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Abstract The quantitative characterization and prediction of localized severe weather events that emerge as coherences generated by the highly non-linear interacting multivariate dynamics of global weather systems poses a significant challenge whose solution is increasingly important in the face of climate change where weather extremes are on the rise. As weather measurement systems (multiband satellite, radar, etc) continue to dramatically improve, increasingly complex time-dependent multivariate 3D datasets offer the potential to inform such problems but pose an increasingly daunting computational challenge. Here we describe the application to global weather systems of a novel computational method called the Entropy Field Decomposition (EFD) capable of efficiently characterizing coherent spatiotemporal structures in non-linear multivariate interacting physical systems. Using the EFD derived system configurations, we demonstrate the application of a second novel computational method called Space-Time Information Trajectories (STITs) that reveal how spatiotemporal coherences are dynamically connected. The method is demonstrated on the specific phenomenon known as atmospheric rivers (ARs) which are a prime example of a highly coherent, in both space and time, severe weather phenomenon whose generation and persistence are influenced by weather dynamics on a wide range of spatial and temporal scales. The EFD reveals how the interacting wind vector field and humidity scalar field couple to produce ARs, while the resulting STITS reveal the linkage between ARs and large-scale planetary circulations. The focus on ARs is also motivated by their devastating social and economic effects that have made them the subject of increasing scientific investigation to which the EFD may offer new insights. The application of EFD and STITs to the broader range of severe weather events is discussed.

Abstract Acoustic communication is widespread in beetles, is often sexually dimorphic, and plays a significant role in behaviours such as premating recognition, courtship, and copulation. However, the factors that determine the presence or absence of acoustic signalling in a given species remain unclear. We examined acoustic communication in bark beetles (Scolytinae) and pinhole borers (Platypodinae), which are two speciose groups with widespread sound production capabilities. We show that body size along with the sequence of host colonisation predict the presence of acoustic communication, and report, for the first time in the animal kingdom, a size limit—1.9 mm—below which acoustic signalling ceases to be present.

During a pitfall trapping study in a coastal area of Central Norway (2002, 2003), three new species of ground beetles (Coleoptera, Carabidae) were recorded in North Trøndelag County: Notiophilus palustris (Duftschmid, 1812), Cymindis vaporariorum (L., 1758) and Amara aenea (Degeer, 1774). In addition, 14 species were recorded new to the coastal parts of the county, where the total number of carabids known to occur stands at 46. There are 111 recorded carabid species in North Trøndelag. The distributions of the species recorded new for North Trøndelag are discussed in the context of spreading abilities.

IntroductionThis is a prospective, rigorous inquiry into the systemic immune effects of standard adjuvant chemoradiotherapy, for WHO grade 4, glioblastoma. The purpose is to identify peripheral immunologic effects never yet reported in key immune populations, including myeloid-derived suppressor cells, which are critical to the immune suppressive environment of glioblastoma. We hypothesize that harmful immune-supportive white blood cells, myeloid derived suppressor cells, expand in response to conventionally fractionated radiotherapy with concurrent temozolomide, essentially promoting systemic immunity similar what is seen in chronic diseases like diabetes and heart disease.Methods16 patients were enrolled in a single-institution, observational, immune surveillance study where peripheral blood was collected and interrogated by flow cytometry and RNAseq. Tumor tissue from baseline assessment was analyzed with spatial proteomics to link peripheral blood findings to baseline tissue characteristics.ResultsWe identified an increase in myeloid-derived suppressor cells during the final week of a six-week treatment of chemoradiotherapy in peripheral blood of patients that were not alive at two years after diagnosis compared to those who were living. This was also associated with a decrease in CD8+ T lymphocytes that produced IFNγ, the potent anti-tumor cytokine.DiscussionThese data suggest that, as in chronic inflammatory disease, systemic immunity is impaired following delivery of adjuvant chemoradiotherapy. Finally, baseline investigation of myeloid cells within tumor tissue did not differ between survival groups, indicating immune surveillance of peripheral blood during adjuvant therapy may be a critical missing link to educate our understanding of the immune effects of standard of care therapy for glioblastoma.

Current diagnostic and therapeutic approaches for gliomas have limitations hindering survival outcomes. We propose spectroscopic magnetic resonance imaging as an adjunct to standard MRI to bridge these gaps. Spectroscopic MRI is a volumetric MRI technique capable of identifying tumor infiltration based on its elevated choline (Cho) and decreased N-acetylaspartate (NAA). We present the clinical translatability of spectroscopic imaging with a Cho/NAA ≥ 5x threshold for delineating a biopsy target in a patient diagnosed with non-enhancing glioma. Then, we describe the relationship between the undertreated tumor detected with metabolite imaging and overall survival (OS) from a pilot study of newly diagnosed GBM patients treated with belinostat and chemoradiation. Each cohort (control and belinostat) were split into subgroups using the median difference between pre-radiotherapy Cho/NAA ≥ 2x and the treated T1-weighted contrast-enhanced (T1w-CE) volume. We used the Kaplan–Meier estimator to calculate median OS for each subgroup. The median OS was 14.4 months when the difference between Cho/NAA ≥ 2x and T1w-CE volumes was higher than the median compared with 34.3 months when this difference was lower than the median. The T1w-CE volumes were similar in both subgroups. We find that patients who had lower volumes of undertreated tumors detected via spectroscopy had better survival outcomes.

Abstract Background Recruitment of participants is the greatest risk to completion of most clinical trials, with 20–40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke. We report on the experience using a novel hybrid recruitment approach of a patient-facing portal to self-identify and perform an initial screen for general trial eligibility (tier 1), followed by phone screening and medical records review (tier 2) prior to a final in-person visit to confirm eligibility and consent. Methods Two tiers of screening were established: an initial screen of general eligibility using a patient-facing web portal (tier 1), followed by a more detailed screen that included phone survey and medical record review (tier 2). If potential participants passed the tier 2 screen, they were referred directly to visit 1 at a study site, where final in-person screening and consent were performed. Rates of screening were tracked during the period of trial recruitment and sources of referrals were noted. Results The approach to screening and recruitment resulted in 6125 tier 1 screens, leading to 1121 referrals to tier 2. The tier 2 screening resulted in 224 medical record requests and identification of 86 qualifying participants for referral to sites. The study attained a viable recruitment rate of 6 enrolled per month prior to being disrupted by COVID 19. Conclusions A tiered approach to eligibility screening using a hybrid of web-based portals to self-identify and screen for general eligibility followed by a more detailed phone and medical record review allowed the study to use fewer sites and reduce cost. Despite the difficult and narrow population of patients suffering moderate chronic disability from stroke, this strategy produced a viable recruitment rate for this invasive study of intracranially injected neural stem cells. Trial registration ClinicalTrials.gov Identifier: NCT03629275

Abstract Some sources report increases in alcohol use have been observed since the start of the COVID-19 pandemic, particularly among women. Cross-sectional studies suggest that specific COVID-19-related stressful experiences (e.g., social disconnection) may be driving such increases in the general population. Few studies have explored these topics among individuals with a history of Alcohol Use Disorders (AUD), an especially vulnerable population. Drawing on recent data collected by the Collaborative Study on the Genetics of Alcoholism (COGA; COVID-19 study N = 1651, 62% women, age range: 30–91) in conjunction with AUD history data collected on the sample since 1990, we investigated associations of COVID-19 related stressors and coping activities with changes in drunkenness frequency since the start of the pandemic. Analyses were conducted for those without a history of AUD (N: 645) and three groups of participants with a history of AUD prior to the start of the pandemic: (1) those experiencing AUD symptoms (N: 606), (2) those in remission who were drinking (N: 231), and (3) those in remission who were abstinent (had not consumed alcohol for 5+ years; N: 169). Gender-stratified models were also examined. Exploratory analyses examined the moderating effects of ‘problematic alcohol use’ polygenic risk scores (PRS) and neural connectivity (i.e., posterior interhemispheric alpha EEG coherence) on associations between COVID-19 stressors and coping activities with changes in the frequency of drunkenness. Increases in drunkenness frequency since the start of the pandemic were higher among those with a lifetime AUD diagnosis experiencing symptoms prior to the start of the pandemic (14% reported increased drunkenness) when compared to those without a history of AUD (5% reported increased drunkenness). Among individuals in remission from AUD prior to the start of the pandemic, rates of increased drunkenness were 10% for those who were drinking pre-pandemic and 4% for those who had previously been abstinent. Across all groups, women reported nominally greater increases in drunkenness frequency when compared with men, although only women experiencing pre-pandemic AUD symptoms reported significantly greater rates of increased drunkenness since the start of the pandemic compared to men in this group (17% of women vs. 5% of men). Among those without a prior history of AUD, associations between COVID-19 risk and protective factors with increases in drunkenness frequency were not observed. Among all groups with a history of AUD (including those with AUD symptoms and those remitted from AUD), perceived stress was associated with increases in drunkenness. Among the remitted-abstinent group, essential worker status was associated with increases in drunkenness. Gender differences in these associations were observed: among women in the remitted-abstinent group, essential worker status, perceived stress, media consumption, and decreased social interactions were associated with increases in drunkenness. Among men in the remitted-drinking group, perceived stress was associated with increases in drunkenness, and increased relationship quality was associated with decreases in drunkenness. Exploratory analyses indicated that associations between family illness or death with increases in drunkenness and increased relationship quality with decreases in drunkenness were more pronounced among the remitted-drinking participants with higher PRS. Associations between family illness or death, media consumption, and economic hardships with increases in drunkenness and healthy coping with decreases in drunkenness were more pronounced among the remitted-abstinent group with lower interhemispheric alpha EEG connectivity. Our results demonstrated that only individuals with pre-pandemic AUD symptoms reported greater increases in drunkenness frequency since the start of the COVID-19 pandemic compared to those without a lifetime history of AUD. This increase was more pronounced among women than men in this group. However, COVID-19-related stressors and coping activities were associated with changes in the frequency of drunkenness among all groups of participants with a prior history of AUD, including those experiencing AUD symptoms, as well as abstinent and non-abstinent participants in remission. Perceived stress, essential worker status, media consumption, social connections (especially for women), and relationship quality (especially for men) are specific areas of focus for designing intervention and prevention strategies aimed at reducing pandemic-related alcohol misuse among this particularly vulnerable group. Interestingly, these associations were not observed for individuals without a prior history of AUD, supporting prior literature that demonstrates that widespread stressors (e.g., pandemics, terrorist attacks) disproportionately impact the mental health and alcohol use of those with a prior history of problems.

Abstract Optical layer attacks on optical fiber communication networks are one of the weakest reinforced areas of the network, allowing attackers to overcome security software or firewalls when proper safeguards are not put into place. Encrypting data using a random phase mask is a simple yet effective way to bolster the data security at the physical layer. Since the interactions of the random phases used for such encryption heavily depend on system properties like data rate, modulation format, distance, degree of phase randomness, laser properties, etc., it is important to determine the optimum operating conditions for different scenarios. In this work, assuming that the transmitter and the receiver have a secret pre-shared key, we present a theoretical study of security in such a system through mutual information analysis. Next, we determine operating conditions which ensure security for 4-PSK, 16-PSK, and 128-QAM formats through numerical simulation. Moreover, we provide an experimental demonstration of the system using 16-QAM modulation. We then use numerical simulation to verify the efficacy of the encryption and study two preventative measures for different modulation formats which will prevent an eavesdropper from obtaining any data. The results demonstrate that the system is secure against a tapping attack if an attacker has no information of the phase modulator and pre-shared key.

Histone deacetylase inhibitors (HDACis) are drugs that target the epigenetic state of cells by modifying the compaction of chromatin through effects on histone acetylation. Gliomas often harbor a mutation of isocitrate dehydrogenase (IDH) 1 or 2 that leads to changes in their epigenetic state presenting a hypermethylator phenotype. We postulated that glioma cells with IDH mutation, due to the presence of epigenetic changes, will show increased sensitivity to HDACis. This hypothesis was tested by expressing mutant IDH1 with a point alteration—converting arginine 132 to histidine—within glioma cell lines that contain wild-type IDH1. Glioma cells engineered to express mutant IDH1 produced D-2-hydroxyglutarate as expected. When assessed for response to the pan-HDACi drug belinostat, mutant IDH1-expressing glioma cells were subjected to more potent inhibition of growth than the corresponding control cells. Increased sensitivity to belinostat correlated with the increased induction of apoptosis. Finally, a phase I trial assessing the addition of belinostat to standard-of-care therapy for newly diagnosed glioblastoma patients included one patient with a mutant IDH1 tumor. This mutant IDH1 tumor appeared to display greater sensitivity to the addition of belinostat than the other cases with wild-type IDH tumors based on both standard magnetic resonance imaging (MRI) and advanced spectroscopic MRI criteria. These data together suggest that IDH mutation status within gliomas may serve as a biomarker of response to HDACis.

Accurate radiation therapy (RT) targeting is crucial for glioblastoma treatment but may be challenging using clinical imaging alone due to the infiltrative nature of glioblastomas. Precise targeting by whole-brain spectroscopic MRI, which maps tumor metabolites including choline (Cho) and N-acetylaspartate (NAA), can quantify early treatment-induced molecular changes that other traditional modalities cannot measure. We developed a pipeline to determine how spectroscopic MRI changes during early RT are associated with patient outcomes to provide insight into the utility of adaptive RT planning. Data were obtained from a study (NCT03137888) where glioblastoma patients received high-dose RT guided by the pre-RT Cho/NAA twice normal (Cho/NAA ≥ 2x) volume, and received spectroscopic MRI scans pre- and mid-RT. Overlap statistics between pre- and mid-RT scans were used to quantify metabolic activity changes after two weeks of RT. Log-rank tests were used to quantify the relationship between imaging metrics and patient overall and progression-free survival (OS/PFS). Patients with lower Jaccard/Dice coefficients had longer PFS (p = 0.045 for both), and patients with lower Jaccard/Dice coefficients had higher OS trending towards significance (p = 0.060 for both). Cho/NAA ≥ 2x volumes changed significantly during early RT, putting healthy tissue at risk of irradiation, and warranting further study into using adaptive RT planning.

Abstract The effectiveness, robustness, and flexibility of memory and learning constitute the very essence of human natural intelligence, cognition, and consciousness. However, currently accepted views on these subjects have, to date, been put forth without any basis on a true physical theory of how the brain communicates internally via its electrical signals. This lack of a solid theoretical framework has implications not only for our understanding of how the brain works, but also for wide range of computational models developed from the standard orthodox view of brain neuronal organization and brain network derived functioning based on the Hodgkin–Huxley ad-hoc circuit analogies that have produced a multitude of Artificial, Recurrent, Convolution, Spiking, etc., Neural Networks (ARCSe NNs) that have in turn led to the standard algorithms that form the basis of artificial intelligence (AI) and machine learning (ML) methods. Our hypothesis, based upon our recently developed physical model of weakly evanescent brain wave propagation (WETCOW) is that, contrary to the current orthodox model that brain neurons just integrate and fire under accompaniment of slow leaking, they can instead perform much more sophisticated tasks of efficient coherent synchronization/desynchronization guided by the collective influence of propagating nonlinear near critical brain waves, the waves that currently assumed to be nothing but inconsequential subthreshold noise. In this paper we highlight the learning and memory capabilities of our WETCOW framework and then apply it to the specific application of AI/ML and Neural Networks. We demonstrate that the learning inspired by these critically synchronized brain waves is shallow, yet its timing and accuracy outperforms deep ARCSe counterparts on standard test datasets. These results have implications for both our understanding of brain function and for the wide range of AI/ML applications.

Objective. The Children’s Hospitals in Africa Mapping Project survey was developed and implemented to assess the readiness of hospitals in sub-Saharan African to respond to emergencies, epidemics, and pandemics affecting children. Methods. This sub-study analyzed 56 survey questions that characterized the hospitals and assessed resources for diagnosis, treatment, and prevention of community-acquired infections and healthcare-associated infections (HAIs). Results. Twenty-four sites were recruited and 20 (from 15 countries) completed the survey in 2018 to 2019. Overall, 90% to 100% of sites reported that diagnostic assays were available for malaria, tuberculosis, and HIV. Periodic shortages of antibiotics, antimalarial drugs, and vaccines were reported by 45%, 25%, and 20% of sites, respectively. Sites reported formal programs for infection prevention and control (79%), monitoring HAIs (17%), and antimicrobial stewardship (53%). Conclusions. Opportunities to improve care for hospitalized African children were identified. These included resources for HAI surveillance and antimicrobial stewardship which can facilitate epidemic and pandemic preparedness.

IntroductionTreatment for glioblastomas, aggressive and nearly uniformly fatal brain tumors, provide limited long-term success. Immunosuppression by myeloid cells in both the tumor microenvironment and systemic circulation are believed to contribute to this treatment resistance. Standard multi-modality therapy includes conventionally fractionated radiotherapy over 6 weeks; however, hypofractionated radiotherapy over 3 weeks or less may be appropriate for older patients or populations with poor performance status. Lymphocyte concentration changes have been reported in patients with glioblastoma; however, monocytes are likely a key cell type contributing to immunosuppression in glioblastoma. Peripheral monocyte concentration changes in patients receiving commonly employed radiation fractionation schemes are unknown.MethodsTo determine the effect of conventionally fractionated and hypofractionated radiotherapy on complete blood cell leukocyte parameters, retrospective longitudinal concentrations were compared prior to, during, and following standard chemoradiation treatment.ResultsThis study is the first to report increased monocyte concentrations and decreased lymphocyte concentrations in patients treated with conventionally fractionated radiotherapy compared to hypofractionated radiotherapy.DiscussionUnderstanding the impact of fractionation on peripheral blood leukocytes is important to inform selection of dose fractionation schemes for patients receiving radiotherapy.

Glioblastoma (GBM) is a fatal disease, with poor prognosis exacerbated by difficulty in assessing tumor extent with imaging. Spectroscopic MRI (sMRI) is a non-contrast imaging technique measuring endogenous metabolite levels of the brain that can serve as biomarkers for tumor extension. We completed a three-site study to assess survival benefits of GBM patients when treated with escalated radiation dose guided by metabolic abnormalities in sMRI. Escalated radiation led to complex post-treatment imaging, requiring unique approaches to discern tumor progression from radiation-related treatment effect through our quantitative imaging platform. The purpose of this study is to determine true tumor recurrence timepoints for patients in our dose-escalation multisite study using novel methodology and to report on median progression-free survival (PFS). Follow-up imaging for all 30 trial patients were collected, lesion volumes segmented and graphed, and imaging uploaded to our platform for visual interpretation. Eighteen months post-enrollment, the median PFS was 16.6 months with a median time to follow-up of 20.3 months. With this new treatment paradigm, incidence rate of tumor recurrence one year from treatment is 30% compared to 60–70% failure under standard care. Based on the delayed tumor progression and improved survival, a randomized phase II trial is under development (EAF211).

Visible light communication (VLC) has emerged as a viable supplement to existing radio frequency (RF) communication systems. The limited modulation bandwidth of sources is one of the significant challenges in the multiuser (MU) VLC systems, which prohibits transmission at high data rates for each user. Since an array of LEDs is used to illuminate a room, a MU VLC system utilizing massive multiple-input multiple-output (mMIMO) orthogonal frequency-division multiplexing (OFDM) is proposed for achieving high data rates in this paper. Since the distances of the multiple transmitter-receiver links are different, their temporal delays are also different, resulting in complex channel gain and phase differences when transformed to the frequency domain in the OFDM technique. Complex channel vectors associated with different users are mutually spatially orthogonal as the number of transmitters increases. Therefore, inter-user interference (IUI) can be eliminated with simple linear signal processing, and more users can simultaneously communicate in the same time-frequency resource. In this paper, three linear precoding methods, including the maximum ratio transmission (MRT), the minimum mean square error (MMSE), and the zero-forcing (ZF), are investigated for VLC systems based on proposed MU-mMIMO-OFDM in intensity-modulation and direct-detection link. We evaluate and compare the performance of the aforementioned precoding methods in terms of the achievable spectral efficiency and total downlink optical power for different scenarios. Moreover, we derive a closed-form expression for the lower bound on the average achievable sum-rate, which we confirm the accuracy of the derived expression with the numerical simulation. The results demonstrate that the performance of the proposed method in this paper for all precoder techniques, i.e., ZF, MMSE, and MRT, is better than the previous works since the complex channel in the frequency domain is used in this paper. Furthermore, the ZF and MMSE methods are better than MRT when the ratio of the number of LEDs to the number of users is large. At the same time, when this ratio is relatively small, the MRT precoding technique outperforms the ZF and MMSE techniques.

Abstract Purpose Tumor Treating Fields (TTFields) therapy, a noninvasive, anti-mitotic treatment modality, is approved for recurrent glioblastoma (rGBM) and newly diagnosed GBM based on phase III, EF-11 (NCT00379470) and EF-14 (NCT00916409) studies, respectively. The EF-19 study aimed to evaluate efficacy and safety of TTFields monotherapy (200 kHz) vs physicians’ choice standard of care (PC-SOC; EF-11 historical control group) in rGBM. Methods A prospective, post-marketing registry study of adults with supratentorial rGBM treated with TTFields therapy was conducted. Primary endpoint was overall survival (OS; intent-to-treat [ITT] population) and secondary endpoint was OS per-protocol (PP). Subgroup and toxicity analyses were conducted. Results Median OS (ITT population) was comparable with TTFields monotherapy vs PC-SOC (7.4 vs 6.4 months, log-rank test P = 0.053; Cox test hazard ratio [HR] [95% CI], 0.66 [0.47–0.92], P = 0.016). The upper-bound HR (95% CI) was lower than pre-defined noninferiority (1.375 threshold). In the PP population, median OS was significantly longer for TTFields monotherapy vs PC-SOC (8.1 vs 6.4 months; log-rank test P = 0.017; Cox test HR [95% CI], 0.60 [0.42–0.85], P = 0.004). TTFields therapy showed increased benefit with extended use (≥ 18 h/day [averaged over 28 days]). TTFields therapy-related adverse events (AEs) by body system were lower vs PC-SOC: mainly mild-to-moderate skin AEs. Conclusion In the real-world setting, TTFields monotherapy showed comparable (ITT population) and superior (PP population) OS vs PC-SOC in rGBM. In line with previous results, TTFields therapy showed a favorable safety profile vs chemotherapy, without new safety signals/systemic effects. Trial registration: NCT01756729, registered December 20, 2012. Graphical Abstract

Abstract Introduction Healthcare facilities adopted restrictive visitor policies as a result of the COVID‐19 (COVID) pandemic. Though these measures were necessary to promote the safety of patients, families and healthcare providers, it led to isolation and loneliness amongst acute care inpatients that can undermine patient rehabilitation and recovery. The study objectives were to (1) explore how infection prevention and control (IP&C) measures impacted stakeholders' perceptions of care quality and interactions with others and (2) investigate how these experiences and perceptions varied across stakeholder groups and care settings. Methods A qualitative descriptive study was conducted. Patients and their families from an inpatient COVID rehabilitation hospital and healthcare providers from an acute or rehabilitation COVID hospital were interviewed between August 2020 and February 2021. Results A total of 10 patients, 5 family members and 12 healthcare providers were interviewed. Four major themes were identified: (1) IP&C measures challenged the psychosocial health of all stakeholders across care settings; (2): IP&C measures precipitated a need for greater relational care from HCPs; (3) infection prevention tenets perpetuated COVID‐related stigma that stakeholders experienced across care settings; and (4) technology was used to facilitate human connection when IP&C limited physical presence. Conclusion IP&C measures challenged psychosocial health and maintenance of vital human connections. Loneliness and isolation were felt by all stakeholders due to physical distancing and COVID‐related stigma. Some isolation was mitigated by the relational care provided by HCPs and technological innovations used. The findings of the study underscore the need to balance safety with psychosocial well‐being across care settings and beyond the patient–provider dyad. Patient and Public Contribution This study was informed by the Patient‐Oriented Research Agenda and developed through consultations with patients and family caregivers to identify priority areas for rehabilitation research. Priority areas identified that informed the current study were (1) the need to focus on the psychosocial aspects of recovery from illness and injury and (2) the importance of exploring patients' recovery experiences and needs across the continuum of care. The study protocol, ethics submission, analysis and manuscript preparation were all informed by healthcare providers with lived experience of working in COVID care settings.

Abstract Background The timing of events in the management of osteosarcoma may be critical for patient survivorship; however, the prognostic value of factors such as onset of symptoms or initiation of therapy in these patients has not been studied. This study sought to review the literature reporting treatment of osteosarcoma to determine the utility of event timing as a prognostic indicator. Due to significant heterogeneity in the literature, this study was conducted as a scoping review to assess the current state of the literature, identify strengths and weaknesses in current reporting practices, and to propose avenues for future improvement. Main body This review screened 312 peer-reviewed studies of osteosarcoma in any anatomic location published in an English journal for reporting of an event timing metric of any kind in a population of 6 or more. Thirty-seven studies met inclusion/exclusion criteria and were assessed for level of evidence, quality, and event timing metric. Reviewers also collated: publication year, population size, population age, tumor site, tumor type, surgical treatment, and adjuvant medical treatment. Extracted event timing data were further characterized using nine standardized categories to enable systematic analysis. The reporting of event timing in the treatment of osteosarcoma was incomplete and heterogenous. Only 37 of 312 (11.9%) screened studies reported event timing in any capacity. The period between patient-reported symptom initiation and definitive diagnosis was the most reported (17/37, 45.9%). Symptom duration was the second most reported period (10/37, 27.0%). Event timing was typically reported incidentally and was never rigorously incorporated into data analysis or discussion. No studies considered the impact of event timing on a primary outcome. The six largest studies were assessed in detail to identify pearls for future researchers. Notable shortcomings included the inadequate reporting of the definition of an event timing period and the pooling of patients into poorly defined timing groups. Conclusions Inconsistent reporting of event timing in osteosarcoma treatment prevents the development of clinically useful conclusions despite evidence to suggest event timing is a useful prognostic indicator. Consensus guidelines are necessary to improve uniformity and utility in the reporting of event timing.

Abstract Mode‐division multiplexing (MDM) using few‐mode fibre (FMF) has received increasing attention to address the exponential growth of data traffic in long‐haul optical communication systems. Also, combining the MDM with wavelength‐division multiplexing (WDM) is a promising approach for dramatically growing the transmission capacity in such systems. However, a major barrier in this regard is the FMF nonlinear effects, which can significantly reduce the link performance. In this paper, in order to alleviate the FMF nonlinear effects, we focus on power allocation in FMF links by optimizing the input power of each optical WDM channel of each spatial mode, which leads to maximizing the total capacity transmission and also the minimum signal to noise ratio (SNR) margin. The FMF nonlinearity has been already modelled as the Gaussian noise (GN) for which no closed‐form formulation has been developed so far. Here, we derive a closed‐form GN model for this problem and verify it by comparing with the integral‐form GN model and split‐step Fourier method. In this approach, an optimal power is independently determined for each channel of each mode by optimizing a capacity maximization and a minimum SNR margin maximization problem in convex forms. The performance of different links including the single mode fibre‐WDM, MDM‐single channel, and MDM‐WDM are compared using computer simulations. These systems are comprehensively investigated in equal/non‐equal required SNR as well as flat/non‐flat amplifier gain scenarios. It is shown that optimized power allocation to each channel of each mode has a significant enhancement in the minimum SNR margin maximization scheme compared to the best equal power allocation. Furthermore, this improvement is much more in non‐equal required SNR and the non‐flat amplifier gain scenarios, showing the efficiency of the established approach in practical communication links.

Purpose: To develop the safest possible environment for treating urgent patients with COVID-19 requiring radiation, we describe the unique construction of negative air pressure computed tomography simulator and linear accelerator treatment vaults in addition to screening, delay, and treatment protocols and their evolution over the course of the COVID-19 pandemic. Methods and Materials: Construction of large high-efficiency particulate air filter air-flow systems into existing ductwork in computed tomography simulator rooms and photon and proton treatment vaults was completed to create negative-pressure rooms. An asymptomatic COVID-19 screening protocol was implemented for all patients before initiation of treatment. Patients could undergo simulation and/or treatment in the biocontainment environments according to a predefined priority scale and protocol. Patients treated under the COVID-19 protocol from June 2020 to January 2022 were retrospectively reviewed. Results: Negative air-flow environments were created across a regional network, including a multi-gantry proton therapy unit. In total, 6525 patients were treated from June 2020 through January 2022 across 5 separate centers. The majority of patients with COVID-19 had radiation treatment deferred when deemed safe. A total of 42 patients with COVID-19, who were at highest risk of an adverse outcome should there be a radiation delay, were treated under the COVID-19 biocontainment protocol in contrast to those who were placed on treatment break. For 61.9% of patients, these safety measures mitigated an extended break during treatment. The majority of patients (64.3%) were treated with curative intent. The median number of biocontainment sessions required by each patient was 6 (range, 1-15) before COVID-19 clearance and resumption of treatment in a normal air-flow environment. Conclusions: Constructing negative-pressure environments and developing a COVID-19 biocontainment treatment protocol allowed for the safe treatment of urgent radiation oncology patients with COVID-19 within our department and strengthens future biopreparedness. These biocontainment units set a high standard of safety in radiation oncology during the current or for any future infectious outbreak.

Abstract Background To determine patient and surgical factors associated with the use of 360-degree laser retinopexy during primary pars plana vitrectomy (PPV) ± scleral buckle (SB) for rhegmatogenous retinal detachment (RRD) and its impact on surgical outcomes. Methods Patients who underwent PPV ± SB for repair of non-complex RRD at a single centre were included in this retrospective study. The primary outcome was single surgery anatomical success (SSAS). Secondary outcomes included visual acuity, epiretinal membrane formation, the presence of cystoid macular oedema, tonic pupil and corneal epithelial defects. Multiple logistic regression and multivariate regression was used. Results The study included 192 cases, of which 130 received 360-degree laser. Worse preoperative logMAR visual acuity (P = 0.009), male sex (P = 0.060), higher PVR grades, supplemental SB (P = 0.0468) and silicone oil/C3F8 tamponade (P 0.9999) or corneal epithelial defects (P = N/A) were found. Conclusions 360-degree laser retinopexy during primary PPV ± SB for RRD was associated with more complex cases and more extensive operations. Even when accounting for this, there was no difference in surgical outcomes or complication rates.

Glioblastoma (GBM) is highly aggressive and has a poor prognosis. Belinostat is a histone deacetylase inhibitor with blood–brain barrier permeability, anti-GBM activity, and the potential to enhance chemoradiation. The purpose of this clinical trial was to assess the efficacy of combining belinostat with standard-of-care therapy. Thirteen patients were enrolled in each of control and belinostat cohorts. The belinostat cohort was given a belinostat regimen (500–750 mg/m2 1×/day × 5 days) every three weeks (weeks 0, 3, and 6 of RT). All patients received temozolomide and radiation therapy (RT). RT margins of 5–10 mm were added to generate clinical tumor volumes and 3 mm added to create planning target volumes. Median overall survival (OS) was 15.8 months for the control cohort and 18.5 months for the belinostat cohort (p = 0.53). The recurrence volumes (rGTVs) for the control cohort occurred in areas that received higher radiation doses than that in the belinostat cohort. For those belinostat patients who experienced out-of-field recurrence, tumors were detectable by spectroscopic MRI before RT. Recurrence analysis suggests better in-field control with belinostat. This study highlights the potential of belinostat as a synergistic therapeutic agent for GBM. It may be particularly beneficial to combine this radio-sensitizing effect with spectroscopic MRI-guided RT.

The primary purpose of this study is to evaluate the role of vanity in its longstanding theoretical association with narcissism. This is particularly germane, as the conceptualization and measurement of narcissism have evolved in recent years. This is observed in the development of spectrum and/or dimensional models of narcissism, concomitant with the conceptual developments of vanity that have emerged since its original inclusion in the Narcissism Personality Inventory. Specifically, our research question evaluated whether vanity remains as traditionally construed, i.e., as a facet of narcissism, or is better conceptualized as a distinct construct separated from the earlier models of narcissism and therefore provide novel implications in understanding personality and social behavior. Based on the traits of pride, empathy, and several social behavior variables, it was hypothesized that a differentiation between narcissism and vanity would be observed. The participants were 441 undergraduate students from a large public midwestern university who participated in a self-report online survey. Correlation and regression analyses were conducted. The results revealed that the characterization of vanity is limited to pride and an absence of empathy and social behavior. Findings reaffirm behavior patterns of grandiose and vulnerable narcissism regarding selflessness, image management, and sensitivity to others. The core motivations of vanity are explicated as based on social comparison theory to assess one’s subjective and/or objective value though it is not characterized as a “social” trait or by social behavior, in contrast to how narcissism is characterized. Based on our findings and an improved understanding of the narcissism model, we conclude that vanity is more closely related to the grandiose dimension of narcissism and discuss how the underlying motivations of vanity improve our understanding of grandiose narcissism. We discuss the implications that these findings provide to the developing, modern conceptualizations of narcissism and affirm and expand our understanding of vanity in personality.

Achieving reliable communication over different wavelength channels and modes is one of the main goals of Mode Division Multiplexing-Wavelength Division Multiplexing (MDM-WDM) transmission. The reliability can be described by the minimum Signal to Noise Ratio (SNR) margin which depends on launch power, the gain of Few-Mode Erbium-Doped Fiber Amplifiers (FM-EDFA), and the nonlinear impairments of Few-Mode Fiber (FMF). In this paper, we develop the Enhanced Gaussian Noise (EGN) nonlinear model for FMF, which can be used in both weak and strong coupling regimes. We validate the model by comparing simulation results with those obtained through the Split-Step Fourier Method. Based on our proposed EGN model, we address the problem of joint optimized power and gain allocation based on minimum SNR margin maximization when accounting for practical FM-EDFA constraints such as saturation power and maximum gain. The problem is solved using a convex optimization approach and considering different scenarios such as the best equal power, optimized power, and joint optimized power and gain. Results demonstrate that the minimum SNR margin improvement for the joint optimized power and gain allocation compared to the best equal power allocation is $1.4~dB$ and $1.7~dB$ for MDM-single channel and single-mode fiber-WDM systems, respectively.

Grating couplers (GCs) are important for light to couple between optical fibers and photonic integrated circuits (PICs). The Bound State in Continuum (BIC) waveguides offer new functionalities for PIC. High-Q resonators, electro-optical modulator, and photodetectors can be built on it without etching steps. Due to the special waveguide geometry of BIC waveguides, a high efficiency GC is still missing. In this work, we demonstrated a subwavelength grating (SWG) GC for BIC waveguide with a coupling efficiency of 8 dB and a 1 dB bandwidth >70 nm. The device shows ultra-broadband behavior which is extremely useful for BIC-based PICs.

Analytical expressions for scaling of brain wave spectra derived from the general non-linear wave Hamiltonian form show excellent agreement with experimental “neuronal avalanche” data. The theory of the weakly evanescent non-linear brain wave dynamics reveals the underlying collective processes hidden behind the phenomenological statistical description of the neuronal avalanches and connects together the whole range of brain activity states, from oscillatory wave-like modes, to neuronal avalanches, to incoherent spiking, showing that the neuronal avalanches are just the manifestation of the different non-linear side of wave processes abundant in cortical tissue. In a more broad way these results show that a system of wave modes interacting through all possible combinations of the third order non-linear terms described by a general wave Hamiltonian necessarily produces anharmonic wave modes with temporal and spatial scaling properties that follow scale free power laws. To the best of our knowledge this has never been reported in the physical literature and may be applicable to many physical systems that involve wave processes and not just to neuronal avalanches.

Introduction. Surgical excisions of upper and lower extremity malignancies are increasing annually, due in part to the rising incidence of sarcomas. The purpose of this study is to compare readmissions, reoperation rate, and complications following surgical excision of soft/connective tissue vs bone malignancies of the upper and lower extremities. Methods. The Nationwide Readmissions Database (NRD) was queried from 2016-2017 to conduct a retrospective analysis of 16,435 patients diagnosed with malignant neoplasms of the long bone (ULLB, n = 1,433) and soft tissue (ULST, n = 2,049) of the upper limb and malignant neoplasms of the long bone (LLLB, n = 5,422) and soft tissue (LLST, n = 7,531) of the lower limb. Patients who underwent surgical excision of their neoplasms were included. Binomial multivariate logistic regression was used to compare complications, nonelective readmission rates, and reoperation rates between the two groups at 30 and 90 days. Results. Average age of the ULST group was 61.88, with 36% female. Average age of the ULLB group was 44.97, with 41.90% female. Average age of the LLST group was 60.96, with 46.90% female. Average age of the LLLB group was 43.09, with 42.60% female. The ULST group had lower odds of readmission within 30 days p=0.263, which became significant within 90 days of surgery p=0.045. The LLST group had significantly higher odds of infection, reoperation within 30 to 90 days of the index surgery compared to the LLLB group p

Introduction and Objectives:. Unlike conventional dorsal spinal cord stimulation (SCS)—which uses single pulses at a fixed rate—burst SCS uses a fixed-rate, five-pulse stimuli cluster as a treatment for chronic pain; mechanistic explanations suggest burst SCS differentially modulate the medial and lateral pain pathways vs conventional SCS. Neural activation differences between burst and conventional SCS are quantifiable with the spinal-evoked compound action potential (ECAP), an electrical measure of synchronous neural activation. Methods:. We implanted 7 sheep with a dorsal stimulation lead at T9/T10, a dorsal ECAP sensing lead at T6/T7, and a lead also at T9/T10 but adjacent to the anterolateral system (ALS). Both burst and conventional SCS with stimulation amplitudes up to the visual motor threshold (vMT) were delivered to 3 different dorsal spinal locations, and ECAP thresholds (ECAPTs) were calculated for all combinations. Then, changes in ALS activation were assessed with both types of SCS. Results:. Evoked compound action potential thresholds and vMTs were significantly higher (P < 0.05) with conventional vs burst SCS, with no statistical difference (P > 0.05) among stimulation sites. However, the vMT−ECAPT window (a proxy for the useable therapeutic dosing range) was significantly wider (P < 0.05) with conventional vs burst SCS. No significant difference (P > 0.05) in ALS activation was noted between conventional and burst SCS. Conclusion:. When dosed equivalently, no differentially unique change in ALS activation results with burst SCS vs conventional SCS; in addition, sub-ECAPT burst SCS results in no discernable excitability changes in the neural pathways feeding pain relevant supraspinal sites.

Introduction: During the COVID-19 pandemic, discharge timelines were accelerated and patients were moved across the continuum of care, from acute to post-acute care, to relieve the strain in health system capacity. This study aimed to investigate the COVID-19 care pathway from the perspective of patients, caregivers, and healthcare providers to understand their experiences with care and recovery within and across care settings. Methods: A qualitative descriptive study. Patients and their families from an inpatient COVID-19 unit and healthcare providers from an acute or rehabilitation COVID-19 unit were interviewed. Results: A total of 27 participants were interviewed. Three major themes were identified: 1) The perceived quality and pace of COVID-19 care improved from acute care to inpatient rehabilitation; 2) Care transitions were especially distressing; and 3) Recovery from COVID-19 stagnated in the community. Conclusion: Inpatient rehabilitation was viewed as higher quality due to the slower paced care. Care transitions were distressing for stakeholders and enhanced integration between acute and rehabilitation care were suggested to improve patient handover. A lack of rehabilitation access led to recovery stagnating for patients discharged to the community. Telerehab may improve the transition to home and ensure access to adequate rehabilitation and support in the community.

Abstract Background Egg production traits are economically important in poultry breeding programs. Previous studies have shown that incorporating genomic data can increase the accuracy of genetic prediction of egg production. Our objective was to estimate the genetic and phenotypic parameters of such traits and compare the prediction accuracy of pedigree-based random regression best linear unbiased prediction (RR-PBLUP) and genomic single-step random regression BLUP (RR-ssGBLUP). Egg production was recorded on 7422 birds during 24 consecutive weeks from first egg laid. Hatch-week of birth by week of lay and week of lay by age at first egg were fitted as fixed effects and body weight as a covariate, while additive genetic and permanent environment effects were fitted as random effects, along with heterogeneous residual variances over 24 weeks of egg production. Predictions accuracies were compared based on two statistics: (1) the correlation between estimated breeding values and phenotypes divided by the square root of the trait heritability, and (2) the ratio of the variance of BLUP predictions of individual Mendelian sampling effects divided by one half of the estimate of the additive genetic variance. Results Heritability estimates along the production trajectory obtained with RR-PBLUP ranged from 0.09 to 0.22, with higher estimates for intermediate weeks. Estimates of phenotypic correlations between weekly egg production were lower than the corresponding genetic correlation estimates. Our results indicate that genetic correlations decreased over the laying period, with the highest estimate being between traits in later weeks and the lowest between early weeks and later ages. Prediction accuracies based on the correlation-based statistic ranged from 0.11 to 0.44 for RR-PBLUP and from 0.22 to 0.57 for RR-ssGBLUP using the correlation-based statistic. The ratios of the variances of BLUP predictions of Mendelian sampling effects and one half of the additive genetic variance ranged from 0.17 to 0.26 for RR-PBLUP and from 0.17 to 0.34 for RR-ssGBLUP. Although the improvement in accuracies from RR-ssGBLUP over those from RR-PBLUP was not uniform over time for either statistic, accuracies obtained with RR-ssGBLUP were generally equal to or higher than those with RR-PBLUP. Conclusions Our findings show the potential advantage of incorporating genomic data in genetic evaluation of egg production traits using random regression models, which can contribute to the genetic improvement of egg production in turkey populations.