An audio FIR-DAC in a BCD process for high power Class-D amplifiers

A 322 coefficient semi-digital FIR-DAC using a 1-bit PWM input signal was designed and implemented in a high voltage, audio power bipolar CMOS DMOS (BCD) process. This facilitates digital input signals for an analog class-D amplifier in BCD. The FIR-DAC performance depends on the ISI-resistant nature of this PWM-signal. An impulse response with only positive coefficients was chosen, because of its resistance to deadzone and mismatch. With a DAC current of 0.5 mA, the dynamic range is 111 dB (A-weighted), with SINAD = 103 dB (A-weighted). The current consumption is 1mA for the analog part and 4.8 mA for the digital part. The power consumption is 29 mW at V/sub dd/ = 5 V and the chip area is 2 mm/sup 2/ including the reference diode that can be shared by more channels

The evolution of age-dependent plasticity

When organisms encounter environments that are heterogeneous in time, phenotypic plasticity is often favored by selection. The degree of such plasticity can vary during an organism's lifetime, but the factors promoting differential plastic responses at different ages or life stages remain poorly understood. Here we develop and analyze an evolutionary model to investigate how environmental information is optimally collected and translated into phenotypic adjustments at different ages. We demonstrate that plasticity must often be expected to vary with age in a nonmonotonic fashion. Early in life, it is generally optimal to delay phenotypic adjustments until sufficient information has been collected about the state of the environment to warrant a costly phenotypic adjustment. Toward the end of life, phenotypic adjustments are disfavored as well because their beneficial effects can no longer be fully reaped before death. Our analysis clarifies how patterns of age-dependent plasticity are shaped by the interplay of environmental uncertainty, the accuracy of perceived information, and the costs of phenotypic adjustments with life-history determinants such as the relative strengths of fecundity and viability selection experienced by the organism over its lifetime. We conclude by comparing our results with expectations for alternative mechanisms, including developmental constraints, that promote age-dependent plasticity

Hippocampal Proliferation Is Increased in Presymptomatic Parkinson’s Disease and due to Microglia

Besides dopamine-deficiency related motor symptoms, nonmotor symptoms, including cognitive changes occur in Parkinson's disease (PD) patients, that may relate to accumulation of α-synuclein in the hippocampus (HC). This brain region also contains stem cells that can proliferate. This is a well-regulated process that can, for example, be altered by neurodegenerative conditions. In contrast to proliferation in the substantia nigra and subventricular zone, little is known about the HC in PD. In addition, glial cells contribute to neurodegenerative processes and may proliferate in response to PD pathology. In the present study, we questioned whether microglial cells proliferate in the HC of established PD patients versus control subjects or incidental Lewy body disease (iLBD) cases as a prodromal state of PD. To this end, proliferation was assessed using the immunocytochemical marker minichromosome maintenance protein 2 (MCM2). Colocalization with Iba1 was performed to determine microglial proliferation. MCM2-positive cells were present in the HC of controls and were significantly increased in the presymptomatic iLBD cases, but not in established PD patients. Microglia represented the majority of the proliferating cells in the HC. This suggests an early microglial response to developing PD pathology in the HC and further indicates that neuroinflammatory processes play an important role in the development of PD pathology

Excess direct hospital cost of treating adult patients with ventilator associated respiratory infection (VARI) in Vietnam

INTRODUCTION: Ventilator associated respiratory infections (VARIs) are the most common hospital acquired infections in critical care worldwide. This work aims to estimate the total annual direct hospital cost of treating VARI throughout Vietnam. METHODS: A costing model was constructed to evaluate the excess cost of diagnostics and treatment of VARI in Vietnam. Model inputs included costs for extra lengths of stay, diagnostics, VARI incidence, utilisation of ventilators and antibiotic therapy. RESULTS: With the current VARI incidence rate of 21.7 episodes per 1000 ventilation-days, we estimated 34,428 VARI episodes in the 577 critical care units in Vietnam per year. The extra cost per VARI episode was $1,174.90 and the total annual excess cost was US$40.4 million. A 1% absolute reduction in VARI incidence density would save US$1.86 million annually. For each episode of VARI, the share of excess cost components was 45.1$117 per capita, VARI represents a substantial cost to the health service in Vietnam. Enhanced infection prevention and control and antimicrobial stewardship programmes should be implemented to reduce this

Diagnostic Utility of C4d by Direct Immunofluorescence in Bullous Pemphigoid

ABSTRACT: Bullous pemphigoid (BP) is an autoimmune blistering disease that commonly affects elderly patients. Direct immunofluorescence (DIF) for immunoglobulin G (IgG) and C3c on frozen skin biopsies is the gold standard for the diagnosis of BP. In a minority of cases, IgG and/or C3c are found negative, and in these situations, there is a need for a more stable diagnostic marker of BP. C4d is biologically inactive, but has a long half-life, rendering it a long-lived marker for antibody-mediated complement activation. Previous studies already demonstrated that C4d was diagnostically useful in formalin-fixed paraffin-embedded skin biopsies of patients with BP. We hypothesized that C4d detected by DIF could also be a promising diagnostic marker for BP, particularly in IgG and/or C3c DIF-negative cases. In this single-center retrospective study, 69 cases of BP were analyzed for linear deposition of C4d; of the 69 cases, n = 26 were IgG+/C3c-, n = 10 IgG+/C3c+, and n = 33 IgG-/C3c-. Results were compared with n = 39 negative controls. Seven of the 26 (27%) IgG+/C3c- and 3 of the 33 (9%) IgG-/C3c- BP cases were positive for C4d. All 10 IgG+/C3c+ cases were also C4d positive. In the negative control group, 2 of the 39 (5%) were found positive for C4d. In conclusion, the current study shows that C4d is a more sensitive but not a 100% specific marker of BP. We conclude that C4d by DIF could be an interesting diagnostic adjunct for BP, particularly in IgG-/C3c- double negative cases

Effect of a Fundamental Motor Skills Intervention on Fundamental Motor Skill and Physical Activity in a Preschool Setting: A Cluster Randomized Controlled Trial

Purpose: To determine the effect of a 12-week fundamental motor skill (FMS) program on FMS and physical activity (PA) on preschool-aged children. Method: A cluster randomized controlled trial. The intervention (PhysicaL ActivitY and Fundamental Motor Skills in Pre-schoolers [PLAYFun] Program) was a 12-week games-based program, delivered directly to the children in childcare centers by exercise physiologists. Children in the control arm received the usual preschool curriculum. Outcomes included FMS competence (Test of Gross Motor Development-2) and PA (accelerometer) assessed at baseline, 12 weeks, and 24 weeks (12-wk postintervention). Results: Fifty children (mean age = 4.0 [0.6] y; 54% male) were recruited from 4 childcare centers. Two centers were randomized to PLAYFun and 2 centers were randomized to the waitlist control group. Children attended on average 2.0 (1.0) 40-minute sessions per week. The PLAYFun participants demonstrated significant increases in object control (P < .001) and total FMS (P = .010) competence at week 12, compared with controls in a group × time interaction. Girls, but not boys, in PLAYFun significantly increased moderate to vigorous PA after the intervention (P = .004). These increases were not maintained 12-week postcompletion of PLAYFun. Conclusions: The PLAYFun Program is effective at improving FMS competence in boys and girls and increasing PA in girls. However, improvements are not maintained when opportunities to practice are not sustained

The microbial environment modulates non-genetic maternal effects on egg immunity

BACKGROUND: In a diverse microbial world immune function of animals is essential. Diverse microbial environments may contribute to extensive variation in immunological phenotypes of vertebrates, among and within species and individuals. As maternal effects benefit offspring development and survival, whether females use cues about their microbial environment to prime offspring immune function is unclear. To provide microbial environmental context to maternal effects, we asked if the bacterial diversity of the living environment of female zebra finches Taeniopygia guttata shapes maternal effects on egg immune function. We manipulated environmental bacterial diversity of birds and tested if females increased immunological investment in eggs in an environment with high bacterial diversity (untreated soil) versus low (gamma-sterilized soil). We quantified lysozyme and ovotransferrin in egg albumen and IgY in egg yolk and in female blood, and we used 16S rRNA gene sequencing to profile maternal cloacal and eggshell microbiotas. RESULTS: We found a maternal effect on egg IgY concentration that reflected environmental microbial diversity: females who experienced high diversity deposited more IgY in their eggs, but only if maternal plasma IgY levels were relatively high. We found no effects on lysozyme and ovotransferrin concentrations in albumen. Moreover, we uncovered that variation in egg immune traits could be significantly attributed to differences among females: for IgY concentration in yolk repeatability R = 0.80; for lysozyme concentration in albumen R = 0.27. Furthermore, a partial least squares path model (PLS-PM) linking immune parameters of females and eggs, which included maternal and eggshell microbiota structures and female body condition, recapitulated the treatment-dependent yolk IgY response. The PLS-PM additionally suggested that the microbiota and physical condition of females contributed to shaping maternal effects on egg immune function, and that (non-specific) innate egg immunity was prioritized in the environment with low bacterial diversity. CONCLUSIONS: The microbial environment of birds can shape maternal effects on egg immune function. Since immunological priming of eggs benefits offspring, we highlight that non-genetic maternal effects on yolk IgY levels based on cues from the parental microbial environment may prove important for offspring to thrive in the microbial environment that they are expected to face

Cerebrospinal fluid and blood biomarkers for neurodegenerative dementias: An update of the Consensus of the Task Force on Biological Markers in Psychiatry of the World Federation of Societies of Biological Psychiatry

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