post-acute care differed across conditions. For myocardial infarction, 74 to 93 percent of the variation was due to readmissions. For hip and femur procedures and joint replacement, 72 to 92 percent of the variation was due to differences in post-acute care spending. There was also variation in the relative importance of the type of post-acute spending. For hip and femur procedures, joint replacement, and stroke, whether patients received IRF was the key driver of variation in post-acute care spending In contrast, for pneumonia and heart failure, whether patients received SNF care was the key driver of variation in post-acute spending. Through initiatives such as bundled payment, hospitals are financially responsible for spending in the post-hospitalization period. The key driver of variation in post-hospitalization spending varied greatly across conditions. For some conditions, the key driver was having a readmission, for others it was whether patients receive any post-acute care, and for others the key driver was the type of post-acute care. These findings may help hospitals implement strategies to reduce post-discharge spending.


PRMT5-mediated histone H4 arginine-3 symmetrical dimethylation marks chromatin at G + C-rich regions of the mouse genome.
Symmetrical dimethylation on arginine-3 of histone H4 (H4R3me2s) has been reported to occur at several repressed genes, but its specific regulation and genomic distribution remained unclear. Here, we show that the type-II protein arginine methyltransferase PRMT5 controls H4R3me2s in mouse embryonic fibroblasts (MEFs). In these differentiated cells, we find that the genome-wide pattern of H4R3me2s is highly similar to that in embryonic stem cells. In both the cell types, H4R3me2s peaks are detected predominantly at G + C-rich regions. Promoters are consistently marked by H4R3me2s, independently of transcriptional activity. Remarkably, H4R3me2s is mono-allelic at imprinting control regions (ICRs), at which it marks the same parental allele as H3K9me3, H4K20me3 and DNA methylation. These repressive chromatin modifications are regulated independently, however, since PRMT5-depletion in MEFs resulted in loss of H4R3me2s, without affecting H3K9me3, H4K20me3 or DNA methylation. Conversely, depletion of ESET (KMT1E) or SUV420H1/H2 (KMT5B/C) affected H3K9me3 and H4K20me3, respectively, without altering H4R3me2s at ICRs. Combined, our data indicate that PRMT5-mediated H4R3me2s uniquely marks the mammalian genome, mostly at G + C-rich regions, and independently from transcriptional activity or chromatin repression. Furthermore, comparative bioinformatics analyses suggest a putative role of PRMT5-mediated H4R3me2s in chromatin configuration in the nucleus.


Characterization of the iron oxide phases formed during the synthesis of core-shell FexOy@C nanoparticles modified with Ag.
Core-shell FexOy@C nanoparticles (NPs) modified with Ag were studied with x-ray diffraction, transmission electron microscopy, energy dispersive elemental mapping, Mössbauer spectroscopy, static magnetic measurements, and optical magnetic circular dichroism (MCD). FexOy@C NPs synthesized by the pyrolysis process of the mixture of Fe(NO3)3 · 9H2O with oleylamine and oleic acid were added to a heated mixture of oleylamine and AgNO3 in different concentrations. The final product was a mixture of iron oxide crystalline NPs in an amorphous carbon shell and Ag crystalline NPs. The iron oxide NPs were presented by two magnetic phases with extremely close crystal structures: Fe3O4 and γ-Fe2O3. Ag is shown to form crystalline NPs located very close to the iron oxide NPs. An assumption is made about the formation of hybrid FexOy@C-Ag NPs. Correlations were obtained between the Ag concentration in the fabricated samples, their magnetic properties and the MCD spectrum shape. Introducing Ag led to a approximately linear decrease of the NPs saturation magnetization depending upon the Ag concentration, it also resulted into the MCD spectrum shift to the lower light wave energies. MCD was also studied for the Fe3O4@C NPs synthesized earlier with the same one-step process using different heat treatment temperatures, and MCD spectra were compared for two series of NPs. A possible contribution of the surface plasmon excitation in Ag NPs to the MCD spectrum of the FexOy@C-Ag NPs is discussed.


Virtual and Augmented Reality in Cardiac Surgery.
Virtual and augmented reality can be defined as a three-dimensional real-world simulation allowing the user to directly interact with it. Throughout the years, virtual reality has gained great popularity in medicine and is currently being adopted for a wide range of purposes. Due to its dynamic anatomical nature, permanent drive towards decreasing invasiveness, and strive for innovation, cardiac surgery depicts itself as a unique environment for virtual reality. Despite substantial research limitations in cardiac surgery, the current literature has shown great applicability of this technology, and promising opportunities.


Pseudoexfoliation syndrome, a systemic disorder with ocular manifestations.
Pseudoexfoliation syndrome (PXS) is a systemic condition with eye manifestations. In the eye, pseudoexfoliation material deposits on various structures of the anterior segment. The nature of this material is mostly fibrillar with fibers made up of microfibrils and coated with amorphous material. The composition of these fibrils is diverse and includes basement membrane components as well as enzymes involved in extracellular matrix maintenance. Pseudoexfoliation is the most common cause of secondary open-angle glaucoma (pseudoexfoliation glaucoma, PXG) worldwide. The goal of this review is to summarize our knowledge on the genetics of this systemic disorder and its resultant ocular manifestations. PXS familial aggregation suggests genetic inheritance. PXS has been strongly associated with single nucleotide polymorphisms (SNPs) of the lysyl oxidase-like 1 (LOXL1) gene on chromosome 15q24.1. Two of these SNPs confer a higher than 99% population attributable risk for PXS and PXG in the Nordic population; however, they carry different risks in different populations. The high risk haplotypes also vary among different populations. LOXL1 is one of group of the enzymes involved in the cross-linking of collagen and elastin in the extracellular matrix. Its function in connective tissue maintenance has been confirmed in mice; however, its actual role in PXS remains unclear. Contactin-associated protein-like 2 also has a strong genetic association with PXS in a German cohort and is an attractive candidate molecule. It encodes for a protein involved in potassium channel trafficking. Other candidate genes linked to PXS include lysosomal trafficking regulator, clusterin, adenosine receptors, matrix metalloproteinase-1 (MMP1), and glutathione transferase. These genes may be modifying genes for development of PXS and PXG.


Rural African American parents' knowledge and decisions about human papillomavirus vaccination.
To identify predictors of human papillomavirus (HPV) vaccination among rural African American families. Cross-sectional descriptive study in schools in three rural counties in southeastern United States. The sample consisted of African American parents or caregivers with children 9 to 13 years of age who attended elementary or middle school in 2010-2011. Using an anonymous, 26-item survey, we collected descriptive data during parent-teacher events from African American parents with children in elementary or middle school. The main outcome was measured as a response of "yes" to the statement "I have or will vaccinate my child with the HPV vaccine." In addition, composite scores of knowledge and positive attitudes and beliefs were compared. No interventions were conducted. We identified predictors of HPV vaccination and found that religious affiliation had a correlation with vaccinating or planning to vaccinate a child. Results indicate a need for further research on the role of local culture, including religion and faith, in rural African Americans' decisions about giving their children the HPV vaccination. This study emphasizes the importance of understanding rural African American parents' knowledge, attitudes, and spiritual beliefs when designing health education programs and public health interventions to increase HPV vaccination uptake among African American boys and girls living in rural areas.


VisTA: Integrating Machine Intelligence with Visualization to Support the Investigation of Think-Aloud Sessions.
Think-aloud protocols are widely used by user experience (UX) practitioners in usability testing to uncover issues in user interface design. It is often arduous to analyze large amounts of recorded think-aloud sessions and few UX practitioners have an opportunity to get a second perspective during their analysis due to time and resource constraints. Inspired by the recent research that shows subtle verbalization and speech patterns tend to occur when users encounter usability problems, we take the first step to design and evaluate an intelligent visual analytics tool that leverages such patterns to identify usability problem encounters and present them to UX practitioners to assist their analysis. We first conducted and recorded think-aloud sessions, and then extracted textual and acoustic features from the recordings and trained machine learning (ML) models to detect problem encounters. Next, we iteratively designed and developed a visual analytics tool, VisTA, which enables dynamic investigation of think-aloud sessions with a timeline visualization of ML predictions and input features. We conducted a between-subjects laboratory study to compare three conditions, i.e., VisTA, VisTASimple (no visualization of the ML's input features), and Baseline (no ML information at all), with 30 UX professionals. The findings show that UX professionals identified more problem encounters when using VisTA than Baseline by leveraging the problem visualization as an overview, anticipations, and anchors as well as the feature visualization as a means to understand what ML considers and omits. Our findings also provide insights into how they treated ML, dealt with (dis)agreement with ML, and reviewed the videos (i.e., play, pause, and rewind).


Antiviral oseltamivir is not removed or degraded in normal sewage water treatment: implications for development of resistance by influenza A virus.
Oseltamivir is the main antiviral for treatment and prevention of pandemic influenza. The increase in oseltamivir resistance reported recently has therefore sparked a debate on how to use oseltamivir in non pandemic influenza and the risks associated with wide spread use during a pandemic. Several questions have been asked about the fate of oseltamivir in the sewage treatment plants and in the environment. We have assessed the fate of oseltamivir and discuss the implications of environmental residues of oseltamivir regarding the occurrence of resistance. A series of batch experiments that simulated normal sewage treatment with oseltamivir present was conducted and the UV-spectra of oseltamivir were recorded. Our experiments show that the active moiety of oseltamivir is not removed in normal sewage water treatments and is not degraded substantially by UV light radiation, and that the active substance is released in waste water leaving the plant. Our conclusion is that a ubiquitous use of oseltamivir may result in selection pressures in the environment that favor development of drug-resistance.


Large-scale evaluation of a single-tube nested PCR for the laboratory diagnosis of human brucellosis in Kuwait.
A single-tube nested PCR assay identifying a 52 bp fragment from the genus-specific Brucella IS711 gene was used prospectively in clinical practice for the diagnosis of human brucellosis in Kuwait. Patients with suspected brucellosis and with other infections were investigated as clinically indicated but in all of them culture, serology and PCR for Brucella were carried out. Out of 263 suspected cases of brucellosis, diagnostic tests were positive in 199, serology was positive in 199 and culture in 89, while the Brucella PCR was positive in 193 (sensitivity 96.98%, 95% confidence interval 94.5-99.5%). Chronic brucellosis, involving symptoms for more than 1 year, was diagnosed in 49 out of these 193 patients. Diagnoses in four out of the six patients with positive serology but negative PCR and culture were non-Brucella bacterial meningitis and viral meningitis. False-negative PCR results were possible in the remaining two; both had been on long-term antibiotics for previously diagnosed brucellosis but their adherence may have been questionable, allowing a relapse. The PCR was negative in 244 patients with other infections (specificity 100%) and in 180 control subjects with negative Brucella culture and serology. PCR results were available within 24 h of sample receipt, providing diagnostic information rapidly. The PCR is expensive and technically demanding and may not be appropriate for all cases. Future studies will help define how it may best be used. For example Brucella and tuberculous meningitides can be very similar, Brucella PCR may allow prompt distinction between the two, avoiding the need for prolonged empirical treatment for both.


Persistent KSHV Infection Increases EBV-Associated Tumor Formation In Vivo via Enhanced EBV Lytic Gene Expression.
The human tumor viruses Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) establish persistent infections in B cells. KSHV is linked to primary effusion lymphoma (PEL), and 90% of PELs also contain EBV. Studies on persistent KSHV infection in vivo and the role of EBV co-infection in PEL development have been hampered by the absence of small animal models. We developed mice reconstituted with human immune system components as a model for KSHV infection and find that EBV/KSHV dual infection enhanced KSHV persistence and tumorigenesis. Dual-infected cells displayed a plasma cell-like gene expression pattern similar to PELs. KSHV persisted in EBV-transformed B cells and was associated with lytic EBV gene expression, resulting in increased tumor formation. Evidence of elevated lytic EBV replication was also found in EBV/KSHV dually infected lymphoproliferative disorders in humans. Our data suggest that KSHV augments EBV-associated tumorigenesis via stimulation of lytic EBV replication.


Assessing cancer pain.
Regular assessment for the presence of pain and response to pain management strategies should be high priority in cancer patients. Pain is a multidimensional experience in cancer patients. Pain management will be most effective when treatments are individualized after exploring the various physical and non-physical components of pain, and the patient and family are educated and involved in decision making. This article discusses the various issues that are pertinent to the assessment of pain in cancer patients.


Interbase-FRET binding assay for pre-microRNAs.
The aberrant expression of microRNAs (miRs) has been linked to several human diseases. A promising approach for targeting these anomalies is the use of small-molecule inhibitors of miR biogenesis. These inhibitors have the potential to (i) dissect miR mechanisms of action, (ii) discover new drug targets, and (iii) function as new therapeutic agents. Here, we designed Förster resonance energy transfer (FRET)-labeled oligoribonucleotides of the precursor of the oncogenic miR-21 (pre-miR-21) and used them together with a set of aminoglycosides to develop an interbase-FRET assay to detect ligand binding to pre-miRs. Our interbase-FRET assay accurately reports structural changes of the RNA oligonucleotide induced by ligand binding. We demonstrate its application in a rapid, qualitative drug candidate screen by assessing the relative binding affinity between 12 aminoglycoside antibiotics and pre-miR-21. Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) were used to validate our new FRET method, and the accuracy of our FRET assay was shown to be similar to the established techniques. With its advantages over SPR and ITC owing to its high sensitivity, small sample size, straightforward technique and the possibility for high-throughput expansion, we envision that our solution-based method can be applied in pre-miRNA-target binding studies.


HLA in anthropology: the enigma of Easter Island.
In this article, we first present four significant cases where human leukocyte antigen (HLA) studies have been useful for the reconstruction of human peopling history on the worldwide scale; i.e., the spread of modern humans from East Africa, the colonization of East Asia along two geographic routes, the co-evolution of genes and languages in Africa, and the peopling of Europe through a main northward migration. These examples show that natural selection did not erase the genetic signatures of our past migrations in the HLA genetic diversity patterns observed today. In the second part, we summarize our studies on Easter Island. Using genomic HLA typing, we could trace an introduction of HLA alleles of native American (Amerindian) origin to Easter Island before the Peruvian slave trades; i.e., before the 1860s, and provide suggestive evidence that they may have already been introduced in prehistoric time. Our results give further support to an initial Polynesian population of the island, but also reveal an early contribution by Amerindians. Together, our data illustrate the usefulness of typing for HLA alleles to complement genetic analyses in anthropological investigations.


First Report of Candidatus Liberibacter asiaticus Associated with Citrus Huanglongbing in California.
Huanglongbing (HLB), also known as citrus greening, is one of the most destructive citrus diseases worldwide and is seen as a major threat to the multimillion dollar citrus industry in California. The vector of the two bacterial species associated with this disease, Candidatus Liberibacter asiaticus and Ca. L. americanus, is the Asian citrus psyllid (ACP), Diaphorina citri (4). ACP was detected in California in August of 2008 and has since been detected in nine counties in southern California. As part of a long term survey and testing program for the ACP carrying the HLB associated bacteria, groups of ACP nymphs and adults were submitted to the Jerry Dimitman Citrus Research Board/Citrus Pest and Disease Prevention Program Laboratory in Riverside, CA. In March 2012, DNA extracted using the Qiagen MagAttract 96 DNA plant kit (QIAGEN Inc., 27220 Turnberry Lane, Suite 200, Valencia, CA 91355) from a group of three ACP adults tested positive for Ca. L. asiaticus with the real-time PCR assay developed by Li et al. (4). ACP adults were collected from a residential citrus tree located in the Hacienda Heights area of Los Angeles County, California. The approximately 1.8 meter tall lemon tree had 23 graft unions, primarily of lemon (Citrus × meyeri) and pomelo (Citrus maxima) varieties. The tree was unthrifty, with yellow shoots and chlorotic leaves. Symptoms on the lemon and pomelo leaves included asymmetrical blotchy mottling, yellowing, and corking of the leaf veins, with the blotchy mottle more prominent in the pomelo leaves. Pomelo leaves appeared crinkled along the thickened veins. Lemon leaves had yellow veins and a few had islands of green tissue completely surrounded by yellow tissue. The entire tree was removed, cut into sections, bagged, and transported to the CDFA Plant Pest Diagnostics Lab for analysis. Two hundred milligrams of petiole and midrib tissue from leaves apical to each graft union was collected, and DNA from each sample was extracted using the Qiagen DNeasy plant mini kit. DNA extracted from both lemon and pomelo leaves tested positive for Ca. L. asiaticus using real-time PCR (4). A 1,160-bp fragment of the 16S ribosomal RNA gene was amplified from the insect and plant DNA extracts using conventional PCR with primers Ol1 and OI2c (2). A 703-bp fragment of the β-operon gene was amplified from the insect and plant extracts with primers A2 and J5 (1). The 16S rDNA fragments from the insect and plant respectively (GenBank Accession Nos. JX430434 and JX455745) and the β-operon fragments (JX430435 and JX455746) showed 100% identity with the corresponding regions of Ca. L. asiaticus (CP001677) strain psy 62. Our 16S rDNA sequence showed 98% identity with Ca. L. africanus (EU921620), 97% identity with Ca. L. solanacearum (HM246509), and 96% with Ca. L. americanus (FJ036892). In response to the detection of HLB, a 241 km2 quarantine area around the detection site was established. Surveys for ACP and symptomatic host plants within the HLB quarantine area are ongoing. To date, there have been no additional positive detections. In the United States, HLB was first detected in Florida in 2005 (4) and in Texas in January of 2012 (3). To our knowledge, this is the first confirmed report of Ca. L. asiaticus associated with HLB in California. References: (1) A. Hocquellet et al. Mol. Cell. Probes 13:373, 1999. (2) S. Jagoueix et al. Mol. Cell. Probes 10:43, 1996. (3) M. Kunta et al. Phytopathology 102:S4.66, 2012. (4) W. Li et al. J. Microbiol. Methods 66:104, 2006.


Efficacy of human immunodeficiency virus prevention interventions among men who have sex with men in China: a meta-analysis.
This study aimed to determine the efficacy of HIV prevention interventions among men who have sex with men (MSM) in China. Human immunodeficiency virus (HIV) knowledge, HIV testing, condom use, sexual risk activity, incidence of sexually transmitted diseases, and HIV incidence were used as outcomes. Meta-analytic techniques were used to compute and aggregate effect sizes for 22 studies, published between 2004 and 2011, which met inclusion criteria. Variables with the potential to moderate intervention efficacy were also tested. The overall mean weighted effect size was d = 0.627 (95% confidence interval [CI], 0.460-0.793; Z = 7.38; P < 0.001) for HIV knowledge, d = 0.394 (95% CI, 0.274-0.514; Z = 6.44; P < 0.001) for condom use with men, and d = 0.590 (95% CI, 0.420-0.761; Z = 6.80; P < 0.001) for HIV testing, which indicates a statistically significant impact through intervention. Statistically significant effect sizes were also found for condom use with women and for number of sexual partners. Interventions for condom use conducted in Southwest China (the region in China with the highest prevalence of HIV) were significantly less efficacious. Interventions for condom use were significantly more efficacious when the respondent-driven sampling recruitment method and popular opinion leader intervention strategy were used. Human immunodeficiency virus prevention interventions were efficacious among MSM in China. Additional efforts are needed to control the growing HIV/acquired immunodeficiency syndrome infection among MSM in China. Future interventions need to use more rigorous intervention methodologies (e.g., respondent-driven sampling method, and popular opinion leader intervention strategy).


Outpatient versus inpatient observation after percutaneous native kidney biopsy: a cost minimization study.
Percutaneous kidney biopsy (PKB) is the primary diagnostic tool for kidney disease. Outpatient 'day surgery' (ODS) following PKB in low-risk patients has previously been described as a safe alternative to inpatient observation (IO). This study aims to determine if ODS is less costly compared to IO while accounting for all institutional costs (IC) associated with post-PKB complications, including death. A cost minimization study was performed using decision analysis methodology which models relative costs in relation to outcome probabilities yielding an optimum decision. The potential outcomes included major complications (bleeding requiring blood transfusion or advanced intervention), minor complications (bleeding or pain requiring additional observation), and death. Probabilities were obtained from the published literature and a base case was selected. IC were obtained for all complications from institutional activity-based cost estimates. The base case assumed a complication rate of 10% with major bleeding occurring in 2.5% of patients (for both arms) and death in 0.1 and 0.15% of IO and ODS patients, respectively. ODS costs USD 1,394 per biopsy compared to USD 1,800 for IO inclusive of all complications. IC for ODS remain less when overall complications <20%, major complications <5.5%, and IC per death <USD 1.125 million. ODS remained favored through sensitivity analysis. Outpatient management after PKB for low-risk patients costs less from the institutional perspective compared to IO, inclusive of complications and death. ODS should be considered for low-risk patients undergoing native kidney biopsy.


K+ channel regulation of signal propagation in dendrites of hippocampal pyramidal neurons.
Pyramidal neurons receive tens of thousands of synaptic inputs on their dendrites. The dendrites dynamically alter the strengths of these synapses and coordinate them to produce an output in ways that are not well understood. Surprisingly, there turns out to be a very high density of transient A-type potassium ion channels in dendrites of hippocampal CA1 pyramidal neurons. These channels prevent initiation of an action potential in the dendrites, limit the back-propagation of action potentials into the dendrites, and reduce excitatory synaptic events. The channels act to prevent large, rapid dendritic depolarizations, thereby regulating orthograde and retrograde propagation of dendritic potentials.


Non-linear relationship between intensity of plant-animal interactions and selection strength.
The shape of the relationship between intensity of biotic interactions and strength of selection is important for spatial variation in selection, but is little explored. We quantified interactions and selection in 69 populations of the short-lived herb Primula farinosa. As predicted because of saturation and depletion effects, the strength of selection on a discrete and on a continuously varying floral display trait were in several cases significantly non-linearly related to the mean intensity of mutualistic and antagonistic interactions. Strength of selection was strongest at low levels of fruit initiation and at high intensities of seed predation. Seed predation varied more among populations than did fruit initiation and could explain a larger proportion of the among-population variation in strength of selection. Our results support the contention that interaction intensity affects selection strength, and suggests that for mutualistic and antagonistic interactions that can be saturated or depleted, this relationship is sometimes non-linear.


Reducing blood-culture contamination through an education program.
A blood culture is the cornerstone of an established etiological diagnosis of septicemia. Although it is not currently possible to eliminate blood-culture contamination, many interventions have been shown to reduce contamination rates. Retrospective data analysis through an initial audit with major departments at one hospital, including the intensive care unit and emergency department, showed that the blood-culture contamination rate was 4.8%, which is more than the set standard (ie, less than 3%). A decrease in blood-culture contamination rates from the initial 4.8% to less than 3% was obtained with a supervised training and evaluation program through collaborative efforts of the nursing and laboratory departments.


Evaluation of estimates of alveolar gas exchange by using a tidally ventilated nonhomogenous lung model.
The purpose of this study was to evaluate algorithms for estimating O2 and CO2 transfer at the pulmonary capillaries by use of a nine-compartment tidally ventilated lung model that incorporated inhomogeneities in ventilation-to-volume and ventilation-to-perfusion ratios. Breath-to-breath O2 and CO2 exchange at the capillary level and at the mouth were simulated by using realistic cyclical breathing patterns to drive the model, derived from 40-min recordings in six resting subjects. The SD of the breath-by-breath gas exchange at the mouth around the value at the pulmonary capillaries was 59.7 +/- 25.5% for O2 and 22.3 +/- 10.4% for CO2. Algorithms including corrections for changes in alveolar volume and for changes in alveolar gas composition improved the estimates of pulmonary exchange, reducing the SD to 20.8 +/- 10.4% for O2 and 15.2 +/- 5.8% for CO2. The remaining imprecision of the estimates arose almost entirely from using end-tidal measurements to estimate the breath-to-breath changes in end-expiratory alveolar gas concentration. The results led us to suggest an alternative method that does not use changes in end-tidal partial pressures as explicit estimates of the changes in alveolar gas concentration. The proposed method yielded significant improvements in estimation for the model data of this study.


Photophysical properties of xanthophylls in carotenoproteins from human retinas.
The macula of the human retina contains high amounts of the xanthophyll carotenoids lutein and zeaxanthin [a mixture of (3R,3'R)-zeaxanthin and (3R,3'S-meso)-zeaxanthin]. Recently, it was shown that the uptake and the stabilization of zeaxanthin and lutein into the retina are likely to be mediated by specific xanthophyll-binding proteins (XBP). Here, we have used femtosecond pump-probe spectroscopy to study the dynamics of the S1 state of these xanthophylls in xanthophyll-enriched and native XBP. The results from the native XBP and the enriched XBP were then compared with those for carotenoids in organic solvents and in detergent micelles. Steady-state and transient absorption spectra show that the incorporation of xanthophylls into the protein causes a redshift of the spectra, which is stronger for lutein than for zeaxanthin. The transient absorption spectra further indicate that a part of the xanthophylls remains unbound in the xanthophyll-enriched XBP. The transient absorption spectra of the native XBP prove the presence of both xanthophylls in native XBP. Although the S1 lifetime of lutein does not exhibit any changes when measured in solution, micelles or XBP, we have observed the influence of the environment on the S1 lifetime of meso-zeaxanthin, which has a longer (12 ps) lifetime in XBP than in solution (9 ps). The most pronounced effect was found for vibrational relaxation in the S1 state, which is significantly slower for xanthophylls in XBP compared with micelles and solution. This effect is more pronounced for meso-zeaxanthin, suggesting a specific site of binding of this carotenoid to XBP.


Assessment of patient dose and noise level of clinical CT images: automated measurements.
We investigated comparisons between patient dose and noise in pelvic, abdominal, thoracic and head CT images using an automatic method. 113 patient images (37 pelvis, 34 abdominal, 25 thoracic, and 17 head examinations) were retrospectively and automatically examined in this study. Water-equivalent diameter (Dw), size-specific dose estimates (SSDE) and noise were automatically calculated from the center slice for every patient image. The Dw was calculated based on auto-contouring of the patients' edges, and the SSDE was calculated as the product of the volume CT dose index (CTDIvol) extracted from the Digital Imaging and Communications in Medicine (DICOM) header and the size conversion factor based on the Dw obtained from AAPM 204. The noise was automatically measured as a minimum standard deviation in the map of standard deviations. A square region of interest of about 1 cm2 was used in the automated noise measurement. The SSDE values for the pelvis, abdomen, thorax, and head were 21.8 ± 7.3 mGy, 22.0 ± 4.5 mGy, 21.5 ± 4.7 mGy, and 65.1 ± 1.7 mGy, respectively. The SSDEs for the pelvis, abdomen, and thorax increased linearly with increasing Dw, and for the head with constant tube current, the SSDE decreased with increasing Dw. The noise in the pelvis, abdomen, thorax, and head were 5.9 ± 1.5 HU, 5.2 ± 1.4 HU, 4.9 ± 0.8 HU and 3.9 ± 0.2 HU, respectively. The noise levels for the pelvis, abdomen, and thorax of the patients were relatively constant with Dw because of tube current modulation. The noise in the head image was also relatively constant because Dw variations in the head are very small. The automated approach provides a convenient and objective tool for dose optimizations.


A follow-up of some north-east London trainees.
General practitioner trainees from the period 1963-80 were followed up with a postal questionnaire, yielding a 62 per cent response rate. Questions were asked about their training and their current posts. Of the ex-trainees, 62 per cent were graduates from overseas medical schools, 92 per cent were now general practitioner principals in the United Kingdom and 25 per cent had experienced difficulty in finding a practice. Trainees from a three-year vocational training scheme (VTS), predominantly from UK medical schools, scored higher on an Index of Attainment than those not from a VTS. Sixty-three per cent of trainees had settled within 10 miles of training area. Only 27 per cent of trainees now worked in a health centre, compared with 61 per cent of trainers. Comments on the training programme suggested financial matters were inadequately dealt with. Twelve per cent would have preferred a longer period in the training practice and 18 per cent made negative comments about their training.


Toward a Rapid Production of Multivirus-Specific T Cells Targeting BKV, Adenovirus, CMV, and EBV from Umbilical Cord Blood.
Umbilical cord blood (CB) has emerged as an effective alternative donor source for hematopoietic stem cell transplantation. Despite this success, the prolonged duration of immune suppression following CB transplantation and the naiveté of CB T cells leave patients susceptible to viral infections. Adoptive transfer of ex vivo-expanded virus-specific T cells from CB is both feasible and safe. However, the manufacturing process of these cells is complicated, lengthy, and labor-intensive. We have now developed a simplified method to manufacture a single culture of polyclonal multivirus-specific cytotoxic T cells in less than 30 days. It eliminates the need for a live virus or transduction with a viral vector, thus making this approach widely available and GMP-applicable to target multiple viruses. The use of overlapping PepMixes as a source of antigen stimulation enable expansion of the repertoire of the T cell product to any virus of interest and make it available as a third party "off the shelf" treatment for viral infections following transplantation.


Efficacy and safety of weekly alendronate plus vitamin D₃ 5600 IU versus weekly alendronate alone in Korean osteoporotic women: 16-week randomized trial.
Vitamin D (vit-D) is essential for bone health, although many osteoporosis patients have low levels of 25-hydroxy-vit-D [25(OH)D]. This randomized, open-label study compared the effects of once weekly alendronate 70 mg containing 5600 IU vit-D₃ (ALN/D5600) to alendronate 70 mg without additional vit-D (ALN) on the percent of patients with vit-D insufficiency [25(OH)D <15 ng/mL, primary endpoint] and serum parathyroid hormone (PTH, secondary endpoint) levels in postmenopausal, osteoporotic Korean women. Neuromuscular function was also measured. A total of 268 subjects were randomized. Overall, 35% of patients had vit-D insufficiency at baseline. After 16-weeks, there were fewer patients with vit-D insufficiency in the ALN/D5600 group (1.47%) than in the ALN group (41.67%) (p<0.001). Patients receiving ALN/D5600 compared with ALN were at a significantly decreased risk of vit-D insufficiency [odds ratio=0.02, 95% confidence interval (CI) 0.00-0.08]. In the ALN/D5600 group, significant increases in serum 25(OH)D were observed at weeks 8 (9.60 ng/mL) and 16 (11.41 ng/mL), where as a significant decrease was recorded in the ALN group at week 16 (-1.61 ng/mL). By multiple regression analysis, major determinants of increases in serum 25(OH)D were ALN/D5600 administration, seasonal variation, and baseline 25(OH)D. The least squares mean percent change from baseline in serum PTH in the ALN/D5600 group (8.17%) was lower than that in the ALN group (29.98%) (p=0.0091). There was no significant difference between treatment groups in neuromuscular function. Overall safety was similar between groups. In conclusion, the administration of 5600 IU vit-D in the ALN/D5600 group improved vit-D status and reduced the magnitude of PTH increase without significant side-effects after 16 weeks in Korean osteoporotic patients.


Using software to predict occupational hearing loss in the mining industry.
Powerful mining systems typically generate high-level noise that can damage the hearing ability of miners. Engineering noise controls are the most desirable and effective control for overexposure to noise. However, the effects of these noise controls on the actual hearing status of workers are not easily measured. A tool that can provide guidance in assigning workers to jobs based on the noise levels to which they will be exposed is highly desirable. Therefore, the Pittsburgh Mining Research Division (PMRD) of the U.S. National Institute for Occupational Safety and Health (NIOSH) developed a tool to estimate in a systematic way the hearing loss due to occupational noise exposure and to evaluate the effectiveness of developed engineering controls. This computer program is based on the ISO 1999 standard and can be used to estimate the loss of hearing ability caused by occupational noise exposures. In this paper, the functionalities of this software are discussed and several case studies related to mining machinery are presented to demonstrate the functionalities of this software.


Hybrid-DCA: A double asynchronous approach for stochastic dual coordinate ascent.
In prior works, stochastic dual coordinate ascent (SDCA) has been parallelized in a multi-core environment where the cores communicate through shared memory, or in a multi-processor distributed memory environment where the processors communicate through message passing. In this paper, we propose a hybrid SDCA framework for multi-core clusters, the most common high performance computing environment that consists of multiple nodes each having multiple cores and its own shared memory. We distribute data across nodes where each node solves a local problem in an asynchronous parallel fashion on its cores, and then the local updates are aggregated via an asynchronous across-node update scheme. The proposed double asynchronous method converges to a global solution for L-Lipschitz continuous loss functions, and at a linear convergence rate if a smooth convex loss function is used. Extensive empirical comparison has shown that our algorithm scales better than the best known shared-memory methods and runs faster than previous distributed-memory methods. Big datasets, such as one of 280 GB from the LIBSVM repository, cannot be accommodated on a single node and hence cannot be solved by a parallel algorithm. For such a dataset, our hybrid algorithm takes less than 30 seconds to achieve a duality gap of 10-5 on 16 nodes each using 12 cores, which is significantly faster than the best known distributed algorithms, such as CoCoA+, that take more than 160 seconds on 16 nodes.


Shuttle walking test: a new approach for evaluating patients with pacemakers.
To validate an incremental field walking test, the shuttle walking test, as a means of assessing pacing modes and to aid programming of rate responsive pacemakers. Three separate groups of patients were recruited. Reproducibility (n = 10) of the shuttle walking test was assessed by performing three consecutive tests. Comparison of the shuttle walking test with a 10 min walk was assessed in 20 patients. In the third group (n = 10) patients with rate responsive pacemakers were programmed to either VVI fixed rate 70 beats/min or VVIR with the optimal rate response to show the discriminative value of the test. Pacing clinic in a regional cardiothoracic centre. 30 patients with chronotropic competence and dual chamber pacemakers with varying functional capacity and 10 patients with rate responsive pacemakers. Continuous haemodynamic monitoring was obtained using an ambulatory nuclear monitor, the Capintec VEST. Two exercise tests either shuttle walking test or 10 min corridor walk. The shuttle walk is an incremental walking test conducted on a 10 m course where the walking speed is dictated by bleeps on an audio cassette. Reproducibility was demonstrated over three consecutive tests with mean (1 SD) exercise times of 7.6 (1.7) min, 7.7 (1.6), and 7.7 (1.7) min. During the shuttle walk the test patients walked for a mean of 8.3 (1.2) min producing peak relative cardiac outputs of 78 (21) end diastolic volume/min compared with 64.9 (17) end diastolic volume/min for the 10 min walk (P < 0.001); peak heart rates were 118 and 104 beats/min (P < 0.03) respectively. In the third group relative peak cardiac output was significantly greater in VVIR (70 (24) v VVI 52 (15) end diastolic volume/min) (P < 0.009) as were exercise times (VVIR 8.8 (1.3) min v VVI 8.1 (1.3) min) (P < 0.003). The shuttle walk is an easy test to administer, requiring little equipment. It produces a symptom limited maximal performance and will be a useful aid to pacemaker programming as it is reproducible and able to show differences in exercise capacity between pacing modes.


Racial differences in treatment preferences among lupus patients: a two-site study.
To identify the demographic, clinical and psychosocial characteristics associated with racial differences in willingness to receive cyclophosphamide (CYC) or participate in a research clinical trial (RCT) among patients with systemic lupus erythematosus (SLE). Data from 163 African-American (AA) and 180 white (WH) SLE patients were evaluated. Structured interviews and chart reviews were conducted to determine treatment preferences in hypothetical situations and identify variables that may affect preferences. Logistic regression models were performed to evaluate the relationship between patient preferences and race, adjusted for patient characteristics. Among patients who had never received CYC (n=293), 62.9% AAs compared to 87.6% WHs were willing to receive the medication (p<0.001). This difference persisted (OR 0.37 [95% CI, 0.16-0.87]) after adjusting for socio-demographics, clinical characteristics, and perceptions about CYC and physicians. Income and higher perception of CYC effectiveness were other determinants of willingness to receive CYC. Among patients who had never participated in an RCT (n=326), 64.9% AAs compared to 84.3% WHs were willing to do so (p<0.001). This difference persisted (OR 0.41 [95% CI, 0.20-0.83]) after adjusting for socio-demographics, clinical context and patients' perceptions of physicians. SLE damage score, number of immunosuppressive medications and higher trust in physicians were also independently associated with willingness to participate in an RCT. Race remains an independent determinant of treatment preferences after adjustment for income, medications, medication efficacy expectations and trust in physicians. While some factors related to racial differences in preferences are relatively fixed, others that may alleviate these differences also exist, including medication beliefs and provider trust.


The novel protein kinase Vlk is essential for stromal function of mesenchymal cells.
From a list of protein kinases (PKs) that are newly induced upon differentiation of mouse embryonic stem cells to mesendoderm, we identified a previously uncharacterized kinase, Vlk (vertebrate lonesome kinase), that is well conserved in vertebrates but has no homologs outside of the vertebrate lineage. Its kinase domain cannot be classified into any of the previously defined kinase groups or families. Although Vlk is first expressed in E-cadherin-positive anterior visceral endoderm and mesendoderm, its expression is later confined to E-cadherin-negative mesenchyme. Vlk is enriched in the Golgi apparatus and blocks VSVG transport from the Golgi to the plasma membrane. Targeted disruption of Vlk leads to a defect in lung development and to delayed ossification of endochondral bone. Vlk(-/-) mice display neonatal lethality due to respiratory failure, with a suckling defect arising from a cleft palate. Our results demonstrate that Vlk is a novel vertebrate-specific PK that is involved in the regulation of the rate of protein export from the Golgi, thereby playing an important role in the formation of functional stroma by mesenchymal cells.


The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study.
Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Consecutive women undergoing mastectomy ± IBR for breast cancer July-December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients.


Comprehensive follow-up care and life-threatening illnesses among high-risk infants: A randomized controlled trial.
Inner-city high-risk infants often receive limited and fragmented care, a problem that may increase serious illness. To assess whether access to comprehensive care in a follow-up clinic is cost-effective in reducing life-threatening illnesses among high-risk, inner-city infants. Randomized controlled trial. A total of 887 very-low-birth-weight infants born in a Texas county hospital between January 1988 and March 1996 and followed up in a children's hospital clinic. One hundred four infants who became ineligible or died after randomization but before nursery discharge were excluded from the analysis. Infants were randomly assigned to receive routine follow-up care (well-baby care and care for chronic illnesses; n = 441) or comprehensive care (which included the components of routine care plus care for acute illnesses, with 24-hour access to a primary caregiver; n = 446). Life-threatening illnesses (ie, causing death or hospital admission for pediatric intensive care) occurring between nursery discharge and age 1 year, assessed by blinded evaluators from inpatient charts and state Medicaid and vital statistics records; and hospital costs (estimated from department-specific cost-to-charge ratios). Comprehensive care resulted in a mean of 3.1 more clinic visits and 6.7 more telephone conversations with clinic staff (P<.001 for both). One-year outcomes were unknown for fewer comprehensive-care infants than routine-care infants (9 vs 28; P =.001). Identified deaths were similar (11 in comprehensive care vs 13 in routine care; P =.68). The comprehensive-care group had 48% fewer life-threatening illnesses (33 vs 63; P<.001), 57% fewer intensive care admissions (23 vs 53; P =.003), and 42% fewer intensive care days (254 vs 440; P =.003). Comprehensive care did not increase the mean estimated cost per infant for all care ($6265 with comprehensive care and $9913 with routine care). Comprehensive follow-up care by experienced caregivers can be highly effective in reducing life-threatening illness without increasing costs among high-risk inner-city infants. JAMA. 2000;284:2070-2076.


Evaluating the lethal and pre-lethal effects of a range of fungi against adult Anopheles stephensi mosquitoes.
Insecticide resistance is seriously undermining efforts to eliminate malaria. In response, research on alternatives to the use of chemical insecticides against adult mosquito vectors has been increasing. Fungal entomopathogens formulated as biopesticides have received much attention and have shown considerable potential. This research has necessarily focused on relatively few fungal isolates in order to 'prove concept'. Further, most attention has been paid to examining fungal virulence (lethality) and not the other properties of fungal infection that might also contribute to reducing transmission potential. Here, a range of fungal isolates were screened to examine variation in virulence and how this relates to additional pre-lethal reductions in feeding propensity. The Asian malaria vector, Anopheles stephensi was exposed to 17 different isolates of entomopathogenic fungi belonging to species of Beauveria bassiana, Metarhizium anisopliae, Metarhizium acridum and Isaria farinosus. Each isolate was applied to a test substrate at a standard dose rate of 1×109 spores ml-1 and the mosquitoes exposed for six hours. Subsequently the insects were removed to mesh cages where survival was monitored over the next 14 days. During this incubation period the mosquitoes' propensity to feed was assayed for each isolate by offering a feeding stimulant at the side of the cage and recording the number probing. Fungal isolates showed a range of virulence to A. stephensi with some causing >80% mortality within 7 days, while others caused little increase in mortality relative to controls over the study period. Similarly, some isolates had a large impact on feeding propensity, causing >50% pre-lethal reductions in feeding rate, whereas other isolates had very little impact. There was clear correlation between fungal virulence and feeding reduction with virulence explaining nearly 70% of the variation in feeding reduction. However, there were some isolates where either feeding decline was not associated with high virulence, or virulence did not automatically prompt large declines in feeding. These results are discussed in the context of choosing optimum fungal isolates for biopesticide development.


Interactions Between Item Set and Vocoding in Serial Recall.
Serial recall of digits is frequently used to measure short-term memory span in various listening conditions. However, the use of digits may mask the effect of low quality auditory input. Digits have high frequency and are phonologically distinct relative to one another, so they should be easy to identify even with low quality auditory input. In contrast, larger item sets reduce listener ability to strategically constrain their expectations, which should reduce identification accuracy and increase the time and/or cognitive resources needed for identification when auditory quality is low. This diminished accuracy and increased cognitive load should interfere with memory for sequences of items drawn from large sets. The goal of this work was to determine whether this predicted interaction between auditory quality and stimulus set in short-term memory exists, and if so, whether this interaction is associated with processing speed, vocabulary, or attention. We compared immediate serial recall within young adults with normal hearing across unprocessed and vocoded listening conditions for multiple stimulus sets. Stimulus sets were lists of digits (1 to 9), consonant-vowel-consonant (CVC) words (chosen from a list of 60 words), and CVC nonwords (chosen from a list of 50 nonwords). Stimuli were unprocessed or vocoded with an eight-channel noise vocoder. To support interpretation of responses, words and nonwords were selected to minimize inclusion of multiple phonemes from within a confusion cluster. We also measured receptive vocabulary (Peabody Picture Vocabulary Test [PPVT-4]), sustained attention (test of variables of attention [TOVA]), and repetition speed for individual items from each stimulus set under both listening conditions. Vocoding stimuli had no impact on serial recall of digits, but reduced memory span for words and nonwords. This reduction in memory span was attributed to an increase in phonological confusions for nonwords. However, memory span for vocoded word lists remained reduced even after accounting for common phonetic confusions, indicating that lexical status played an additional role across listening conditions. Principal components analysis found two components that explained 84% of the variance in memory span across conditions. Component one had similar load across all conditions, indicating that participants had an underlying memory capacity, which was common to all conditions. Component two was loaded by performance in the vocoded word and nonword conditions, representing the sensitivity of memory span to vocoding of these stimuli. The order in which participants completed listening conditions had a small effect on memory span that could not account for the effect of listening condition. Repetition speed was fastest for digits, slower for words, and slowest for nonwords. On average, vocoding slowed repetition speed for all stimuli, but repetition speed was not predictive of individual memory span. Vocabulary and attention showed no correlation with memory span. Our results replicated previous findings that low quality auditory input can impair short-term memory, and demonstrated that this impairment is sensitive to stimulus set. Using multiple stimulus sets in degraded listening conditions can isolate memory capacity (in digit span) from impaired item identification (in word and nonword span), which may help characterize the relationship between memory and speech recognition in difficult listening conditions.


Noninvasive determination of age-related changes in the human arterial pulse.
Arterial pressure waves were recorded noninvasively from the carotid, radial, femoral, or all three of these arteries of 1,005 normal subjects, aged 2-91 years, using a new transcutaneous tonometer containing a high fidelity Millar micromanometer. Waves were ensemble-averaged into age-decade groups. Characteristic changes were noted with increasing age. In all sites, pulse amplitude increased with advancing age (carotid, 91.3%; radial 67.5%; femoral, 50.1% from first to eighth decade), diastolic decay steepened, and diastolic waves became less prominent. In the carotid pulse, there was, in youth, a second peak on the downstroke of the waves in late systole. After the third decade, this second peak rose with age to merge with and dominate the initial rise. In the radial pulse, a late systolic wave was also apparent, but this occurred later; with age, this second peak rose but not above the initial rise in early systole, even at the eighth decade. In the femoral artery, there was a single systolic wave at all ages. Aging changes in the arterial pulse are explicable on the basis of both an increase in arterial stiffness with increased pulse-wave velocity and progressively earlier wave reflection. These two factors may be separated and effects of the latter measured from pressure wave-contour analysis using an "augmentation index," determined by a computer algorithm developed from invasive pressure and flow data. Changes in peak pressure in the central (carotid) artery show increasing cardiac afterload with increasing age in a normal population; this can account for the cardiac hypertrophy that occurs with advancing age (even as other organs atrophy) and the predisposition to cardiac failure in the elderly. Identification of mechanisms responsible offers a new approach to reduction of left ventricular afterload.


Relationship of cutaneous delayed hypersensitivity to protection from challenge exposure with Salmonella typhimurium in calves.
The purpose of this investigation was to relate cutaneous delayed hypersensitivity reactions to the degree of immunity induced in calves given a live virulent or a modified-live strain of Salmonella typhimurium. Calves were placed into 1 of 5 groups on the basis of the vaccinal strain given and route of the vaccination: (I) nonvaccinated controls, (II) vaccinated twice by IM inoculation with small doses of the live virulent strain, (III) vaccinated (IM) twice with the modified-live strain, (IV) vaccinated (orally) twice with the modified-live strains, and (V) vaccinated (IM, and then orally) twice with the modified-live strain. Skin testing was performed by intradermal injection of fragmented S typhimurium as antigen. Double skin fold thickness and visual assessments were recorded at 3, 6, 24, 48, and 72 hours after antigen was administered. Biopsy samples for histopathologic evaluation were obtained. After vaccination and skin testing were complete, calves were orally challenge exposed with 1.5 X 10(11) virulent S typhimurium. Cutaneous delayed-type hypersensitivity reactions (48 hours) were observed in all except controls (group I) and 2 of 3 calves vaccinated orally with the modified-live vaccine strain (group IV). Significant correlations between positive skin tests and protection from challenge exposure were observed except in group V calves, in which positive skin test results were seen, but adequacy of the immunity (or survival after challenge exposure) was inconsistent.


Functional outcome and muscle wasting in adults with tetanus.
In many countries, in-hospital survival from tetanus is increasing, but long-term outcome is unknown. In high-income settings, critical illness is associated with muscle wasting and poor functional outcome, but there are few data from resource-limited settings. In this study we aimed to assess muscle wasting and long-term functional outcome in adults with tetanus. In a prospective observational study involving 80 adults with tetanus, sequential rectus femoris ultrasound measurements were made at admission, 7 days, 14 days and hospital discharge. Functional outcome was assessed at hospital discharge using the Timed Up and Go test, Clinical Frailty Score, Barthel Index and RAND 36-item Short Form Health Survey (SF-36) and 3 and 6 months after discharge using the SF-36 and Barthel Index. Significant muscle wasting occurred between hospital admission and discharge (p<0.01), particularly in severe disease, where a median 23.49% (interquartile range 10.01-26.07) reduction in rectus femoris cross-sectional area occurred in those with severe (Ablett grades 3 and 4) disease. Muscle mass at discharge was related to objective and subjective measures of physical and emotional function at discharge and 3 and 6 months after discharge. In patients >70 y of age, functional recovery at 6 months was reduced compared with younger patients. Hospital-acquired infection and age were risk factors for muscle wasting. Significant muscle wasting during hospitalization occurred in patients with tetanus, the extent of which correlates with functional outcome.