Fabrication of high aspect ratio, non-line-of-sight vias in silicon carbide by a two-photon absorption method.

The future of Moore's Law for high-performance integrated circuits (ICs) is going to be driven more by advanced packaging and three-dimensional (3D) integration than by simply decreasing transistor size. 3D ICs offer low-power consumption, high-performance and a smaller footprint compared to conventional 2D ICs. The key enabling technology to 3D integration is the interposer that provides interconnects to route signals between the chiplets that comprise the IC. However, the fabrication of high-aspect ratio through wafer vias (TWVs), that provide electrical and mechanical connection between chiplets on the top and bottom of the interposer, is one of the important challenges that limit interposer performance. Current fabrication technologies are limited by tapering effects and the need for direct line of sight to the fabrication surface. These limit the possible aspect ratios of vias and require large, complicated surface traces to connect the vias to the chiplets. Here, we demonstrate the fabrication of high-aspect ratio, non-line-of-sight TWVs in silicon carbide (SiC). SiC provides better mechanical, chemical, and thermal performance than silicon (Si). The technique uses an electro-chemical etch process that utilizes two-photon absorption to create any arbitrary 3D structure in SiC allowing for direct, subsurface routing between chiplets.

Acute cannabidiol treatment enhances social interaction in adult male mice.

Cannabidiol (CBD) is a non-intoxicating phytochemical from Cannabis sativa that is increasingly used to manage pain. The potential for CBD to ameliorate dimensional behavior symptoms occurring in multiple psychiatric disorders was suggested, including social interaction impairments. To test this hypothesis, adult male BTBRT+Itpr3tf/J (BTBR) mice, a model of idiopathic autism exhibiting social preference deficits and restrictive repetitive behaviors, were acutely treated with vehicle or 0.1, 1, or 10 mg/kg CBD. Social interaction preference was assessed 50 min after treatment, followed by social novelty preference at 60 min, marble burying at 75 min and social dominance at 120 min. CBD (10 mg/kg) enhanced BTBR social interaction but not social novelty preference, marble burying or dominance, with serum levels = 29 ± 11 ng/mg at 3 h post-injection. Next, acute 10 mg/kg CBD was compared to vehicle treatment in male serotonin transporter (SERT) knock-out mice, since SERT deficiency is an autism risk factor, and in their wildtype background strain controls C57BL/6J mice. CBD treatment generally enhanced social interaction preference and attenuated social novelty preference, yet neither marble burying nor dominance was affected. These findings show acute treatment with as little as 10 mg/kg purified CBD can enhance social interaction preference in male mice that are otherwise socially deficient.

Training Family Medicine Residents to Address the COVID-19 Pandemic: A National Survey of Program Directors.

BACKGROUND AND OBJECTIVES: Public health training became particularly important for family medicine (FM) residency training programs amid the COVID-19 pandemic; the Accreditation Council for Graduate Medical Education (ACGME IV.C.19) requires a structured curriculum in which residents address population health. Our primary goal was to understand if, and to what extent, public health interventions trainings were incorporated into FM residency training programs amid the COVID-19 pandemic. We hypothesized programs with more resources (eg, university affiliates) would be better able to incorporate the training compared to those without such resources (ie, nonuniversity affiliates). METHODS: In 2021, we incorporated items addressing COVID-19 public health training competencies into the 2021 Council of Academic Family Medicine Educational Research Alliance national survey of FM residency program directors. The items addressed the type of training provided, mode of delivery, barriers to providing training, perceived importance of training, and support in delivering training. RESULTS: The overall survey response rate was 46.4% (n=287/619). All programs offered at least some training to residents. There were no statistically significant differences in training intensity between university and nonuniversity affiliates. The length of time an FM residency director spent in their position was positively associated with training intensity (r=0.1430, P=.0252). The biggest barrier to providing the trainings was the need to devote time to other curriculum requirements. CONCLUSIONS: FM residency programs were able to provide some public health interventions training during the pandemic. With increased support and resources, FM resident training curricula may better prepare FM residents now in anticipation of a future pandemic.

Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It?

Autism spectrum disorder (ASD) is a group of complex multifactorial neurodevelopmental disorders characterized by a wide and variable set of neuropsychiatric symptoms, including deficits in social communication, narrow and restricted interests, and repetitive behavior. The immune hypothesis is considered to be a major factor contributing to autism pathogenesis, as well as a way to explain the differences of the clinical phenotypes and comorbidities influencing disease course and severity. Evidence highlights a link between immune dysfunction and behavioral traits in autism from several types of evidence found in both cerebrospinal fluid and peripheral blood and their utility to identify autistic subgroups with specific immunophenotypes; underlying behavioral symptoms are also shown. This review summarizes current insights into immune dysfunction in ASD, with particular reference to the impact of immunological factors related to the maternal influence of autism development; comorbidities influencing autism disease course and severity; and others factors with particular relevance, including obesity. Finally, we described main elements of similarities between immunopathology overlapping neurodevelopmental and neurodegenerative disorders, taking as examples autism and Parkinson Disease, respectively.

Impact of SARS-CoV-2 on neuropsychiatric disorders.

Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019 (COVID-19) from early disease onset. The most frequent symptoms and signs are fatigue, dizziness, impaired consciousness, ageusia, anosmia, radicular pain, and headache, as well as others. Based on the high number of series of cases reported, there is evidence for the implication of the immune system in the pathological mechanism of COVID-19. Although the exact role of the immunological mechanism is not elucidated, two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation. In the context of neurological manifestations associated with COVID-19, neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression, anxiety, mood alterations, psychosis, post-traumatic stress disorder, delirium, and cognitive impairment, which appear to be common in COVID-19 survivors. A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities. We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.

Endocannabinoid System Dysregulation from Acetaminophen Use May Lead to Autism Spectrum Disorder: Could Cannabinoid Treatment Be Efficacious?

Persistent deficits in social communication and interaction, and restricted, repetitive patterns of behavior, interests or activities, are the core items characterizing autism spectrum disorder (ASD). Strong inflammation states have been reported to be associated with ASD. The endocannabinoid system (ECS) may be involved in ASD pathophysiology. This complex network of lipid signaling pathways comprises arachidonic acid and 2-arachidonoyl glycerol-derived compounds, their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. Alterations of the ECS have been reported in both the brain and the immune system of ASD subjects. ASD children show low EC tone as indicated by low blood levels of endocannabinoids. Acetaminophen use has been reported to be associated with an increased risk of ASD. This drug can act through the ECS to produce analgesia. It may be that acetaminophen use in children increases the risk for ASD by interfering with the ECS.This mini-review article summarizes the current knowledge on this topic.

SARS-CoV-2 Infection and Risk Management in Multiple Sclerosis.

The novel coronavirus can cause a severe respiratory disease with impact on the central nervous system, as has been reported by several medical health services. In the COVID-19 pandemic caused by the SARS-CoV-2 neurotrophic virus, neurologists have focused their attention on the early identification of suggestive manifestations of the neurological impact of the disease. In this context, they are exploring related chronic disease and the possibility of achieving a more effective understanding of symptoms derived from COVID-19 infection and those derived from the course of preexisting neurological disease. The present review summarizes evidence from the infection with SARS-CoV-2 and the management of the risks of multiple sclerosis and how it is related to the risks of general comorbidities associated with COVID-19. In addition, we reviewed other factors characteristic of MS, such as relapses, and the maximum tolerated dose of treatment medications from clinical and experimental evidence.

Speech-Stimulating Substances in Autism Spectrum Disorders.

Autism spectrum disorder (ASD) is characterized by the core domains of persistent deficits in social communication and restricted-repetitive patterns of behaviors, interests, or activities. A heterogeneous and complex set of neurodevelopmental conditions are grouped in the spectrum. Pro-inflammatory events and immune system dysfunctions are cellular and molecular events associated with ASD. Several conditions co-occur with ASD: seizures, gastro-intestinal problems, attention deficit, anxiety and depression, and sleep problems. However, language and speech issues are key components of ASD symptoms current therapies find difficult to face. Several speech-stimulating substances have been shown to be effective in increasing speech ability in ASD subjects. The need for large clinical trials to determine safety and efficacy is recommended.

Inflammation and Neuro-Immune Dysregulations in Autism Spectrum Disorders.

Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and interaction and restricted-repetitive patterns of behavior, interests, or activities. Strong inflammation states are associated with ASD. This inflammatory condition is often linked to immune system dysfunction. Several cell types are enrolled to trigger and sustain these processes. Neuro-inflammation and neuro-immune abnormalities have now been established in ASD as key factors in its development and maintenance. In this review, we will explore inflammatory conditions, dysfunctions in neuro-immune cross-talk, and immune system treatments in ASD management.

Optical electric field sensor sensitivity direction rerouting and enhancement using a passive integrated dipole antenna.

This work introduces a passive dipole antenna integrated into the packaging of a slab-coupled optical sensor to enhance the directional sensitivity of electro-optic electric field measurements parallel to the fiber axis. Using the passive integrated dipole antenna described in this work, a sensor that can typically only sense fields transverse to the fiber direction is able to sense a 1.25 kV/m field along the fiber direction with a gain of 17.5. This is verified through simulation and experiment.

Non-perturbing voltage measurement in a coaxial cable with slab-coupled optical sensors.

Voltage in a coaxial cable is measured by an electric-field optical fiber sensor exploiting the proportionality of voltage and electric field in a fixed structure. The sensor is inserted in a hole drilled through the dielectric of the RG-218 coaxial cable and sealed with epoxy to displace all air and prevent the adverse effects of charge buildup during high-voltage measurements. It is shown that the presence of the sensor in the coaxial cable does not significantly increase electrical reflections in the cable. A slab-coupled optical fiber sensor (SCOS) is used for its compact size and dielectric make. The dynamic range of 50 dB is shown experimentally with detection of signals as low as 1 V and up to 157 kV. A low corner of 0.3 Hz is demonstrated and the SCOS is shown to be able to measure 90 ns rise time.

Endocannabinod Signal Dysregulation in Autism Spectrum Disorders: A Correlation Link between Inflammatory State and Neuro-Immune Alterations.

Several studies highlight a key involvement of endocannabinoid (EC) system in autism pathophysiology. The EC system is a complex network of lipid signaling pathways comprised of arachidonic acid-derived compounds (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG), their G-protein-coupled receptors (cannabinoid receptors CB1 and CB2) and the associated enzymes. In addition to autism, the EC system is also involved in several other psychiatric disorders (i.e., anxiety, major depression, bipolar disorder and schizophrenia). This system is a key regulator of metabolic and cellular pathways involved in autism, such as food intake, energy metabolism and immune system control. Early studies in autism animal models have demonstrated alterations in the brain's EC system. Autism is also characterized by immune system dysregulation. This alteration includes differential monocyte and macrophage responses, and abnormal cytokine and T cell levels. EC system dysfunction in a monocyte and macrophagic cellular model of autism has been demonstrated by showing that the mRNA and protein for CB2 receptor and EC enzymes were significantly dysregulated, further indicating the involvement of the EC system in autism-associated immunological disruptions. Taken together, these new findings offer a novel perspective in autism research and indicate that the EC system could represent a novel target option for autism pharmacotherapy.

Slab-coupled optical sensor fabrication using side-polished Panda fibers.

A new device structure used for slab-coupled optical sensor (SCOS) technology was developed to fabricate electric field sensors. This new device structure replaces the D-fiber used in traditional SCOS technology with a side-polished Panda fiber. Unlike the D-fiber SCOS, the Panda fiber SCOS is made from commercially available materials and is simpler to fabricate. The Panda SCOS interfaces easier with lab equipment and exhibits ∼3 dB less loss at link points than the D-fiber SCOS. The optical system for the D-fiber is bandwidth limited by a transimpedance amplifier (TIA) used to amplify to the electric signal. The Panda SCOS exhibits less loss than the D-fiber and, as a result, does not require as high a gain setting on the TIA, which results in an overall higher bandwidth range. Results show that the Panda sensor also achieves comparable sensitivity results to the D-fiber SCOS. Although the Panda SCOS is not as sensitive as other side-polished fiber electric field sensors, it can be fabricated much easier because the fabrication process does not require special alignment techniques, and it is made from commercially available materials.

Acetaminophen Use for Fever in Children Associated with Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restrictive behavior, interests, and activities. Our previous case-control study showed that use of acetaminophen at age 12-18 months is associated with increased likelihood for ASD (OR 8.37, 95% CI 2.08-33.7). In this study, we again show that acetaminophen use is associated with ASD (p = 0.013). Because these children are older than in our first study, the association is reversed; fewer children with ASD vs. non-ASD children use acetaminophen as a "first choice" compared to "never use" (OR 0.165, 95% CI 0.045, 0.599). We found significantly more children with ASD vs. non- ASD children change to the use of ibuprofen when acetaminophen is not effective at reducing fever (p = 0.033) and theorize this change in use is due to endocannabinoid system dysfunction. We also found that children with ASD vs. non-ASD children are significantly more likely to show an increase in sociability when they have a fever (p = 0.037) and theorize that this increase is due to anandamide activation of the endocannabinoid system in ASD children with low endocannabinoid tone from early acetaminophen use. In light of this we recommend that acetaminophen use be reviewed for safety in children.

Split Hopkinson bar measurement using high-speed full-spectrum fiber Bragg grating interrogation.

The development and validation of a high-speed, full-spectrum measurement technique is described for fiber Bragg grating (FBG) sensors. A FBG is surface-mounted to a split-Hopkinson tensile bar specimen to induce high strain rates. The high strain gradients and large strains that indicate material failure are analyzed under high strain rates up to 500 s-1. The FBG is interrogated using a high-speed full-spectrum solid-state interrogator with a repetition rate of 100 kHz. The captured deformed spectra are analyzed for strain gradients using a default interior point algorithm in combination with the modified transfer matrix approach. This paper shows that by using high-speed full-spectrum interrogation of an FBG and the modified transfer matrix method, highly localized strain gradients and discontinuities can be measured without a direct line of sight.

High electric field measurement using slab-coupled optical sensors.

A fiber-optic electric field sensor was developed to measure electric field up to 18 MV/m. The sensor uses resonant coupling between an optical fiber and a nonlinear electro-optical crystal. The sensing system uses high dielectric strength materials to eliminate dielectric breakdown. A postprocessing nonlinear calibration method is developed that maps voltage change to wavelength shift and then converts the wavelength shift to electric field using the transmission spectrum. The nonlinear calibration method is compared against the linear method with electric field pulses having magnitudes from 1.5 to 18 MV/m.

Successful Medical Weight Loss in a Community Setting.

BACKGROUND: Research has shown that meal replacement calorie reduction combined with lifestyle change can more than double the weight loss seen with other diets. However, its widespread acceptance by physicians has been limited, perhaps waiting on evidence that patients are successful in keeping lost weight off. METHODS: Obese patients (108.4 ± 25.7 kg, BMI 38.1 ± 7.9 kg/m2) used a diet of meal replacements combined with weekly classes. While learning about nutrition, exercise, and accountability, patients tracked calorie intake and physical activity. Weight loss and retention rates for rapid weight loss and maintenance phases were measured. Weights then obtained years after treatment ended showed that patients were keeping lost weight off without any ongoing clinic intervention. RESULTS: Records of 714 patients treated in a medical weight loss practice from 2004 through 2012 were reviewed. For all patients, weight loss was 13.6 ± 8.3 kg, and 12.5% of initial weight. The 469 patients who completed 16 weeks of weight loss classes lost 16.7 ± 7.2 kg and 15.1%. 433 patients then enrolled in maintenance classes, and after 12 months had regained only 0.1 ± 9.1 kg and 0.4%. Follow up weights obtained from 173 patients more than 2 years after treatment ended showed persisting weight loss of 14.3 ± 13.7 kg and 12.9%. Final BMI was 32.7 ± 7.7 kg/m2. CONCLUSION: In a medical weight loss program that used meal replacements to reduce calorie intake combined with weekly behavior change classes, weight loss was 16.2 kg and 14.4% for the 61% of all enrollees who completed 16 months of treatment. More importantly, over 2 years later, weight loss of 14.3 kg and 12.9% of initial weight persisted, and patients were not regaining their lost weight.