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Archaeologists tend to produce slow data that is contextually rich but often difficult to generalize. An example is the analysis of lithic microdebitage, or knapping debris, that is smaller than 6.3 mm (0.25 in.). So far, scholars have relied on manual approaches that are prone to intra- and interobserver errors. In the following, we present a machine learning–based alternative together with experimental archaeology and dynamic image analysis. We use a dynamic image particle analyzer to measure each particle in experimentally produced lithic microdebitage (N = 5,299) as well as an archaeological soil sample (N = 73,313). We have developed four machine learning models based on Naïve Bayes, glmnet (generalized linear regression), random forest, and XGBoost (“Extreme Gradient Boost[ing]”) algorithms. Hyperparameter tuning optimized each model. A random forest model performed best with a sensitivity of 83.5%. It misclassified only 28 or 0.9% of lithic microdebitage. XGBoost models reached a sensitivity of 67.3%, whereas Naïve Bayes and glmnet models stayed below 50%. Except for glmnet models, transparency proved to be the most critical variable to distinguish microdebitage. Our approach objectifies and standardizes microdebitage analysis. Machine learning allows studying much larger sample sizes. Algorithms differ, though, and a random forest model offers the best performance so far.

The growth in virtual work is reshaping how leaders interface with their followers: Face-to-face interactions are increasingly being supplanted by virtual exchanges. To advance understanding of the implications of leading in this changing environment, we apply functional leadership theory to synthesize the findings of the virtual leadership research that has been conducted across different leadership perspectives and levels of analysis. We identify four traditional leadership functions that empirical research suggests have a stronger effect on follower need satisfaction in virtual settings and highlight a new function—facilitate the use of technology—as particularly germane to virtual leadership. Our review reveals several promising future research directions, including the need to examine the effects of leadership along the full spectrum of virtuality and to consider the unique challenges that leaders may encounter in hybrid work environments. We also outline important practical implications for organizations, leaders, and their followers.

Recent interest in measuring methane (CH4) emissions from abandoned oil and gas infrastructure has resulted in several methods being continually used to quantify point source emissions less than 200 g CH4 h−1. The choice of measurement approach depends on how close observers can come to the source, the instruments available, and the meteorological/micrometeorological conditions. As such, static chambers, dynamic chambers, Bacharach Hi Flow Sampler (BHFS) measurements, Gaussian plume (GP) modeling, and backward Lagrangian stochastic (bLs) models have all been used, but there is no clear understanding of the accuracy or precision of each method. To address this, we copy the experimental design for each of the measurement methods to make single field measurements of a known source, to simulate single measurement field protocol, and then make repeat measurements to generate an understanding of the accuracy and precision of each method. Here, we present estimates for the average percentage difference between the measured emission and the known emission for three repeat measurements, Ar, for emissions of 40 to 200 g CH4 h−1. The static chamber data were not presented because of safety concerns during the experiments. Both the dynamic chamber (Ar = −10 %, −8 %, and −10 % at emission rates of 40, 100, and 200 g CH4 h−1, respectively) and BHFS (Ar = −18 %, −16 %, and −18 %) repeatedly underestimate the emissions, but the dynamic chamber had better accuracy. The standard deviation of emissions from these direct measurement methods remained relatively constant for emissions between 40 and 200 g CH4 h−1. For the far-field methods, the bLs method generally underestimated emissions (Ar = +6 %, −6 %, and −7 %) while the GP method significantly overestimated the emissions (Ar = +86 %, +57 %, and +29 %) despite using the same meteorological and concentration data as input. Variability in wind speed, wind direction, and atmospheric stability over the 20 min averaging period are likely to propagate through to large variability in the emission estimate, making these methods less precise than the direct measurement methods. To our knowledge, this is the first time that methods for measuring CH4 emissions from point sources between 40 and 200 g CH4 h−1 have been quantitatively assessed against a known reference source and against each other.

The U.S. military requires medical readiness to support forward-deployed combat operations. Because time and distance to neurosurgical capabilities vary within the deployed trauma system, nonneurosurgeons are required to perform emergent cranial procedures in select cases. It is unclear whether these surgeons have sufficient training in these procedures.This quality-improvement study involved a voluntary, anonymized specialty-specific survey of active-duty surgeons about their experience and attitudes toward U.S. military emergency neurosurgical training.Survey responses were received from 104 general surgeons and 26 neurosurgeons. Among general surgeons, 81% have deployed and 53% received training in emergency neurosurgical procedures before deployment. Only 16% of general surgeons reported participating in craniotomy/craniectomy procedures in the last year. Nine general surgeons reported performing an emergency neurosurgical procedure while on deployment/humanitarian mission, and 87% of respondents expressed interest in further predeployment emergency neurosurgery training. Among neurosurgeons, 81% had participated in training nonneurosurgeons and 73% believe that more comprehensive training for nonneurosurgeons before deployment is needed. General surgeons proposed lower procedure minimums for competency for external ventricular drain placement and craniotomy/craniectomy than did neurosurgeons. Only 37% of general surgeons had used mixed/augmented reality in any capacity previously; for combat procedures, most (90%) would prefer using synchronous supervision via high-fidelity video teleconferencing over mixed reality.These survey results show a gap in readiness for neurosurgical procedures for forward-deployed general surgeons. Capitalizing on capabilities such as mixed/augmented reality would be a force multiplier and a potential means of improving neurosurgical capabilities in the forward-deployed environments.

Principles for determining physician compensation in the provision of virtual care are discussed along with analysis of the virtual care components included in the 2022 Ontario Physician Services Agreement (SEAMO 2022). Ministries and medical associations should continue to discuss appropriate payment for virtual advice for patients who do not have a primary care provider. They should also determine methods for payment for physician engagement in apps designed to optimize treatment of chronic diseases.

Background Blood pressure (BP) is often inadequately controlled in children treated for hypertension, and personalized (n-of-1) trials show promise for tailoring treatment choices. We assessed whether patients whose treatment choices are informed by an n-of-1 trial have improved BP control compared to usual care. Methods A randomized clinical trial was conducted in a pediatric hypertension clinic in Houston from April 2018 to September 2020. Hypertensive adolescents and young adults 10–22 years old were randomized 1:1 to a strategy of n-of-1 trial using ambulatory BP monitoring to inform treatment choice or usual care, with treatment selected by physician preference. The primary outcome was the proportion of patients with ambulatory BP control at 6 months in a Bayesian analysis. Results Among 49 participants (23 randomized to n-of-1 trials and 26 to usual care), mean age was 15.6 years. Using skeptical priors, we found a 69% probability that n-of-1 trials increased BP control at 6 months (Bayesian odds ratio (OR) 1.24 (95% credible interval (CrI) 0.51, 2.97), and 74% probability using neutral informed priors (OR 1.45 (95% CrI 0.48, 4.53)). Systolic BP was reduced in both groups, with a 93% probability of greater reduction in the n-of-1 trial group (mean difference between groups = −3.6 mm Hg (95% CrI −8.3, 1.28). There was no significant difference in side effect experience or caregiver satisfaction. Conclusions Among hypertensive adolescents and young adults, n-of-1 trials with ambulatory BP monitoring likely increased the probability of BP control. A large trial is needed to assess their use in clinical practice. ClinicalTrials.gov NCT03461003 Clinical trial registry ClinicalTrials.gov; NCT 03461003

The COVID-19 pandemic has caused unprecedented health care challenges mandating surgical service reconfiguration. Within our hospital, emergency and elective streams were separated and self-contained Protected Elective Surgical Units were developed to mitigate against infection-related morbidity. Aims of this study were to determine the risk of COVID-19 transmission and mortality and whether the development of Protected Elective Surgical Units can result in significant reduction in risk.A retrospective observational study of consecutive patients from 18 specialties undergoing elective or emergency surgery under general, spinal, or epidural anaesthetic over a 12-month study period was undertaken. Primary outcome measures were 30-day postoperative COVID-19 transmission rate and mortality. Secondary adjusted analyses were performed to ascertain hospital and Protected Elective Surgical Unit transmission rates.Between 15 March 2020 and 14 March 2021, 9,925 patients underwent surgery: 6,464 (65.1%) elective, 5,116 (51.5%) female, and median age 57 (39-70). A total of 69.5% of all procedures were performed in Protected Elective Surgical Units. Overall, 30-day postoperative COVID-19 transmission was 2.8% (3.4% emergency vs 1.2% elective P .001). Protected Elective Surgical Unit postoperative transmission was significantly lower than non-Protected Elective Surgical Unit (0.42% vs 3.2% P .001), with an adjusted likely in-hospital Protected Elective Surgical Unit transmission of 0.04%. The 30-day all-cause mortality was 1.7% and was 14.6% in COVID-19-positive patients. COVID-19 infection, age 70, male sex, American Society of Anesthesiologists grade 2, and emergency surgery were all independently associated with mortality.This study has demonstrated that Protected Elective Surgical Units can facilitate high-volume elective surgical services throughout peaks of the COVID-19 pandemic while minimising viral transmission and mortality. However, mortality risk associated with perioperative COVID-19 infection remains high.

After three “lost” years, the 50th International Symposium on High Performance Liquid Phase Separations and Related Techniques, or HPLC 2022, returned. The symposium was held at the Town and Country Hotel and Conference Center in sunny San Diego, California, from June 18–23, 2022. The HPLC symposium continues to be the premier event bringing together leading scientists in the field of liquid chromatography (LC) and related techniques. The conference was chaired by Frantisek Svec of Charles University, and, especially under the uncertain times leading up to the event, was very successful and welcomed by the attendees.

As a brief, noninvasive, cost-effective, and technology-driven therapy, biofeedback is a promising and welcomed clinical intervention for children and adolescents with pediatric chronic pain conditions. The aim of this pilot study was to explore the application of a brief Heart Rate Variability (HRV) biofeedback intervention supplemented by at-home breathing practice as a tool for reducing symptomatology associated with chronic pain in a pediatric urban hospital setting.Twenty-one participants aged 10-17 years (M = 14.05, SD = 1.91; 76% female) and their caregivers completed the study. Participants were randomized to either 1) receive immediate biofeedback treatment including at-home breathing practice or 2) to be placed on a 4-week waitlist and then enrolled in the biofeedback treatment. Study outcomes included self-reported pain intensity, health-related quality of life (HRQOL), and anxiety sensitivity. HRV data were obtained from biofeedback sessions.Following biofeedback treatment, participants achieved significant reductions in self-reported pain intensity, higher levels of self-reported school functioning, and increased HRV, as measured by Blood Volume Pulse (BVP) amplitude. Participants in the waitlist group experienced an increase in pain intensity during the waitlist period.Further research is needed to understand the mechanisms underlying HRV biofeedback and its treatment of pediatric chronic pain.Nurses are ideal practitioners for biofeedback given their training in physiology and background in healthcare and should be encouraged to explore training in this area. Suggested biofeedback-related apps and mobile devices to share with patients at bedside are provided.

Lipid-lowering therapy with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition are effective strategies in reducing cardiovascular disease risk; however, concerns remain about potential long-term adverse neurocognitive effects.This genetics-based study aimed to evaluate the relationships of long-term PCSK9 inhibition and statin use on neurocognitive outcomes.We extracted single-nucleotide polymorphisms in 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) and PCSK9 from predominantly European ancestry-based genome-wide association studies summary-level statistics of low-density lipoprotein cholesterol and performed drug-target Mendelian randomization, proxying the potential neurocognitive impact of drug-based PCSK9 and HMGCR inhibition using a range of outcomes to capture the complex facets of cognition and dementia.Using data from a combined sample of ∼740,000 participants, we observed a neutral cognitive profile related to genetic PCSK9 inhibition, with no significant effects on cognitive performance, memory performance, or cortical surface area. Conversely, we observed several adverse associations for HMGCR inhibition with lowered cognitive performance (beta: -0.082; 95% CI: -0.16 to -0.0080; P = 0.03), reaction time (beta = 0.00064; 95% CI: 0.00030-0.00098; P = 0.0002), and cortical surface area (beta = -0.18; 95% CI: -0.35 to -0.014; P = 0.03). Neither PCSK9 nor HMGCR inhibition impacted biomarkers of Alzheimer's disease progression or Lewy body dementia risk. Consistency of findings across Mendelian randomization methods accommodating different assumptions about genetic pleiotropy strengthens causal inference.Using a wide range of cognitive function and dementia endpoints, we failed to find genetic evidence of an adverse PCSK9-related impact, suggesting a neutral cognitive profile. In contrast, we observed adverse neurocognitive effects related to HMGCR inhibition, which may well be outweighed by the cardiovascular benefits of statin use, but nonetheless may warrant pharmacovigilance.

Objectives Reduction in unnecessary services is one strategy for increasing the value of health care. Reference laboratory, or send-out, tests are associated with considerable costs. We investigated whether displaying cost and turnaround time (TAT), or time-to-result, for reference laboratory tests at the time of order entry in the electronic health record (EHR) system would impact provider ordering practices. Methods Reference laboratory test cost and TAT data were randomized prior to the study and only displayed for the intervention group. A 24-month dataset composed of 12 months each for baseline and study periods was extracted from the clinical data mart. A difference-in-differences (DID) analysis was conducted using a linear mixed-effects model to estimate the association between the intervention and changes in test-ordering patterns. Results In the inpatient setting, the DIDs of aggregate test-order costs and volume were not different among the control and intervention groups (p = 0.31 and p = 0.26, respectively). In the ambulatory setting, the DIDs of aggregate test-order costs and volume were not different among the control and intervention groups (p = 0.82 and p = 0.51, respectively). For both inpatient and ambulatory settings, no significant difference was observed in the DID of aggregate test-order costs and volumes calculated in respect to stratified relative cost and TAT groups (p > 0.05). Conclusion Lack of alternative tests, test orders placed at a late step in patient management, and orders facilitated by trainees or mid-level providers may have limited the efficacy of the intervention. Our randomized study demonstrated no significant association between the display of cost or TAT display and ordering frequency.

Delayed atomic layer deposition (ALD) of ZnO, i.e., area selective (AS)-ALD, was successfully achieved on silicon wafers (SiSiO2) terminated with tris(dimethylamino)methylsilane (TDMAMS). This resist molecule was deposited in a home-built, near-atmospheric pressure, flow-through, gas-phase reactor. TDMAMS had previously been shown to react with SiSiO2 in a single cycle/reaction and to drastically reduce the number of silanols that remain at the surface. ZnO was deposited in a commercial ALD system using dimethylzinc (DMZ) as the zinc precursor and H2O as the coreactant. Deposition of TDMAMS was confirmed by spectroscopic ellipsometry (SE), X-ray photoelectron spectroscopy (XPS), and wetting. ALD of ZnO, including its selectivity on TDMAMS-terminated SiSiO2 (SiSiO2TDMAMS), was confirmed by in situ multi-wavelength ellipsometry, ex situ SE, XPS, and/or high-sensitivity/low-energy ion scattering (HS-LEIS). The thermal stability of the TDMAMS resist layer, which is an important parameter for AS-ALD, was investigated by heating SiSiO2TDMAMS in air and nitrogen at 330 °C. ALD of ZnO takes place more readily on SiSiO2TDMAMS heated in the air than in N2, suggesting greater damage to the surface heated in the air. To better understand the in situ ALD of ZnO on SiSiO2TDMAMS and modified (thermally stressed) forms of it, the ellipsometry results were plotted as the normalized growth per cycle. Even one short pulse of TDMAMS effectively passivates SiSiO2. TDMAMS can be a useful, small-molecule inhibitor of ALD of ZnO on SiSiO2 surfaces.

Delayed atomic layer deposition (ALD) of ZnO, i.e., area selective (AS)-ALD, was successfully achieved on silicon wafers (Si/SiO2) terminated with tris(dimethylamino)methylsilane (TDMAMS). This resist molecule was deposited in a home-built, near atmospheric pressure, flow-through , gas-phase reactor. TDMAMS has been shown to react with Si/SiO2 in a single cycle/reaction and to drastically reduce the number of silanols that remain at the surface. ZnO was deposited in a commercial ALD system using dimethylzinc (DMZ) as the zinc precursor and H2O as the coreactant. Deposition of TDMAMS was confirmed by spectroscopic ellipsometry (SE), X-ray photoelectron spectroscopy (XPS), and wetting. ALD of ZnO, including its selectivity on TDMAMS – terminated Si/SiO2 (Si/SiO2/TDMAMS), was confirmed by in situ ellipsometry, ex situ SE, XPS, and/or high sensitivity – low energy ion scattering (HS-LEIS). The thermal stability of the TDMAMS resist layer, which is an important parameter for AS-ALD, was investigated by heating Si/SiO2/TDMAMS in air and nitrogen at 330 ºC. ALD of ZnO takes place more readily on Si/SiO2/TDMAMS heated in the air than in N2, suggesting greater damage to the surface heated in the air. To better understand the in situ ALD of ZnO, the data were also plotted as the normalized growth per cycle and to show the selectivity. Even one, short pulse of TDMAMS effectively passivates Si/SiO2. TDMAMS can be an effective small molecule inhibitor of ALD of ZnO on Si/SiO2 surfaces.

Contains fulltext : 283431.pdf (Publisher’s version ) (Closed access) Aberrations in nuclear size and shape are commonly used to identify cancerous tissue. However, it remains unclear whether the disturbed nuclear structure directly contributes to the cancer pathology or is merely a consequence of other events occurring during tumorigenesis. Here, we show that highly invasive and proliferative breast cancer cells frequently exhibit Akt-driven lower expression of the nuclear envelope proteins lamin A/C, leading to increased nuclear deformability that permits enhanced cell migration through confined environments that mimic interstitial spaces encountered during metastasis. Importantly, increasing lamin A/C expression in highly invasive breast cancer cells reflected gene expression changes characteristic of human breast tumors with higher LMNA expression, and specifically affected pathways related to cell-ECM interactions, cell metabolism, and PI3K/Akt signaling. Further supporting an important role of lamins in breast cancer metastasis, analysis of lamin levels in human breast tumors revealed a significant association between lower lamin A levels, Akt signaling, and decreased disease-free survival. These findings suggest that downregulation of lamin A/C in breast cancer cells may influence both cellular physical properties and biochemical signaling to promote metastatic progression.

The use of drones fo r geophysical data acquisition and artificial intelligence (AI) for geophysical data processing, imaging, and interpretation are active focus areas in current industry and academic applications. Unlocking their cumulative potential in single-focus applications can have a transformative impact, possibly leading to dramatic cost reductions in key use cases and new application areas for enhanced actionable business intelligence. We present field study results from Texas and California that show the potential for imaging pipelines and other subsurface infrastructure by using AI-based methods on high-resolution aboveground magnetic data. The superior resolution and interpretability over conventional geophysical inversion is demonstrated. The method has the potential to provide actionable intelligence in several business-use cases for detecting and characterizing pipelines, crossing zones for multiple pipes, etc. at dramatically reduced costs. The advanced algorithms and workflows used resulted in a 100-fold increase in efficiency and delivered results in two days compared to what could take several months using generally available open-source deep learning AI workflows and software. Future direction of development is to validate against excavation-/drill-bit-/inline-tool-based ground truth and further extend and develop this process to deliver near real-time results. The techniques used are general and can be applied to other geophysical data including seismic, electromagnetic, and gravity at various scales and resolution.

This article covers liquid chromatography (LC) columns and accessories commercially released after Pittcon 2021 through this year’s virtual conference. Like in the past, LCGC sent out a survey in late 2021 and early 2022 asking vendors to supply information on products launched over the past year. Note that new products for gas chromatography (GC), LC instrumentation and software, and sample preparation are covered elsewhere. The information for this article was obtained over several months; therefore, it is possible that some information was missed or misinterpreted. The reader is encouraged to check with specific vendor sites for additional products as well as more detailed information on product usage and attributes. Links to vendor sites are provided where applicable.

Single crystals of Al-free, ferromagnesian jeffbenite up to 200 µm in size have been synthesized at 15 GPa and 1200 °C in a 1200 tonne multi-anvil press from a starting composition in the forsteritefayalite-magnetite-water system. This phase has the approximate formula Mg2.62Fe0.872+Fe1.633+Si2.88O12 and is observed to coexist with a Ca-free clinopyroxene plus what appears to be quenched melt. The crystal structure has been refined from single-crystal X-ray diffraction data and is similar to that determined for natural Al-bearing jeffbenite, Mg3Al2Si3O12, reported from inclusions in superdeep diamonds. The structure is a tetragonal orthosilicate in space group I42d with a = 6.6449(4) Å, c = 18.4823(14) Å, and is structurally more closely related to zircon than to garnet. The T2 site is larger than T1, shares an edge with the M2 octahedron, and incorporates significant Fe3+. Because of the tetrahedral incorporation of trivalent cations, jeffbenite appears to be compositionally distinct from garnet. Previous speculations that the phase may only occur as a retrograde decompression product from bridgmanite are not supported by its direct synthesis under transition zone conditions. The phase has a calculated density of 3.93 g/cm3, which is indistinguishable from a garnet of comparable composition, and is a possible component in the mantle transition zone under oxidizing conditions or with Al-rich compositions.

Roll-to-roll (R2R) slot-die coating of polymer electrolyte membrane fuel cell (PEMFC) catalyst layers represents a scalable deposition method for producing 10-20 m2·min-1 of catalyst-coated gas diffusion layers (GDLs). This high-throughput production technique will help lower the cost of PEMFC catalyst layers. The uniformity of the wet layer applied by slot die deposition is affected by process parameters such as substrate speed, vacuum pressure applied at the upstream meniscus, gap between the slot die lips and substrate, ink rheology, and other ink and substrate properties. The set of conditions for producing a defect-free coating with a dilute ink typically requires little to no upstream vacuum pressure, so suitable operating conditions can be found easily through trial and error and operator intuition. However, the higher viscosity of more concentrated inks dramatically shifts the range of settings that result in a homogeneous coating to higher vacuum levels, which are harder to find through hit or miss. A predictive model showing the range of operable conditions decreases material wastage inherent in experimentally searching for suitable parameters. In this study, the defect-free coating parameter window is explored experimentally and theoretically for two concentrations of PEFC cathode inks. Both a full capillary hydrodynamic model and a computationally cheaper viscocapillary model successfully predict the experimentally determined coating window within the experimental and model uncertainty limits for inks with 5.3 wt.% and 12.0 wt.% solids ink while maintaining the 0.1 mgPt·cm-2 Pt areal loading target. This paper demonstrates a viable pathway for meeting the $30/kWnet ultimate cost target of the United States Department of Energy (U.S. DOE) Hydrogen Fuel Cells Technologies Office (HFTO). The concentrated ink lowers the thermal energy and capital expenditure (CapEx) budget of the coating process by decreasing the amount of time, energy, and floorspace required for drying the coating.

Biological aging is accompanied by increasing morbidity, mortality, and healthcare costs; however, its molecular mechanisms are poorly understood. Here, we use multi-omic methods to integrate genomic, transcriptomic, and metabolomic data and identify biological associations with four measures of epigenetic age acceleration and a human longevity phenotype comprising healthspan, lifespan, and exceptional longevity (multivariate longevity). Using transcriptomic imputation, fine-mapping, and conditional analysis, we identify 22 high confidence associations with epigenetic age acceleration and seven with multivariate longevity. FLOT1, KPNA4, and TMX2 are novel, high confidence genes associated with epigenetic age acceleration. In parallel, cis-instrument Mendelian randomization of the druggable genome associates TPMT and NHLRC1 with epigenetic aging, supporting transcriptomic imputation findings. Metabolomics Mendelian randomization identifies a negative effect of non-high-density lipoprotein cholesterol and associated lipoproteins on multivariate longevity, but not epigenetic age acceleration. Finally, cell-type enrichment analysis implicates immune cells and precursors in epigenetic age acceleration and, more modestly, multivariate longevity. Follow-up Mendelian randomization of immune cell traits suggests lymphocyte subpopulations and lymphocytic surface molecules affect multivariate longevity and epigenetic age acceleration. Our results highlight druggable targets and biological pathways involved in aging and facilitate multi-omic comparisons of epigenetic clocks and human longevity.

Non-invasive brain stimulation is designed to target accessible brain regions that underlie many psychiatric disorders. One such method, transcranial magnetic stimulation (TMS), is commonly used in patients with treatment-resistant depression (TRD). However, for non-responders, the choice of an alternative therapy is unclear and often decided empirically without detailed knowledge of precise circuit dysfunction. This is also true of invasive therapies, such as deep brain stimulation (DBS), in which responses in TRD patients are linked to circuit activity that varies in each individual. If the functional networks affected by these approaches were better understood, a theoretical basis for selection of interventions could be developed to guide psychiatric treatment pathways. The mechanistic understanding of TMS is that it promotes long-term potentiation of cortical targets, such as dorsolateral prefrontal cortex (DLPFC), which are attenuated in depression. DLPFC is highly interconnected with other networks related to mood and cognition, thus TMS likely alters activity remote from DLPFC, such as in the central executive, salience and default mode networks. When deeper structures such as subcallosal cingulate cortex (SCC) are targeted using DBS for TRD, response efficacy has depended on proximity to white matter pathways that similarly engage emotion regulation and reward. Many have begun to question whether these networks, targeted by different modalities, overlap or are, in fact, the same. A major goal of current functional and structural imaging in patients with TRD is to elucidate neuromodulatory effects on the aforementioned networks so that treatment of intractable psychiatric conditions may become more predictable and targeted using the optimal technique with fewer iterations. Here, we describe several therapeutic approaches to TRD and review clinical studies of functional imaging and tractography that identify the diverse loci of modulation. We discuss differentiating factors associated with responders and non-responders to these stimulation modalities, with a focus on mechanisms of action for non-invasive and intracranial stimulation modalities. We advance the hypothesis that non-invasive and invasive neuromodulation approaches for TRD are likely impacting shared networks and critical nodes important for alleviating symptoms associated with this disorder. We close by describing a therapeutic framework that leverages personalized connectome-guided target identification for a stepwise neuromodulation paradigm.

Thyroid hormone (TH) action controls brain development in a spatiotemporal manner. Previously, we demonstrated that perinatal hypothyroidism led to formation of a periventricular heterotopia in developing rats. This heterotopia occurs in the posterior telencephalon, and its formation was preceded by loss of radial glia cell polarity. As radial glia mediate cell migration and originate in a progenitor cell niche called the ventricular zone (VZ), we hypothesized that TH action may control cell signaling in this region. Here we addressed this hypothesis by employing laser capture microdissection and RNA-Seq to evaluate the VZ during a known period of TH sensitivity. Pregnant rats were exposed to a low dose of propylthiouracil (PTU, 0.0003%) through the drinking water during pregnancy and lactation. Dam and pup THs were quantified postnatally and RNA-Seq of the VZ performed in neonates. The PTU exposure resulted in a modest increase in maternal thyroid stimulating hormone and reduced thyroxine (T4). Exposed neonates exhibited hypothyroidism and T4 and triiodothyronine (T3) were also reduced in the telencephalon. RNA-Seq identified 358 differentially expressed genes in microdissected VZ cells of hypothyroid neonates as compared to controls (q-values ≤0.05). Pathway analyses showed processes like maintenance of the extracellular matrix and cytoskeleton, cell adhesion, and cell migration were significantly affected by hypothyroidism. Immunofluorescence also demonstrated that collagen IV, F-actin, radial glia, and adhesion proteins were reduced in the VZ. Immunohistochemistry of integrin αvβ3 and isoforms of both thyroid receptors (TRα/TRβ) showed highly overlapping expression patterns, including enrichment in the VZ. Taken together, our results show that TH action targets multiple components of cell junctions in the VZ, and this may be mediated by both genomic and nongenomic mechanisms. Surprisingly, this work also suggests that the blood-brain and blood-cerebrospinal fluid barriers may also be affected in hypothyroid newborns.

Located in modern-day eastern Türkiye, Ani was the ancient capital of the prosperous Armenian Bagratid period in the Middle Ages renowned as the “City of 1,001 Churches”. Unfortunately, due to a series of massive earthquakes, shifting trade routes and periodic conflict, Ani’s great buildings were abandoned before the 17th century, leaving the expansive ruins of the city unattended and exposed to the elements. World Monuments Fund (WMF) has maintained a presence at the site in Kars Province, Türkiye since its inclusion on the 1996 World Monuments Watch, which raised international awareness of the need for protection of this significant built fabric. The decades-long project has integrated professionals from Türkiye, Armenia, Iran, Russia and the United States, making the preservation of Ani a truly international endeavor and establishing a model for project-focused international collaboration. This paper sets forth some of the key considerations and components in the establishment of a collaborative preservation that facilitates regional coordination, international cooperation, and global cultural exchange.

Zinc (Zn)-anode batteries, although safe and non-flammable, are precluded from promising applications because of their low voltage (2 V) and poor rechargeability. Here, we report the fabrication of rechargeable membrane-less Zn-anode batteries with high voltage properties (2.5 to 3.4 V) achieved through coupling cathodes and Zn-anodes in gelled concentrated acid and alkaline solutions separated by a gelled buffer interlayer containing the working ions. The concentrated gelled buffer interlayers perform dual functions of regulating the pH of the system and acting as the source and sink of the working ions. With this strategy we show low-cost membrane-less 2.5 to 3.4 V Zn-manganese dioxide (MnO