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The title of the first of three sections in the book, \"Character of Philosophy for Children,\" may be a little misleading if it suggests that its contents will explicate the distinctive qualities or features of philosophy for children. In fact, the section is primarily concerned with \"other\" contemporary ideas and movements which philosophy for children has recently started to explore. The essays include: \"Reasonable Children\" by Michael Pritchard, who claims that young children are capable of reasonableness in the moral domain provided they are capable of empathy, which he believes they are; \"What is the Value of Self - Esteem?\" by San MacColl, who contends that philosophy for children helps them make more realistic self - appraisals; and an engaging if lengthy conversation between John Portelli and Susan Church on \"Whole Language and Philosophy with Children,\" which explores some of the parallels between the two programs and how whole language could benefit by embracing a program of philosophical enquiry with children. Probably Gareth Matthews' \"Thoughts After Piaget\" gives the best glimpse overall of the \"character\" of the movement. He challenges the traditional complaint that philosophy for children is not age - appropriate and provides interesting examples of children's philosophical questions and comments (\"Daddy, why don't I see you double, because I have two eyes and I can see you with each one by itself?\"; p. 72), lending credence to the movement's belief that children are \"naturally\" philosophical. As Portelli points out, however, these natural abilities require nurturing under conditions that are both cognitively rich with philosophical stories and socially democratic in the discussion of ideas.

Although CEACAM1 (CC1) glycoprotein resides at the interface of immune liver injury and metabolic homeostasis, its role in orthotopic liver transplantation (OLT) remains elusive. We aimed to determine whether/how CEACAM1 signaling may affect hepatic ischemia-reperfusion injury (IRI) and OLT outcomes. In the mouse, donor liver CC1 null mutation augmented IRI-OLT (CC1-KO→WT) by enhancing ROS expression and HMGB1 translocation during cold storage, data supported by in vitro studies where hepatic flush from CC1-deficient livers enhanced macrophage activation in bone marrow-derived macrophage cultures. Although hepatic CC1 deficiency augmented cold stress-triggered ASK1/p-p38 upregulation, adjunctive ASK1 inhibition alleviated IRI and improved OLT survival by suppressing p-p38 upregulation, ROS induction, and HMGB1 translocation (CC1-KO→WT), whereas ASK1 silencing (siRNA) promoted cytoprotection in cold-stressed and damage-prone CC1-deficient hepatocyte cultures. Consistent with mouse data, CEACAM1 expression in 60 human donor liver biopsies correlated negatively with activation of the ASK1/p-p38 axis, whereas low CC1 levels associated with increased ROS and HMGB1 translocation, enhanced innate and adaptive immune responses, and inferior early OLT function. Notably, reduced donor liver CEACAM1 expression was identified as one of the independent predictors for early allograft dysfunction (EAD) in human OLT patients. Thus, as a checkpoint regulator of IR stress and sterile inflammation, CEACAM1 may be considered as a denominator of donor hepatic tissue quality, and a target for therapeutic modulation in OLT recipients.

Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type MB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn-/-mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing and/or sequencing capacity, which can also introduce biases 1 – 3 . SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing 4 , 5 . Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

BackgroundUncontrolled hypertension contributes to disparities in cardiovascular outcomes. Patient intervention strategies informed by behavioral economics and social psychology could improve blood pressure (BP) control in disadvantaged minority populations.ObjectiveTo assess the impact on BP control of an intervention combining short-term financial incentives with promotion of intrinsic motivation among highly disadvantaged patients.DesignRandomized controlled trial.ParticipantsTwo hundred seven adults (98% African American or Latino) aged 18 or older with uncontrolled hypertension attending Federally Qualified Health Centers.InterventionSix-month intervention, combining financial incentives for measuring home BP, recording medication use, BP improvement, and achieving target BP values with counseling linking hypertension control efforts to participants’ personal reasons to stay healthy.Main MeasuresPrimary outcomes: percentage achieving systolic BP (SBP) < 140 mmHg, percentage achieving diastolic BP (DBP) < 90 mmHg, and changes in SBP and DBP, all after 6 months. Priority secondary outcomes were SBP < 140 mmHg, DBP < 90 mmHg, and BP change at 12 months, 6 months after the intervention ended.Key ResultsAfter 6 months, rates of achieving target BP values for intervention and control subjects respectively was 57.1% vs. 40.2% for SBP < 140 mmHg (adjusted odds ratio (AOR) 2.53 (1.13–5.70)), 79.8% vs 70.1% for DBP < 90 mmHg (AOR 2.50 (0.84–7.44)), and 53.6% vs 40.2% for achieving both targets (AOR 2.04 (0.92–4.52)). However, at 12 months, the groups did not differ significantly in these 3 measures: 39.5% vs 35.0% for SBP (AOR 1.20 (0.51–2.83)), 68.4% vs 75.0% for DBP (AOR 0.70 (0.24–2.09)), and 35.5% vs 33.8% for both (AOR 1.03 (0.44–2.42)). Change in absolute SBP and DBP did not differ significantly between the groups at 6 or 12 months. Exploratory post hoc analysis revealed intervention benefit only occurred among individuals whose providers intensified their regimens, but not among those with intensification but no intervention.ConclusionsThe intervention achieved short-term improvement in SBP control in a highly disadvantaged population. Despite attempts to enhance intrinsic motivation, the effect was not sustained after incentives were withdrawn. Future research should evaluate combined patient/provider strategies to enhance such interventions and sustain their benefit.Trial RegistrationNCT01402453; http://clinicaltrials.gov/show/NCT01402453

Silicon carbide (SiC) power metal-oxide-semiconductor field effect transistors (MOSFETs) are space-ready in terms of typical reliability measures. However, single event burnout (SEB) due to heavy-ion irradiation often occurs at voltages 50% or lower than specified breakdown. Failure rates in space are estimated for burnout of 1200 V devices based on the experimental data for burnout and the expected heavy-ion linear energy transfer (LET) spectrum in space.

Wireless neural stimulators are being developed to address problems associated with traditional lead-based implants. However, designing wireless stimulators on the sub-millimeter scale (<1 mm ) is challenging. As device size shrinks, it becomes difficult to deliver sufficient wireless power to operate the device. Here, we present a sub-millimeter, inductively powered neural stimulator consisting only of a coil to receive power, a capacitor to tune the resonant frequency of the receiver, and a diode to rectify the radio-frequency signal to produce neural excitation. By replacing any complex receiver circuitry with a simple rectifier, we have reduced the required voltage levels that are needed to operate the device from 0.5 to 1 V (e.g., for CMOS) to ~0.25-0.5 V. This reduced voltage allows the use of smaller receive antennas for power, resulting in a device volume of 0.3-0.5 mm . The device was encapsulated in epoxy, and successfully passed accelerated lifetime tests in 80°C saline for 2 weeks. We demonstrate a basic proof-of-concept using stimulation with tens of microamps of current delivered to the sciatic nerve in rat to produce a motor response.

Cardiovascular disease, including aortic root dilation, dissection, and rupture, is the leading cause of mortality in patients with Marfan syndrome (MFS). The maximal aortic root diameter at the sinuses of Valsalva is considered the best predictor of adverse cardiovascular outcome. Although advances in therapy have improved life expectancy, affected individuals continue to suffer cardiovascular morbidity and mortality. Recent studies in an FBN1-targeted mouse model of MFS with aortic disease similar to that seen in humans showed that treatment with losartan normalized aortic root growth and aortic wall architecture. The Pediatric Heart Network designed a randomized clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in subjects with MFS receiving atenolol or losartan. Individuals 6 months to 25 years of age with a body surface area–adjusted aortic root z score >3.0 will be eligible for inclusion. The primary aim is to compare the effect of atenolol therapy with that of losartan therapy on the rate of aortic root growth over 3 years. Secondary end points include progression of aortic regurgitation; incidence of aortic dissection, aortic root surgery, and death; progression of mitral regurgitation; left ventricular size and function; echocardiographically derived measures of central aortic stiffness; skeletal and somatic growth; and incidence of adverse drug reactions. This randomized trial should make a substantial contribution to the management of individuals with MFS and expand our understanding of the mechanisms responsible for the aortic manifestations of this disorder.