Individualized Functional Brain System Topologies and Major Depression: Relationships Among Patch Sizes and Clinical Profiles and Behavior.

BACKGROUND: Neuroimaging studies of major depression have typically been conducted using group-level approaches. However, given interindividual differences in brain systems, there is a need for individualized approaches to brain systems mapping and putative links toward diagnosis, symptoms, and behavior. METHODS: We used an iterative parcellation approach to map individualized brain systems in 328 participants from a multisite, placebo-controlled clinical trial. We hypothesized that participants with depression would show abnormalities in salience, control, default, and affective systems, which would be associated with higher levels of self-reported anhedonia, anxious arousal, and worse cognitive performance. Within hypothesized brain systems, we compared patch sizes (number of vertices) between depressed and healthy control groups. Within depressed groups, abnormal patches were correlated with hypothesized clinical and behavioral measures. RESULTS: Significant group differences emerged in hypothesized patches of 1) the lateral salience system (parietal operculum; t326 = -3.11, p = .002) and 2) the control system (left medial posterior prefrontal cortex region; z = -3.63, p < .001), with significantly smaller patches in these regions in participants with depression than in healthy control participants. Results suggest that participants with depression with significantly smaller patch sizes in the lateral salience system and control system regions experience greater anxious arousal and cognitive deficits. CONCLUSIONS: The findings imply that neural features mapped at the individual level may relate meaningfully to diagnosis, symptoms, and behavior. There is strong clinical relevance in taking an individualized brain systems approach to mapping neural functional connectivity because these associated region patch sizes may help advance our understanding of neural features linked to psychopathology and foster future patient-specific clinical decision making.

Point of care detection of SARS-CoV-2 antibodies and neutralisation capacity-lateral flow immunoassay evaluation compared to commercial assay to inform potential role in therapeutic and surveillance practices.

Introduction: As the COVID-19 pandemic moves towards endemic status, testing strategies are being de-escalated. A rapid and effective point of care test (POCT) assessment of SARS-CoV-2 immune responses can inform clinical decision-making and epidemiological monitoring of the disease. This cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers assessed how rapid anti-SARS-CoV-2 antibody testing can be compared to a standard laboratory assay, discusses its effectiveness in neutralisation assessment and its uses into the future of the pandemic. Methods: A point of care lateral flow immunoassay (LFA) detecting anti-SARS-CoV-2 spike (S)-receptor binding domain (RBD) neutralising antibodies (Healgen SARS-CoV-2 neutralising Antibody Rapid Test Cassette) was compared to the Roche Elecsys/-S anti-SARS-CoV-2 antibody assays and an in vitro surrogate neutralisation assay. A correlation between anti-spike (S), anti-nucleocapsid (N) titres, and in vitro neutralisation was also assessed. Results: 1,777 serology samples were tested using Roche Elecsys/-S anti-SARS-CoV-2 assays to detect total anti-N/S antibodies. 1,562 samples were tested using the POC LFA (including 50 negative controls), and 90 samples were tested using an in vitro ACE2-RBD binding inhibition surrogate neutralisation assay. The POCT demonstrated 97.7% sensitivity, 100% specificity, a positive predictive value (PPV) of 100%, and a negative predictive value (NPV) of 61% in comparison to the commercial assay. Anti-S antibody titres determined by the Roche assay stratified by the POC LFA result groups demonstrated statistically significant differences between the "Positive" and "Negative" LFA groups (p < 0.0001) and the "Weak Positive" and "Positive" LFA groups (p < 0.0001). No statistically significant difference in ACE2-RBD binding inhibition was demonstrated when stratified by the LFA POC results. A positive, statistically significant correlation was demonstrated between the in vitro pseudo-neutralisation assay results and anti-S antibody titres (rho 0.423, p < 0.001) and anti-N antibody titres (rho = 0.55, p < 0.0001). Conclusion: High sensitivity, specificity, and PPV were demonstrated for the POC LFA for the detection of anti-S-RBD antibodies in comparison to the commercial assay. The LFA was not a reliable determinant of the neutralisation capacity of identified antibodies. POC LFA are useful tools in sero-epidemiology settings, pandemic preparedness and may act as supportive tools in treatment decisions through the rapid identification of anti-Spike antibodies.

Towards optical frequency geopotential difference measurements via a flying drone.

Geopotential and orthometric height differences between distant points can be measured via timescale comparisons between atomic clocks. Modern optical atomic clocks achieve statistical uncertainties on the order of 10-18, allowing height differences of around 1 cm to be measured. Frequency transfer via free-space optical links will be needed for measurements where linking the clocks via optical fiber is not possible, but requires line of sight between the clock locations, which is not always practical due to local terrain or over long distances. We present an active optical terminal, phase stabilization system, and phase compensation processing method robust enough to enable optical frequency transfer via a flying drone, greatly increasing the flexibility of free-space optical clock comparisons. We demonstrate a statistical uncertainty of 2.5×10-18 after 3 s of integration, corresponding to a height difference of 2.3 cm, suitable for applications in geodesy, geology, and fundamental physics experiments.

SARS-CoV-2 epidemiology, antibody dynamics, and neutralisation capacity in Irish healthcare workers in the era of booster COVID-19 vaccinations.

Background: The PRECISE Study, a multi-phase cross-sectional seroprevalence study of anti-SARS-CoV-2 antibodies in Irish healthcare workers (HCW) investigated: (1) risk factors for SARS-CoV-2 seropositivity, (2) the durability of antibody responses in a highly vaccinated HCW cohort, and (3) the neutralisation capacity of detected antibodies, prior to booster COVID-19 vaccination. Materials and methods: Serology samples were collected across two hospital sites in November 2021 and analysed using the Roche Elecsys Anti-SARS-CoV-2/Elecsys-S Anti-SARS-CoV-2 assays to detect anti-nucleocapsid (N) and anti-spike (S) antibodies respectively. Paired serology results from prior study phases were used to analyse changes in individual HCW serostatus over time. Risk-factors for SARS-CoV-2 infection were assessed for demographic and work-related factors. Antibody neutralisation capacity was assessed in a subset of samples via an in vitro ACE2 binding enzyme-linked immunosorbent assay. Results: 2,344 HCW samples were analysed. Median age was 43 years (IQR 33-50) with 80.5% (n = 1,886) female participants. Irish (78.9%, n = 1,850) and Asian (12.3%, n = 288) were the most commonly reported ethnicities. Nursing/midwifery (39.3%, n = 922) was the most common job role. 97.7% of participants were fully vaccinated, with Pfizer (81.1%, n = 1,902) and AstraZeneca (16.1%, n = 377) the most common vaccines received. Seroprevalence for anti-SARS-CoV-2 antibodies indicating prior infection was 23.4%, of these 33.6% represented previously undiagnosed infections. All vaccinated participants demonstrated positive anti-S antibodies and in those with paired serology, no individual demonstrated loss of previously positive anti-S status below assay threshold for positivity. Interval loss of anti-N antibody positivity was demonstrated in 8.8% of previously positive participants with paired results. Risk factors for SARS-CoV-2 seropositivity suggestive of previous infection included age 18-29 years (aRR 1.50, 95% CI 1.19-1.90, p < 0.001), India as country of birth (aRR 1.35, 95% CI 1.01-1.73, p = 0.036), lower education level (aRR 1.35, 95% CI 1.11-1.66, p = 0.004) and HCA job role (aRR 2.12, 95% CI 1.51-2.95, p < 0.001). Antibody neutralisation varied significantly by anti-SARS-CoV-2 antibody status, with highest levels noted in those anti-N positive, in particular those with vaccination plus previous SARS-CoV-2 infection. Conclusion: All vaccinated HCWs maintained anti-S positivity prior to COVID-19 booster vaccination, however anti-N positivity was more dynamic over time. Antibody neutralisation capacity was highest in participants with COVID-19 vaccination plus prior SARS-CoV-2 infection.

Adaptive optics LEO uplink pre-compensation with finite spatial modes.

Adaptive optics pre-compensation of free-space optical communications uplink from ground to space is complicated by the "point ahead angle" due to spacecraft velocity and the finite speed of light, as well as anisoplanatism of the uplink beam and the wavefront beacon. This Letter explores how pre-compensation varies with the number of spatial modes applied and how it varies with a beacon at the point-ahead angle versus a downlink beacon. Using a w0 = 16 cm Gaussian beam propagating through a modified Hufnagel-Valley model as an example, we find pre-compensation performance plateaus beyond ∼100 applied modes regardless of integrated turbulence strength, and that a point ahead beacon provides a 1-4 dB gain in median received power and an order-of-magnitude reduction in scintillation over a downlink beacon at wavelengths typical of optical communications. Modeling tailored to specific scenarios should be conducted to determine whether implementing a resource-intensive point ahead beacon is the optimum path to meeting link requirements.

Demonstration of 100 Gbps coherent free-space optical communications at LEO tracking rates.

Free-space optical communications are poised to alleviate the data-flow bottleneck experienced by spacecraft as traditional radio frequencies reach their practical limit. While enabling orders-of-magnitude gains in data rates, optical signals impose much stricter pointing requirements and are strongly affected by atmospheric turbulence. Coherent detection methods, which capitalize fully on the available degrees of freedom to maximize data capacity, have the added complication of needing to couple the received signal into single-mode fiber. In this paper we present results from a coherent 1550 nm link across turbulent atmosphere between a deployable optical terminal and a drone-mounted retroreflector. Through 10 Hz machine vision optical tracking with nested 200 Hz tip/tilt adaptive optics stabilisation, we corrected for pointing errors and atmospheric turbulence to maintain robust single mode fiber coupling, resulting in an uninterrupted 100 Gbps optical data link while tracking at angular rates of up to 1.5 deg/s, equivalent to that of spacecraft in low earth orbit. With the greater data capacity of coherent communications and compatibility with extant fiber-based technologies being demonstrated across static links, ground-to-low earth orbit links of Terabits per second can ultimately be achieved with capable ground stations.

Angle-of-arrival variability of retroreflected lasers despite atmospheric reciprocity.

Corner cube retroreflectors are commonly used as cooperative targets in free-space laser applications. The previous literature suggests that due to path reciprocity, a retroreflected beam is self-corrected across a turbulent atmosphere and should show no angle-of-arrival variability in the near field. This is at odds with recent experiments that rely on angle-of-arrival measurements in retroreflected beams for effective tip/tilt correction. In this Letter we investigate the mechanism behind observed angle-of-arrival variability using numerical field propagation to model various transceiver and retroreflector geometries. We determine that asymmetric truncation of a curved wavefront at the retroreflector, transceiver, or both, results in a difference in tip/tilt between the transmitted and reflected wavefronts. This difference propagates as angle-of-arrival variation at the transceiver despite reciprocity, providing the error signal necessary for adaptive optics tip/tilt correction without a remote beacon.

Vulnerability of Satellite Quantum Key Distribution to Disruption from Ground-Based Lasers.

Satellite-mediated quantum key distribution (QKD) is set to become a critical technology for quantum-secure communication over long distances. While satellite QKD cannot be effectively eavesdropped, we show it can be disrupted (or 'jammed') with relatively simple and readily available equipment. We developed an atmospheric attenuation and satellite optical scattering model to estimate the rate of excess noise photons that can be injected into a satellite QKD channel by an off-axis laser, and calculated the effect this added noise has on the quantum bit error rate. We show that a ground-based laser on the order of 1 kW can significantly disrupt modern satellite QKD systems due to photons scattering off the satellite being detected by the QKD receiver on the ground. This class of laser can be purchased commercially, meaning such a method of disruption could be a serious threat to effectively securing high-value communications via satellite QKD in the future. We also discuss these results in relation to likely future developments in satellite-mediated QKD systems, and countermeasures that can be taken against this, and related methods, of disruption.

Prostate carcinoma with positive margins at radical prostatectomy: role of tumour zonal origin in biochemical recurrence.

OBJECTIVE: To assess the influence of tumour zonality on biochemical recurrence (BCR) after radical prostatectomy (RP) with a histologically confirmed positive surgical margin (PSM). PATIENTS AND METHODS: Data from 382 patients that underwent RP with either transition zone (TZ) or peripheral zone (PZ) tumours involving PSMs between 1998 and 2010 were retrieved from the Abbott West Australian Prostatectomy Database. Statistical analysis was used to evaluate the relationship of various tumour clinicopathological parameters, e.g. zonal origin of tumour, tumour volume, Gleason score, and stage to the development of BCR RESULTS: There were 51 TZ and 331 PZ tumours with PSMs identified. The TZ tumours compared with PZ tumours were larger (median 5.67 vs 3.64 mL, P < 0.001), more frequently lower grade (Gleason score 6 33% vs 5%, P < 0.01), organ confined (51% vs 35.6%, P = 0.073), and preferentially involved the bladder neck (49% vs 6%, P < 0.001). Tumour zonality was not associated with BCR for the entire cohort. TZ and PZ tumours had similar 5-year BCR-free survival rates (58% vs 63%, P = 0.691) and comparable time to development of BCR (14.4 vs 19.2 months, P = 0.346). On univariate analysis, preoperative PSA level, PSM at the bladder neck, tumour volume, Gleason score (P < 0.001) and tumour stage were independent predictors of BCR for the entire cohort. On multivariate analysis tumour volume and Gleason score retained significance as independent predictors of BCR. Tumour zonality was not directly associated with BCR. Of the patients who received adjuvant therapy, the incidence of BCR was similar for TZ and PZ tumours (58% vs 67%, P = 0.077), although TZ tumours failed significantly earlier (mean 4.4 vs 16.4 months, P = 0.037). CONCLUSIONS: PSA recurrence in patients with histologically confirmed PSMs after RP is independent of the zonal location of the index tumour. However, tumour zonal origin may have an indirect influence on PSA relapse, as TZ tumours tend to be of large volume and more likely involve the bladder neck margin, both risk factors for BCR. Bladder neck margin involvement is associated with higher rates of BCR than other sites of PSMs. The preoperative identification of TZ tumours might aid surgical planning with appropriate alteration of RP technique to incorporate wider surgical margins at the bladder neck. Adjuvant radiotherapy appears to be associated with adverse outcome for TZ tumours, a novel finding which warrants further investigation.

Reliable identification of transition zone prostatic adenocarcinoma in preoperative needle core biopsy.

Prostatic adenocarcinomas arising within the transition zone (Tz) are distinct from peripheral zone (Pz) tumors as regards biological aggression and mechanism of extraprostatic extension. Reliable biopsy identification of Tz tumors would allow targeted surgical approaches more likely to preserve erectile function without compromising surgical margins. Previous studies have demonstrated the presence of eosinophilic cytoplasmic granules (prostate secretory granules, or PSGs) after glutaraldehye fixation, with apparent depletion in neoplasia. We investigated PSG content, columnar cells, pale cytoplasm, and luminal secretions of both Pz and Tz tumors in 44 radical prostatectomies (RPs) and 135 biopsies fixed with gluteraldehyde-based fixative. Retention of PSG is characteristic of Tz carcinoma and infrequently seen in Pz tumors, and a combination of PSG greater than 30% with either columnar cells, pale cells, or secretions in biopsies is a reliable marker for Tz origin. When these criteria were prospectively applied to 3929 cases with follow-up RP, 510 Tz tumors were correctly identified on biopsy (sensitivity, 21.4%; specificity, 97.4%). Biopsy-identified Tz tumors had higher volumes (mean, 3.48 versus 1.81 cm(3); P < .001) and higher rates of margin positivity (22.5% versus 17.5%; P = .008) than did Tz tumors not identified preoperatively. Mean Tz tumor length in biopsies was 2.0 mm, with no correlation between tumor volume at RP and tumor length on biopsy. Tz tumors are reliably identified on biopsy, based on a combination of PSG retention with either columnar cells, pale cells, or secretion. Biopsy-identified Tz tumors may not be suitable for active surveillance because of an associated high probability of large tumor volume and increased risk of positive margins at RP.