Rhesus infant nervous temperament predicts peri-adolescent central amygdala metabolism & behavioral inhibition measured by a machine-learning approach.

Anxiety disorders affect millions of people worldwide and impair health, happiness, and productivity on a massive scale. Developmental research points to a connection between early-life behavioral inhibition and the eventual development of these disorders. Our group has previously shown that measures of behavioral inhibition in young rhesus monkeys (Macaca mulatta) predict anxiety-like behavior later in life. In recent years, clinical and basic researchers have implicated the central extended amygdala (EAc)-a neuroanatomical concept that includes the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST)-as a key neural substrate for the expression of anxious and inhibited behavior. An improved understanding of how early-life behavioral inhibition relates to an increased lifetime risk of anxiety disorders-and how this relationship is mediated by alterations in the EAc-could lead to improved treatments and preventive strategies. In this study, we explored the relationships between infant behavioral inhibition and peri-adolescent defensive behavior and brain metabolism in 18 female rhesus monkeys. We coupled a mildly threatening behavioral assay with concurrent multimodal neuroimaging, and related those findings to various measures of infant temperament. To score the behavioral assay, we developed and validated UC-Freeze, a semi-automated machine-learning (ML) tool that uses unsupervised clustering to quantify freezing. Consistent with previous work, we found that heightened Ce metabolism predicted elevated defensive behavior (i.e., more freezing) in the presence of an unfamiliar human intruder. Although we found no link between infant-inhibited temperament and peri-adolescent EAc metabolism or defensive behavior, we did identify infant nervous temperament as a significant predictor of peri-adolescent defensive behavior. Our findings suggest a connection between infant nervous temperament and the eventual development of anxiety and depressive disorders. Moreover, our approach highlights the potential for ML tools to augment existing behavioral neuroscience methods.

Mitotic chromosomes are self-entangled and disentangle through a topoisomerase-II-dependent two-stage exit from mitosis.

The topological state of chromosomes determines their mechanical properties, dynamics, and function. Recent work indicated that interphase chromosomes are largely free of entanglements. Here, we use Hi-C, polymer simulations, and multi-contact 3C and find that, by contrast, mitotic chromosomes are self-entangled. We explore how a mitotic self-entangled state is converted into an unentangled interphase state during mitotic exit. Most mitotic entanglements are removed during anaphase/telophase, with remaining ones removed during early G1, in a topoisomerase-II-dependent process. Polymer models suggest a two-stage disentanglement pathway: first, decondensation of mitotic chromosomes with remaining condensin loops produces entropic forces that bias topoisomerase II activity toward decatenation. At the second stage, the loops are released, and the formation of new entanglements is prevented by lower topoisomerase II activity, allowing the establishment of unentangled and territorial G1 chromosomes. When mitotic entanglements are not removed in experiments and models, a normal interphase state cannot be acquired.

Purcell-enhanced single photons at telecom wavelengths from a quantum dot in a photonic crystal cavity.

Quantum dots are promising candidates for telecom single photon sources due to their tunable emission across the different low-loss telecommunications bands, making them compatible with existing fiber networks. Their suitability for integration into photonic structures allows for enhanced brightness through the Purcell effect, supporting efficient quantum communication technologies. Our work focuses on InAs/InP QDs created via droplet epitaxy MOVPE to operate within the telecoms C-band. We observe a short radiative lifetime of 340 ps, arising from a Purcell factor of 5, owing to integration of the QD within a low-mode-volume photonic crystal cavity. Through in-situ control of the sample temperature, we show both temperature tuning of the QD's emission wavelength and a preserved single photon emission purity at temperatures up to 25K. These findings suggest the viability of QD-based, cryogen-free C-band single photon sources, supporting applicability in quantum communication technologies.

A Pragmatic Randomized Trial Comparing Surgical Clipping and Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Surgical clipping and endovascular treatment are commonly used in patients with unruptured intracranial aneurysms. We compared the safety and efficacy of the 2 treatments in a randomized trial. MATERIALS AND METHODS: Clipping or endovascular treatments were randomly allocated to patients with one or more 3- to 25-mm unruptured intracranial aneurysms judged treatable both ways by participating physicians. The study hypothesized that clipping would decrease the incidence of treatment failure from 13% to 4%, a composite primary outcome defined as failure of aneurysm occlusion, intracranial hemorrhage during follow-up, or residual aneurysms at 1 year, as adjudicated by a core lab. Safety outcomes included new neurologic deficits following treatment, hospitalization of >5 days, and overall morbidity and mortality (mRS > 2) at 1 year. There was no blinding. RESULTS: Two hundred ninety-one patients were enrolled from 2010 to 2020 in 7 centers. The 1-year primary outcome, ascertainable in 290/291 (99%) patients, was reached in 13/142 (9%; 95% CI, 5%-15%) patients allocated to surgery and in 28/148 (19%; 95% CI, 13%-26%) patients allocated to endovascular treatments (relative risk: 2.07; 95% CI, 1.12-3.83; P = .021). Morbidity and mortality (mRS >2) at 1 year occurred in 3/143 and 3/148 (2%; 95% CI, 1%-6%) patients allocated to surgery and endovascular treatments, respectively. Neurologic deficits (32/143, 22%; 95% CI, 16%-30% versus 19/148, 12%; 95% CI, 8%-19%; relative risk: 1.74; 95% CI, 1.04-2.92; P = .04) and hospitalizations beyond 5 days (69/143, 48%; 95% CI, 40%-56% versus 12/148, 8%; 95% CI, 5%-14%; relative risk: 0.18; 95% CI, 0.11-0.31; P < .001) were more frequent after surgery. CONCLUSIONS: Surgical clipping is more effective than endovascular treatment of unruptured intracranial aneurysms in terms of the frequency of the primary outcome of treatment failure. Results were mainly driven by angiographic results at 1 year.

Glial TGFß activity promotes neuron survival in peripheral nerves.

Maintaining long, energetically demanding axons throughout the life of an animal is a major challenge for the nervous system. Specialized glia ensheathe axons and support their function and integrity throughout life, but glial support mechanisms remain poorly defined. Here, we identified a collection of secreted and transmembrane molecules required in glia for long-term axon survival in vivo. We showed that the majority of components of the TGFß superfamily are required in glia for sensory neuron maintenance but not glial ensheathment of axons. In the absence of glial TGFß signaling, neurons undergo age-dependent degeneration that can be rescued either by genetic blockade of Wallerian degeneration or caspase-dependent death. Blockade of glial TGFß signaling results in increased ATP in glia that can be mimicked by enhancing glial mitochondrial biogenesis or suppressing glial monocarboxylate transporter function. We propose that glial TGFß signaling supports axon survival and suppresses neurodegeneration through promoting glial metabolic support of neurons.

Soil microbial community structures are shaped by agricultural systems revealing little temporal variation.

Many studies in soil microbial ecology are undertaken with a single sampling event, with the influence of temporal progression rarely being considered. Under field conditions, soil samples were taken from different agricultural systems; a sown grassland to maize rotation (MC), an intensively managed permanent grassland (INT), as well as extensively managed permanent grasslands with high (EXT_HP), low to sufficient (EXT_LP) and deficient available P (EXT_DP), six times throughout the 2017 growing season. Thus, this study aimed to determine if any differences in soil microbiome structures between both sharply contrasting (MC - INT - EXT), slightly differing (EXT_HP - EXT_DP) and quite similar (EXT_HP - EXT_LP and EXT_LP - EXT_DP) agricultural systems persist through changing growth conditions within the growing season. For both fungal and bacterial community structure, the influence of agricultural system (CV = 0.256, P < 0.001 and CV = 0.145, P < 0.01, respectively) was much greater than that of temporal progression (√CV = 0.065 and 0.042, respectively, both P < 0.001). Importantly, nearly all agricultural systems persistently harbored significantly distinct fungal community structures across each of the six sampling events (all at least P < 0.05). There were not as many pairwise differences in bacterial community structure between the agricultural systems, but some did persist (MC and EXT_HP âˆ¼ EXT_DP, all P < 0.001). Additionally, persistent indicator fungal OTUs (IndVal >0.7, P ≤ 0.05) associated to each agricultural system (except EXT_LP) were found in each of the six sampling events. These results highlight the temporal stability of pairwise differences in soil microbiome structures between established agricultural systems through changing plant growth conditions, even between those with a comparable management regime. This is a highly relevant finding in informing the sampling strategy of studies in soil microbial ecology as well as for designing efficient soil biodiversity monitoring systems.

VBNC, previously unrecognized in the life cycle of Porphyromonas gingivalis?

Bacteria are exposed to stresses during their growth and multiplication in their ecological systems to which they respond in multiple ways as expert survivalists. One such response mechanism is to convert to a viable but not culturable (VBNC) state. As the name indicates, bacteria in the VBNC state have lost their ability to grow on routine growth medium. A large number of bacteria including many pathogenic species have been reported to be able to enter a VBNC state. VBNC differs from culturable cells in various physiological properties which may result in changes in chemical resistance, adhesion, cellular morphology, metabolism, gene expression, membrane and cell wall composition and/or virulence. The ability of VBNC bacteria to return to the culturable state or resuscitate, when the stressor is removed poses a considerable threat to public health. There have been few publications that overtly describe the ability of oral pathogenic species to enter the VBNC state. However, the presence of VBNCs among oral pathogens such as Porphyromonas gingivalis in human chronic infections may be an important virulence factor and have severe implications for therapy. In this review, we intend to i) define and summarize the significance of the VBNC state in general and ii) discuss the VBNC state of oral bacteria with regard to P. gingivalis. Future studies focused on this phenomenon of intraoral VBNC would provide novel molecular insights on the virulence and persistence of oral pathogens during chronic infections and identify potential novel therapies.

Small-scale agricultural grassland management can affect soil fungal community structure as much as continental scale geographic patterns.

A European transect was established, ranging from Sweden to the Azores, to determine the relative influence of geographic factors and agricultural small-scale management on the grassland soil microbiome. Within each of five countries (factor 'Country'), which maximized a range of geographic factors, two differing growth condition regions (factor 'GCR') were selected: a favorable region with conditions allowing for high plant biomass production and a contrasting less favorable region with a markedly lower potential. Within each region, grasslands of contrasting management intensities (factor 'MI') were defined: intensive and extensive, from which soil samples were collected. Across the transect, 'MI' was a strong differentiator of fungal community structure, having a comparable effect to continental scale geographic factors ('Country'). 'MI' was also a highly significant driver of bacterial community structure, but 'Country' was clearly the stronger driver. For both, 'GCR' was the weakest driver. Also at the regional level, strong effects of MI occurred on various measures of the soil microbiome (i.e. OTU richness, management-associated indicator OTUs), though the effects were largely regional-specific. Our results illustrate the decisive influence of grassland MI on soil microbial community structure, over both regional and continental scales, and, thus, highlight the importance of preserving rare extensive grasslands.

Bright single photon emitters with enhanced quantum efficiency in a two-dimensional semiconductor coupled with dielectric nano-antennas.

Single photon emitters in atomically-thin semiconductors can be deterministically positioned using strain induced by underlying nano-structures. Here, we couple monolayer WSe2 to high-refractive-index gallium phosphide dielectric nano-antennas providing both optical enhancement and monolayer deformation. For single photon emitters formed on such nano-antennas, we find very low (femto-Joule) saturation pulse energies and up to 104 times brighter photoluminescence than in WSe2 placed on low-refractive-index SiO2 pillars. We show that the key to these observations is the increase on average by a factor of 5 of the quantum efficiency of the emitters coupled to the nano-antennas. This further allows us to gain new insights into their photoluminescence dynamics, revealing the roles of the dark exciton reservoir and Auger processes. We also find that the coherence time of such emitters is limited by intrinsic dephasing processes. Our work establishes dielectric nano-antennas as a platform for high-efficiency quantum light generation in monolayer semiconductors.

Symptoms and laboratory manifestations of mild COVID-19 in a repatriated cruise ship cohort.

Much of our current understanding about novel coronavirus disease 2019 (COVID-19) comes from hospitalised patients. However, the spectrum of mild and subclinical disease has implications for population-level screening and control. Forty-nine participants were recruited from a group of 99 adults repatriated from a cruise ship with a high incidence of COVID-19. Respiratory and rectal swabs were tested by polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sera were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and microneutralisation assay. Symptoms, viral shedding and antibody response were examined. Forty-five participants (92%) were considered cases based on either positive PCR or positive ELISA for immunoglobulin G. Forty-two percent of cases were asymptomatic. Only 15% of symptomatic cases reported fever. Serial respiratory and rectal swabs were positive for 10% and 5% of participants respectively about 3 weeks after median symptom onset. Cycle threshold values were high (range 31-45). Attempts to isolate live virus were unsuccessful. The presence of symptoms was not associated with demographics, comorbidities or antibody response. In closed settings, incidence of COVID-19 could be almost double that suggested by symptom-based screening. Serology may be useful in diagnosis of mild disease and in aiding public health investigations.

COVID-19 testing in outbreak-free care homes: what are the public health benefits?

BACKGROUND: COVID-19 care home outbreaks represent a significant proportion of COVID-19 morbidity and mortality in the UK. National testing initially focused on symptomatic care home residents, before extending to asymptomatic cohorts. AIM: The aim was to describe the epidemiology and transmission of COVID-19 in outbreak free care homes. METHODS: A two-point prevalence survey of COVID-19, in 34 Liverpool care homes, was performed in April and May 2020. Changes in prevalence were analysed. Associations between care home characteristics, reported infection, prevention and control interventions, and COVID-19 status were described and analysed. FINDINGS: No resident developed COVID-19 symptoms during the study. There was no significant difference between: the number of care homes containing at least one test positive resident between the first (17.6%, 95% confidence interval (CI) 6.8-34.5) and second round (14.7%, 95% CI 5.0-31.1) of testing (p>0.99); and the number of residents testing positive between the first (2.1%, 95% CI 1.2-3.4) and second round (1.0%, 95% CI 0.5-2.1) of testing (P=0.11). Care homes providing nursing care (risk ratio (RR) 7.99, 95% CI 1.1-57.3) and employing agency staff (RR 8.4, 95% CI 1.2-60.8) were more likely to contain test positive residents. Closing residents shared space was not associated with residents testing positive (RR 2.63, 95% CI 0.4-18.5). CONCLUSIONS: Asymptomatic COVID-19 care homes showed no evidence of disease transmission or development of outbreaks; suggesting that current infection prevention and control measures are effective in preventing transmission. Repeat testing at two to three weeks had limited or no public health benefits over regular daily monitoring of staff and residents for symptoms. These results should inform policies calling for regular testing of asymptomatic residents.

The Magellanic Corona as the key to the formation of the Magellanic Stream.

The dominant gaseous structure in the Galactic halo is the Magellanic Stream. This extended network of neutral and ionized filaments surrounds the Large Magellanic Cloud (LMC) and the Small Magellanic Cloud (SMC), the two most massive satellite galaxies of the Milky Way1-4. Recent observations indicate that the LMC and SMC are on their first passage around the Galaxy5, that the Magellanic Stream is made up of gas stripped from both clouds2,6,7 and that the majority of this gas is ionized8,9. Although it has long been suspected that tidal forces10,11 and ram-pressure stripping12,13 contributed to the formation of the Magellanic Stream, models have not been able to provide a full understanding of its origins3. Several recent developments-including the discovery of dwarf galaxies associated with the Magellanic group14-16, determination of the high mass of the LMC17, detection of highly ionized gas near stars in the LMC18,19 and predictions of cosmological simulations20,21-support the existence of a halo of warm (roughly 500,000 kelvin) ionized gas around the LMC (the 'Magellanic Corona'). Here we report that, by including this Magellanic Corona in hydrodynamic simulations of the Magellanic Clouds falling onto the Milky Way, we can reproduce the Magellanic Stream and its leading arm. Our simulations explain the filamentary structure, spatial extent, radial-velocity gradient and total ionized-gas mass of the Magellanic Stream. We predict that the Magellanic Corona will be unambiguously observable via high-ionization absorption lines in the ultraviolet spectra of background quasars lying near the LMC.

Using geospatial methods to measure the risk of environmental persistence of avian influenza virus in South Carolina.

Avian influenza (AIV) is a highly contagious virus that can infect both wild birds and domestic poultry. This study aimed to define areas within the state of South Carolina (SC) at heightened risk for environmental persistence of AIV using geospatial methods. Environmental factors known to influence AIV survival were identified through the published literature and using a multi-criteria decision analysis with GIS was performed. Risk was defined using five categories following the World Organization for Animal Health Risk Assessment Guidelines. Less than 1% of 1km grid cells in SC showed a high risk of AIV persistence. Approximately 2% - 17% of counties with high or very high environmental risk also had medium to very high numbers of commercial poultry operations. Results can be used to improve surveillance activities and to inform biosecurity practices and emergency preparedness efforts.

Abdominal adiposity assessed using CT angiography associates with acute kidney injury after trans-catheter aortic valve replacement.

AIM: To determine if there is an association between area-based visceral abdominal adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAT), and abdominal circumference measured on computed tomography (CT) angiography before trans-catheter aortic valve replacement (TAVR) and post-TAVR acute kidney injury (AKI). MATERIALS AND METHODS: In this retrospective cohort study of 106 TAVR patients, SAT and VAT areas and abdominal circumference was measured on a single CT section at L4 vertebral level. Univariate comparisons between patients who did and did not develop AKI were undertaken for radiological measurements. Multivariable logistic regression was used to assess association between CT measurements and the development of post-TAVR AKI. RESULTS: Post-TAVR AKI occurred in 20 of 106 patients (19%). In univariate comparisons, body mass index (BMI) did not differ significantly between patients who did and did not develop AKI (p=0.14); however, VAT+SAT (443.2±163.7 versus 351±168.7 cm2; p=0.03), VAT (213.9±110.6 versus 153.9±96.1 cm2; p=0.03), and outer abdominal circumference (100.2±14.4 cm versus 91.8±13.3 cm; p=0.02) were significantly higher in the patients who did not develop post-TAVR AKI. These three measures on pre-TAVR CT angiogram remained significantly associated with reduced post-TAVR AKI with a lower incidence of post-TAVR AKI after multivariable adjustment for pre-TAVR estimated glomerular filtration rate and patient height (p<0.05). CONCLUSION: This study found that increased abdominal obesity as assessed by measures on pre-TAVR CT angiogram is associated with a significantly lower incidence of AKI.

Photon Statistics of Filtered Resonance Fluorescence.

Spectral filtering of resonance fluorescence is widely employed to improve single photon purity and indistinguishability by removing unwanted backgrounds. For filter bandwidths approaching the emitter linewidth, complex behavior is predicted due to preferential transmission of components with differing photon statistics. We probe this regime using a Purcell-enhanced quantum dot in both weak and strong excitation limits, finding excellent agreement with an extended sensor theory model. By changing only the filter width, the photon statistics can be transformed between antibunched, bunched, or Poissonian. Our results verify that strong antibunching and a subnatural linewidth cannot simultaneously be observed, providing new insight into the nature of coherent scattering.

Polypharmacy and potential drug-drug interactions for people with HIV in the UK from the Climate-HIV database.

OBJECTIVES: People with HIV (PWHIV) are likely to need therapies for comorbidities as they age. We assessed risk of drug-drug interactions (DDIs) in PWHIV. METHODS: The Climate-HIV electronic recording system was used to cross-sectionally analyse records from PWHIV aged ≥ 18 years attending four UK HIV units with a current antiretroviral (ARV) prescription in February 2018. Antiretroviral and non-ARV medications were categorized by clinical significance of DDIs (University of Liverpool DDI tool). Potential DDIs were predicted using treatment guidelines for commonly recorded comorbidities. RESULTS: Among 4630 PWHIV (44% female), 41% were ≥ 50 years old. The average number of non-ARV comedications increased from < 1 for patients aged ≤ 24 years to > 5 for patients aged ≥ 75 years; 65% were taking one or more non-ARV comedications. The median (interquartile range) number of non-ARVs was 1 (0-2) and 2 (1-5) for those aged < 50 and ≥ 50 years, respectively. Common comorbidities/concurrent health conditions occurred more frequently in patients aged ≥ 50 years vs. < 50 (53% vs. 34%). Boosted protease inhibitors were associated with the highest proportion of contraindicated comedications; dolutegravir and raltegravir had the fewest. For non-ARVs, sildenafil and quetiapine were most likely to result in DDIs. Guideline-recommended treatments for hepatitis C, hepatitis B, and tuberculosis had the highest proportions of contraindications when combined with ARV regimens, while treatments for hepatitis C, malignancy, and mental health conditions had the highest proportion of combinations potentially causing DDIs requiring dose monitoring or adjustment. CONCLUSIONS: Non-ARV use by PWHIV is high and increases with age. Treatment decisions for ageing PWHIV should consider guideline recommendations for comorbidities.

Porphyromonas gingivalis W83 traffics via ICAM1 in microvascular endothelial cells and alters capillary organization in vivo.

Objective: Microvascular dysfunction is a feature of periodontal disease. P. gingivalis, one of the most common oral bacteria present in gingival tissue biofilms, has also been identified in the gingival capillaries of patients with chronic periodontitis. We sought to determine the effect of P. gingivalis W83 infection on microvascular endothelium in vivo and in vitro. Methods and Results: Interdental papillae of rats with P. gingivalis-induced alveolar bone loss had a more dilated and denser subepithelial capillary network than uninfected controls. P. gingivalis W83 was detected in the epithelial layers, the subepithelial connective tissue matrix, and subgingival capillaries. P. gingivalis invaded human dermal microvascular endothelial cells (HD-MVECS) and persisted up termination (24 h). Colocalization analysis at 2.5, 6, and 24 h post-inoculation showed that 79-88% of internalized bacteria were in ICAM-1 positive endosomes, and 10-39% were in Rab5, Rab7, or LAMP1 positive compartments, but never in autophagosomes. Antibody-based blockade of ICAM-1 significantly reduced W83 invasion in HD-MVECS. P. gingivalis infected HD-MVECS were unable to form vascular networks in Matrigel. Conclusions: P. gingivalis perturbs microvascular endothelial function and invasion of these cells via ICAM-1 may be important for microbial persistence within tissues.

OPTN/SRTR 2018 Annual Data Report: Pancreas.

The overall number of pancreas transplants continued to increase to 1027 in 2018, after a nadir of 947 in 2015. New additions to waiting list remained stable, with 1485 candidates added in 2018. Proportions of patients with type II diabetes waiting for transplant (14.6%) and undergoing transplant (14.8%) have steadily increased since 2016. Waiting times for simultaneous pancreas/kidney transplant have decreased; median months to transplant was 13.5 for simultaneous pancreas/kidney transplant and 19.7 for pancreas transplant alone in 2018. Outcomes, including patient and kidney survival, as well as rejection rates, have improved consistently over the past several years. Pancreas graft survival data are being collected by the Organ Procurement and Transplantation Network and will be included in a future report once there are sufficient cohorts for analysis.

Light Scattering from Solid-State Quantum Emitters: Beyond the Atomic Picture.

Coherent scattering of light by a single quantum emitter is a fundamental process at the heart of many proposed quantum technologies. Unlike atomic systems, solid-state emitters couple to their host lattice by phonons. Using a quantum dot in an optical nanocavity, we resolve these interactions in both time and frequency domains, going beyond the atomic picture to develop a comprehensive model of light scattering from solid-state emitters. We find that even in the presence of a low-Q cavity with high Purcell enhancement, phonon coupling leads to a sideband that is completely insensitive to excitation conditions and to a nonmonotonic relationship between laser detuning and coherent fraction, both of which are major deviations from atomlike behavior.