Characterizing two-mode-squeezed light from four-wave mixing in rubidium vapor for quantum sensing and information processing.

We present a study of homodyne measurements of two-mode, vacuum-seeded, quadrature-squeezed light generated by four-wave mixing in warm rubidium vapor. Our results reveal that the vacuum squeezing can extend down to measurement frequencies of less than 1 Hz, and the squeezing bandwidth, similar to the seeded intensity-difference squeezing measured in this system, reaches up to approximately 20 MHz for typical pump parameters. By dividing the squeezing bandwidth into smaller frequency bins, we show that different sideband frequencies represent independent sources of two-mode squeezing. These properties are useful for quantum sensing and quantum information processing applications. We also investigate the impact of group velocity delays on the correlations in the system, which allows us to optimize the useful spectrum.

Cognitive Behavioral Therapy for Insomnia Self-Management Mobile Apps: A Review of Efficacy and Quality.

Cognitive behavioral therapy for insomnia (CBT-I) is the recommended treatment for insomnia, yet multiple barriers limit utilization. Digital CBT-I may present a solution, though related reviews have focused on Internet-based delivery rather than app use. The high utilization of health apps and prevalence of sleep apps indicate the need to equip clinicians with app-specific research. Toward this end, we reviewed efficacy and quality data on self-management CBT-I smartphone apps, revealing efficacy research on eleven apps, five of which were publicly available. While preliminary, these efficacy studies showed consistent positive findings. When examining quantitative quality indicators for the five publicly available apps, two had consistent data. Overall, two apps, CBTi Coach and Insomnia Coach, had positive, empirical findings across all efficacy and quality assessment approaches. We provide recommendations to guide clinician decision making regarding CBT-I self-management apps based on the literature and publicly available methods of app evaluations.

Child and family perceptions of satisfaction with neutropenia management in pediatric acute myeloid leukemia.

PURPOSE: Chemotherapy for pediatric acute myeloid leukemia (AML) is very intensive and many, but not all centers, require extended hospitalization until neutrophil recovery. Child and family preferences, beliefs, and experiences around hospitalization have not been systematically assessed. PATIENTS AND METHODS: We recruited children with AML and their parents from nine pediatric cancer centers across the United States for a qualitative interview about their experiences of neutropenia management. Interviews were analyzed using a conventional content analysis approach. RESULTS: Of 116 eligible individuals, 86 (74.1%) agreed to participate. Interviews were conducted with 32 children and 54 parents from 57 families. Of these 57 families, 39 were cared for as inpatients and 18 were managed as outpatients. A very high proportion of respondents in both groups reported satisfaction with the discharge management strategy recommended by the treating institution: 86% (57 individuals) of respondents who experienced inpatient management and 85% (17 individuals) of respondents who experienced outpatient management expressed satisfaction. Respondent perceptions associated with satisfaction related to safety (access to emergency interventions, infection risk, close monitoring) and psychosocial concerns (family separation, low morale, social support). Respondents believed it could not be assumed that all children would have the same experience due to varied life circumstances. CONCLUSION: Children with AML and their parents express a very high degree of satisfaction with the discharge strategy recommended by their treating institution. Respondents saw a nuanced tradeoff between patient safety and psychosocial concerns that was mediated by a child's life circumstances.

Justification Of Empiric Methodology to Determine Dexmedetomidine Dose for the TREX Study.

INTRODUCTION: Dexmedetomidine is the sedative agent administered in combination with remifentanil and low dose of sevoflurane in the interventional arm of the ongoing TREX trial (Trial Remifentanil DExmedetomidine). The TREX pilot study (published in Paediatr Anaesth 2019;29:59-67) established infusion rates higher than those initially proposed. This could be attributed to an inappropriate target concentration for sedation or incorrect initial pharmacokinetic parameter estimates. METHODS: The TREX study is a Phase III, randomized, active controlled, parallel group, blinded evaluator, multicentre, superiority trial comparing neurological outcome after standard sevoflurane anaesthesia with dexmedetomidine/remifentanil and low dose sevoflurane anaesthesia in children aged less than 2 years undergoing anaesthesia of 2 hours or longer. In this report, dexmedetomidine pharmacokinetics were analysed in the interventional arm of the Italian population. RESULTS: There were 162 blood samples from 32 infants (22 male and 10 female). The median (IQR) age was 12 (5.2-15.5) months, weight 9.9 (7.3-10.8) kg. Duration of anaesthesia ranged from 2-6 hours. None of the children were born premature (median postnatal age 39 weeks, IQR 38-40 weeks). A 3-compartment PK model that incorporated allometric scaling and a maturation function demonstrated plasma concentration observations from the current Italian arm of the TREX study were consistent with those predicted by a "universal" model using pooled data obtained from neonates to adults. CONCLUSIONS: This current PK analysis from the Italian arm of the TREX study confirms that plasma concentration of dexmedetomidine is predictable using known covariates such as age and size. The initial target concentration (0.6 µg.L-1 ) used to sedate children cared for in the intensive care after cardiac surgery was inadequate for infants in the current TREX study. A target concentration 1 mcg.L-1 , corresponding to a loading dose of 1 mcg.kg-1 followed by an infusion of 1 mcg.kg-1 .hour-1 , provided adequate sedation.

Erratum: Azimuthal Anisotropy at the Relativistic Heavy Ion Collider: The First and Fourth Harmonics [Phys. Rev. Lett. 92, 062301 (2004)].

This corrects the article DOI: 10.1103/PhysRevLett.92.062301.

Erratum: Azimuthal Anisotropy of K_{S}

This corrects the article DOI: 10.1103/PhysRevLett.89.132301.

Outcome of patients with relapsed or progressive Ewing sarcoma enrolled on cooperative group phase 2 clinical trials: A report from the Children's Oncology Group.

SevenChildren's Oncology Group phase 2 trials for patients with relapsed/progressive solid tumors were analyzed to estimate the event-free survival (EFS) for relapsed/progressive Ewing sarcoma. One hundred twenty-eight Ewing sarcoma patients were enrolled and 124 events occurred. The 6-month EFS was 12.7%, demonstrating the poor outcome of these patients. Only docetaxel achieved its protocol-specified radiographic response rate for activity; however, the EFS for docetaxel was similar to other agents, indicating that a higher radiographic response rate may not translate into superior disease control. This EFS benchmark could be utilized as an additional endpoint in trials for recurrent Ewing sarcoma.

Impact of COVID-19 Pandemic on Timing of Childhood Cancer Diagnoses.

The COVID-19 pandemic impacted the health care system in unprecedented ways. We reviewed the registry of new cancer patients who presented to the Children's of Mississippi Center for Cancer and Blood Disorders and showed the average number of new pediatric cancer diagnoses dropped during the initial COVID-19 months and rose significantly in June 2020. We must encourage families to seek health care when needed and keep scheduled appointments for routine vaccinations and health maintenance as we know the long-term sequela of delaying health maintenance far outweighs risks at present.

First clinical experience with single-port robotic transanal minimally invasive surgery (SP rTAMIS) for benign rectal neoplasms.

BACKGROUND: The new da Vinci Single-Port (SP) robot is a single-arm four-channel robotic system well suited for endoluminal surgery. We report our initial experience performing SP robotic transanal minimally invasive surgery (SP rTAMIS) for rectal neoplasms. METHODS: Under Institutional Review Board approval, two patients with rectal neoplasms were prospectively enrolled for elective SP rTAMIS. The primary endpoint was to report the safety and feasibility of successful procedure completion with the SP robot. Secondary endpoints included patient characteristics and perioperative metrics. RESULTS: Both patients underwent successful SP rTAMIS resection of rectal neoplasms without intraoperative complications or conversions. The lesions were 4.0 cm and 3.0 cm in size, located 6 cm and 7 cm cephalad to the anorectal ring. Excisions were full thickness with no piecemeal extractions or specimen fragmentation. Estimated blood loss was 0 mL and 30 mL. The mean excised area was 13.4 cm2 (22.7 cm2 and 9.0 cm2). The mean docking time was 5.25 min (range 2-8 min) and mean console time was 122.5 min (98 min and 147 min). Patients tolerated a liquid diet on postoperative day (POD) 0 and were discharged on POD 1 after tolerating a low residue diet and having bowel function. Pathology showed two adenomas with negative margins. There was no immediate or delayed morbidity or mortality. CONCLUSIONS: Our initial experience indicates that SP rTAMIS is a safe and feasible approach for local excision of rectal lesions. While SP rTAMIS is very promising, more experience with this approach is necessary to determine its widespread applicability.

Reducing the Impacts of Mental Health Stigma Through Integrated Primary Care: An Examination of the Evidence.

The reduction of mental health stigma (MHS) was an expected benefit of integrating behavioral health in primary care (IPC). However, unlike other barriers discussed in agency reports on IPC, discussions of MHS lack research support. To fill this gap, the authors conducted a literature review identifying seven studies. Given the dearth of research, we also examine general IPC research on probable indicators of MHS reduction in IPC, as well as, facets of IPC potentially influencing MHS related factors negatively associated with help-seeking. Using the data from these three types of research, the evidence suggests the potential of IPC to reduce MHS impact on care utilization, but indicates it is premature to draw firm conclusions. Given the possible benefits of primary care and the known benefits of decreased MHS, this review highlights the importance of further research examining this question and provides specific research and program development recommendations.

Immunity to LuloHya and Lundep, the salivary spreading factors from Lutzomyia longipalpis, protects against Leishmania major infection.

Salivary components from disease vectors help arthropods to acquire blood and have been shown to enhance pathogen transmission in different model systems. Here we show that two salivary enzymes from Lutzomyia longipalpis have a synergist effect that facilitates a more efficient blood meal intake and diffusion of other sialome components. We have previously shown that Lundep, a highly active endonuclease, enhances parasite infection and prevent blood clotting by inhibiting the intrinsic pathway of coagulation. To investigate the physiological role of a salivary hyaluronidase in blood feeding we cloned and expressed a recombinant hyaluronidase from Lu. longipalpis. Recombinant hyaluronidase (LuloHya) was expressed in mammalian cells and biochemically characterized in vitro. Our study showed that expression of neutrophil CXC chemokines and colony stimulating factors were upregulated in HMVEC cells after incubation with LuloHya and Lundep. These results were confirmed by the acute hemorrhage, edema and inflammation in a dermal necrosis (dermonecrotic) assay involving a massive infiltration of leukocytes, especially neutrophils, in mice co-injected with hemorrhagic factor and these two salivary proteins. Moreover, flow cytometry results showed that LuloHya and Lundep promote neutrophil recruitment to the bite site that may serve as a vehicle for establishment of Leishmania infection. A vaccination experiment demonstrated that LuloHya and Lundep confer protective immunity against cutaneous leishmaniasis using the Lu. longipalpis-Leishmania major combination as a model. Animals (C57BL/6) immunized with LuloHya or Lundep showed minimal skin damage while lesions in control animals remained ulcerated. This protective immunity was abrogated when B-cell-deficient mice were used indicating that antibodies against both proteins play a significant role for disease protection. Rabbit-raised anti-LuloHya antibodies completely abrogated hyaluronidase activity in vitro. Moreover, in vivo experiments demonstrated that blocking LuloHya with specific antibodies interferes with sand fly blood feeding. This work highlights the relevance of vector salivary components in blood feeding and parasite transmission and further suggests the inclusion of these salivary proteins as components for an anti-Leishmania vaccine.

Molecular mechanisms of acclimation to long-term elevated temperature exposure in marine symbioses.

Seawater temperature rise in French Polynesia has repeatedly resulted in the bleaching of corals and giant clams. Because giant clams possess distinctive ectosymbiotic features, they represent a unique and powerful model for comparing molecular pathways involved in (a) maintenance of symbiosis and (b) acquisition of thermotolerance among coral reef organisms. Herein, we explored the physiological and transcriptomic responses of the clam hosts and their photosynthetically active symbionts over a 65 day experiment in which clams were exposed to either normal or environmentally relevant elevated seawater temperatures. Additionally, we used metabarcoding data coupled with in situ sampling/survey data to explore the relative importance of holobiont adaptation (i.e., a symbiont community shift) versus acclimation (i.e., physiological changes at the molecular level) in the clams' responses to environmental change. We finally compared transcriptomic data to publicly available genomic datasets for Symbiodiniaceae dinoflagellates (both cultured and in hospite with the coral Pocillopora damicornis) to better tease apart the responses of both hosts and specific symbiont genotypes in this mutualistic association. Gene module preservation analysis revealed that the function of the symbionts' photosystem II was impaired at high temperature, and this response was also found across all holobionts and Symbiodiniaceae lineages examined. Similarly, epigenetic modulation appeared to be a key response mechanism for symbionts in hospite with giant clams exposed to high temperatures, and such modulation was able to distinguish thermotolerant from thermosensitive Cladocopium goreaui ecotypes; epigenetic processes may, then, represent a promising research avenue for those interested in coral reef conservation in this era of changing global climate.

Time spent outside of target glucose range for young children with type 1 diabetes: a continuous glucose monitor study.

AIM: To assess the associations between demographic and clinical characteristics and sensor glucose metrics in young children with type 1 diabetes, using masked, continuous glucose monitoring data from children aged 2 to < 8 years. RESEARCH DESIGN AND METHODS: The analysis included 143 children across 14 sites in the USA, enrolled in a separate clinical trial. Eligibility criteria were: age 2 to <8 years; type 1 diabetes duration ≥3 months; no continuous glucose monitoring use for past 30 days; and HbA1c concentration 53 to <86 mmol/mol (7.0 to <10.0%). All participants wore masked continuous glucose monitors up to 14 days. RESULTS: On average, participants spent the majority (13 h) of the day in hyperglycaemia (>10.0 mmol/l) and a median of ~1 h/day in hypoglycaemia (<3.9 mmol/l). Participants with minority race/ethnicity and higher parent education levels spent more time in target range, 3.9-10.0 mmol/l, and less time in hyperglycaemia. More time in hypoglycaemia was associated with minority race/ethnicity and younger age at diagnosis. Continuous glucose monitoring metrics were similar in pump and injection users. CONCLUSIONS: Given that both hypo- and hyperglycaemia negatively impact neurocognitive development, strategies to increase time in target glucose range for young children are needed.

Single-Institution Experience of Synovial Sarcoma.

OBJECTIVES: The purpose of this study was to investigate the patient population and outcomes of synovial sarcoma at a single institution. METHODS: A retrospective review of the medical records of 28 patients with synovial sarcoma diagnosed from 1992 to 2017 was performed. Demographics, staging, disease location, treatment, and response to treatment were reviewed. RESULTS: Individuals with larger tumors at the time of presentation had an increased risk of death. An additional factor associated with poor prognosis in synovial sarcoma was increasing patient age. The patient population had a higher rate of nonextremity disease and lower overall survival when compared with national averages. CONCLUSIONS: Nonextremity disease and large size of tumor at presentation may have contributed to the disparity in institutional outcomes from the national averages. The advanced presentation of synovial sarcoma remains a significant challenge in improving patient survival.

Single-port robotic left colectomy: first clinical experience using the SP robot (rSILS).

BACKGROUND: The single-port daVinci robot is a new platform designed to facilitate single-incision surgeries. The objective of this study was to describe the first clinical experience in colorectal surgery using a novel single-port robotic system and report its feasibility and safety. METHODS: After Institutional Review Board approval was obtained and the study was registered with ClinicalTrials.gov, we performed single port robot-assisted left colectomy using the novel daVinci SP surgical system on two patients. The surgeries were completed through a single incision. The multichannel port accommodates a three-dimensional articulating camera and three double-jointed articulating instruments. The primary aim of this study was to report, for the first time in the USA, the technical feasibility of the procedure in the living human. The secondary aim was to report the outcomes including blood loss, number of incisions, number of dockings, docking time of the robot, incision length, operative time, console time, need for additional port and instrumentation, intraoperative complications, morbidity and mortality, time for tolerating diet, bowel function, and discharge. RESULTS: Both surgeries were completed without conversion through a single incision, 4.0 and 4.5 cm in size. Estimated blood loss was less than 60 ml in both cases. The robot was docked two and three times. Mean time to dock was 13 min (range 3-33 min). There were no intraoperative complications, no morbidity or death. Discharges occurred on postoperative days 2 and 3. CONCLUSIONS: Single-port robotic colectomy using the new robot is feasible and can be safely completed. The overall utility and functionality of the SP robot portends wide utilization and expansion of this technique. Careful development and analysis of the procedure outcomes, training, and cost will be necessary to properly advance the field.

Value-driven attentional capture is modulated by the contents of working memory: An EEG study.

Attention and working memory (WM) have previously been shown to interact closely when sensory information is being maintained. However, when non-sensory information is maintained in WM, the relationship between WM and sensory attention may be less strong. In the current study, we used electroencephalography to evaluate whether value-driven attentional capture (i.e., allocation of attention to a task-irrelevant feature previously associated with a reward) and its effects on either sensory or non-sensory WM performance might be greater than the effects of salient, non-reward-associated stimuli. In a training phase, 19 participants learned to associate a color with reward. Then, participants were presented with squares and encoded their locations into WM. Participants were instructed to convert the spatial locations either to another type of sensory representation or to an abstract, relational type of representation. During the WM delay period, task-irrelevant distractors, either previously-rewarded or non-rewarded, were presented, with a novel color distractor in the other hemifield. The results revealed lower alpha power and larger N2pc amplitude over posterior electrode sides contralateral to the previously rewarded color, compared to ipsilateral. These effects were mainly found during relational WM, compared to sensory WM, and only for the previously rewarded distractor color, compared to a previous non-rewarded target color or novel color. These effects were associated with modulations of WM performance. These results appear to reflect less capture of attention during maintenance of specific location information, and suggest that value-driven attentional capture can be mitigated as a function of the type of information maintained in WM.

Relation of reproductive disturbance in sheep and Leptospira interrogans serovar Icterohaemorrhagiae infection: Impacts on cellular oxidation status.

This study evaluated the seropositivity of Brucella abortus and Leptospira interrogans in ewes with reproductive disturbances in southern Brazil and verified the creatine kinase (CK) activity and oxidation status via assessment of superoxide dismutase, glutathione peroxidase and glutathione transferase in serum of seropositive animals for L. interrogans serovar Icterohaemorrhagiae. For Leptospira infection 381 animals with clinical history of reproductive disturbance from Planalto Serrano de Santa Catarina (Brazil) were analyzed, showing an occurrence for L. interrogans of 20.2% from which 81.8% were seropositive for L. interrogans Icterohaemorrhagiae. Serovars Wolfii, Grippothyphosa, Bratislava, Canicola and Butembo were also identified. In the case of B. abortus, positive cases were identified by buffered acidified antigen, finding 14 positive samples, but none of them were positive after a second test (2-mercaptoethanol), showing the absence of relationship between infection with B. abortus and abortion in the tested individuals. Serum reactive oxygen species (ROS) levels and CK activity were found higher in animals positive for Leptospira infection, presenting higher titrations (1:320) than non-infected individuals. Serum glutathione peroxidase activity was higher in positive animals with titrations 1:160 and 1:320, while serum glutathione S-transferase was higher in positive individuals only for titrations 1:320. Serum superoxide dismutase showed lower activity in infected animals with titrations of 1:320. Our results show the region of Planalto Serrano de Santa Catarina with a high occurrence levels of sheep infected by L. interrogans serovar Icterohaemorrhagiae, from which animals with high titrations (1:320) present oxidative stress elicited by excessive ROS production, triggering the stimulation of antioxidant systems to counter this excess. In summary, ovine with higher titrations (1:320) present oxidative damage that can contribute to disease pathophysiology.

Text-message responsiveness to blood glucose monitoring reminders is associated with HbA1c benefit in teenagers with Type 1 diabetes.

AIMS: To evaluate an 18-month text-messaging intervention in teenagers with Type 1 diabetes and to assess factors associated with text responsiveness and glycaemic benefit. METHODS: Teenagers with diabetes (N = 147), aged 13-17 years, received two-way text reminders at self-selected times to check blood glucose levels and reply with blood glucose results. RESULTS: At baseline, the participants (48% boys, 78% white, 63% pump-treated) had a mean ± sd age of 14.9 ± 1.3 years, diabetes duration of 7.1 ± 3.9 years and HbA1c concentration of 69 ± 12 mmol/mol (8.5 ± 1.1%). The mean proportion of days with ≥1 blood glucose response declined over time (0-6 months, 60 ± 26% of days, 7-12 months, 53 ± 31% of days, 13-18 months, 43 ± 33% of days). Over 18 months, 49% responded with ≥1 blood glucose result on ≥50% of days (high responders). Regression analysis controlling for baseline HbA1c revealed no significant change in HbA1c from baseline to 18 months in high responders (P = 0.54) compared with a significant HbA1c increase in low responders (+0.3%, P = 0.01). In participants with baseline HbA1c ≥64 mmol/mol (≥8%), high responders were 2.5 times more likely than low responders to have a clinically significant [≥5.5 mmol/mol (≥0.5%)] HbA1c decrease over 18 months (P < 0.05). In participants with baseline HbA1c <64 mmol/mol(<8%), high responders were 5.7 times more likely than low responders to have an 18-month HbA1c <58 mmol/mol (<7.5%; P < 0.05). CONCLUSIONS: Teenagers with Type 1 diabetes who responded to text reminders on ≥50% of days over 18 months experienced clinically significant glycaemic benefit. There remains a need to tailor interventions to maintain teenager engagement and optimize improvements.

Inflammatory profiling of patients with familial amyloid polyneuropathy.

BACKGROUND: Familial amyloid polyneuropathy (FAP) or ATTRv (amyloid TTR variant) amyloidosis is a fatal hereditary disease characterized by the deposition of amyloid fibrils composed of transthyretin (TTR). The current diagnosis of ATTRv relies on genetic identification of TTR mutations and on Congo Red-positive amyloid deposits, which are absent in most ATTRv patients that are asymptomatic or early symptomatic, supporting the need for novel biomarkers to identify patients in earlier disease phases allowing disease control. METHODS: In an effort to search for new markers for ATTRv, our group searched for nine inflammation markers in ATTRv serum from a cohort of 28 Brazilian ATTRv patients. RESULTS: We found that the levels of six markers were increased (TNF-α, IL-1ß, IL-8, IL-33, IFN-ß and IL-10), one had decreased levels (IL-12) and two of them were unchanged (IL-6 and cortisol). Interestingly, asymptomatic patients already presented high levels of IL-33, IL-1ß and IL-10, suggesting that inflammation may take place before fibril deposition. CONCLUSIONS: Our findings shed light on a new, previously unidentified aspect of ATTRv, which might help define new criteria for disease management, as well as provide additional understanding of ATTRv aggressiveness.

EMIC Waves in the Outer Magnetosphere: Observations of an Off-Equator Source Region.

Electromagnetic ion cyclotron (EMIC) waves at large L shells were observed away from the magnetic equator by the Magnetospheric MultiScale (MMS) mission nearly continuously for over four hours on 28 October 2015. During this event, the wave Poynting vector direction systematically changed from parallel to the magnetic field (toward the equator), to bidirectional, to antiparallel (away from the equator). These changes coincide with the shift in the location of the minimum in the magnetic field in the southern hemisphere from poleward to equatorward of MMS. The local plasma conditions measured with the EMIC waves also suggest that the outer magnetospheric region sampled during this event was generally unstable to EMIC wave growth. Together, these observations indicate that the bidirectionally propagating wave packets were not a result of reflection at high latitudes but that MMS passed through an off-equator EMIC wave source region associated with the local minimum in the magnetic field.