Measurement of the axial vector form factor from antineutrino-proton scattering.

Scattering of high energy particles from nucleons probes their structure, as was done in the experiments that established the non-zero size of the proton using electron beams1. The use of charged leptons as scattering probes enables measuring the distribution of electric charges, which is encoded in the vector form factors of the nucleon2. Scattering weakly interacting neutrinos gives the opportunity to measure both vector and axial vector form factors of the nucleon, providing an additional, complementary probe of their structure. The nucleon transition axial form factor, FA, can be measured from neutrino scattering from free nucleons, νµn → µ-p and [Formula: see text], as a function of the negative four-momentum transfer squared (Q2). Up to now, FA(Q2) has been extracted from the bound nucleons in neutrino-deuterium scattering3-9, which requires uncertain nuclear corrections10. Here we report the first high-statistics measurement, to our knowledge, of the [Formula: see text] cross-section from the hydrogen atom, using the plastic scintillator target of the MINERvA11 experiment, extracting FA from free proton targets and measuring the nucleon axial charge radius, rA, to be 0.73 ± 0.17 fm. The antineutrino-hydrogen scattering presented here can access the axial form factor without the need for nuclear theory corrections, and enables direct comparisons with the increasingly precise lattice quantum chromodynamics computations12-15. Finally, the tools developed for this analysis and the result presented are substantial advancements in our capabilities to understand the nucleon structure in the weak sector, and also help the current and future neutrino oscillation experiments16-20 to better constrain neutrino interaction models.

Antidepressant Augmentation versus Switch in Treatment-Resistant Geriatric Depression.

BACKGROUND: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. METHODS: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:1 ratio to augmentation of existing antidepressant medication with aripiprazole, augmentation with bupropion, or a switch from existing antidepressant medication to bupropion. Patients who did not benefit from or were ineligible for step 1 were randomly assigned in step 2 in a 1:1 ratio to augmentation with lithium or a switch to nortriptyline. Each step lasted approximately 10 weeks. The primary outcome was the change from baseline in psychological well-being, assessed with the National Institutes of Health Toolbox Positive Affect and General Life Satisfaction subscales (population mean, 50; higher scores indicate greater well-being). A secondary outcome was remission of depression. RESULTS: In step 1, a total of 619 patients were enrolled; 211 were assigned to aripiprazole augmentation, 206 to bupropion augmentation, and 202 to a switch to bupropion. Well-being scores improved by 4.83 points, 4.33 points, and 2.04 points, respectively. The difference between the aripiprazole-augmentation group and the switch-to-bupropion group was 2.79 points (95% CI, 0.56 to 5.02; P = 0.014, with a prespecified threshold P value of 0.017); the between-group differences were not significant for aripiprazole augmentation versus bupropion augmentation or for bupropion augmentation versus a switch to bupropion. Remission occurred in 28.9% of patients in the aripiprazole-augmentation group, 28.2% in the bupropion-augmentation group, and 19.3% in the switch-to-bupropion group. The rate of falls was highest with bupropion augmentation. In step 2, a total of 248 patients were enrolled; 127 were assigned to lithium augmentation and 121 to a switch to nortriptyline. Well-being scores improved by 3.17 points and 2.18 points, respectively (difference, 0.99; 95% CI, -1.92 to 3.91). Remission occurred in 18.9% of patients in the lithium-augmentation group and 21.5% in the switch-to-nortriptyline group; rates of falling were similar in the two groups. CONCLUSIONS: In older adults with treatment-resistant depression, augmentation of existing antidepressants with aripiprazole improved well-being significantly more over 10 weeks than a switch to bupropion and was associated with a numerically higher incidence of remission. Among patients in whom augmentation or a switch to bupropion failed, changes in well-being and the occurrence of remission with lithium augmentation or a switch to nortriptyline were similar. (Funded by the Patient-Centered Outcomes Research Institute; OPTIMUM ClinicalTrials.gov number, NCT02960763.).

Prenatal exposure to maternal social disadvantage and psychosocial stress and neonatal white matter connectivity at birth.

Early life adversity (social disadvantage and psychosocial stressors) is associated with altered microstructure in fronto-limbic pathways important for socioemotional development. Understanding when these associations begin to emerge may inform the timing and design of preventative interventions. In this longitudinal study, 399 mothers were oversampled for low income and completed social background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent factors: social disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, and nutrition) and psychosocial stress (depression, stress, life events, and racial discrimination). At birth, 289 healthy term-born neonates underwent a diffusion MRI (dMRI) scan. Mean diffusivity (MD) and fractional anisotropy (FA) were measured for the dorsal and inferior cingulum bundle (CB), uncinate, and fornix using probabilistic tractography in FSL. Social disadvantage and psychosocial stress were fitted to dMRI parameters using regression models adjusted for infant postmenstrual age at scan and sex. Social disadvantage, but not psychosocial stress, was independently associated with lower MD in the bilateral inferior CB and left uncinate, right fornix, and lower MD and higher FA in the right dorsal CB. Results persisted after accounting for maternal medical morbidities and prenatal drug exposure. In moderation analysis, psychosocial stress was associated with lower MD in the left inferior CB among the lower-to-higher socioeconomic status (SES) (INR ≥ 200%) group, but not the extremely low SES (INR < 200%) group. Increasing access to social welfare programs that reduce the burden of social disadvantage and related psychosocial stressors may be an important target to protect fetal brain development in fronto-limbic pathways.

Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM).

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by experts in both adult and pediatric laboratory and clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including arboviral Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also addressed. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

A Perioperative Mental Health Intervention for Depressed and Anxious Older Surgical Patients: Results From a Feasibility Study.

OBJECTIVES: The perioperative period is challenging and stressful for older adults. Those with depression and/or anxiety have an increased risk of adverse surgical outcomes. We assessed the feasibility of a perioperative mental health intervention composed of medication optimization and a wellness program following principles of behavioral activation and care coordination for older surgical patients. METHODS: We included orthopedic, oncologic, and cardiac surgical patients aged 60 and older. Feasibility outcomes included study reach, the number of patients who agreed to participate out of the total eligible; and intervention reach, the number of patients who completed the intervention out of patients who agreed to participate. Intervention efficacy was assessed using the Patient Health Questionnaire for Anxiety and Depression (PHQ-ADS). Implementation potential and experiences were collected using patient surveys and qualitative interviews. Complementary caregiver feedback was also collected. RESULTS: Twenty-three out of 28 eligible older adults participated in this study (mean age 68.0 years, 65% women), achieving study reach of 82% and intervention reach of 83%. In qualitative interviews, patients (n = 15) and caregivers (complementary data, n = 5) described overwhelmingly positive experiences with both the intervention components and the interventionist, and reported improvement in managing depression and/or anxiety. Preliminary efficacy analysis indicated improvement in PHQ-ADS scores (F = 12.13, p <0.001). CONCLUSIONS: The study procedures were reported by participants as feasible and the perioperative mental health intervention to reduce anxiety and depression in older surgical patients showed strong implementation potential. Preliminary data suggest its efficacy for improving depression and/or anxiety symptoms. A randomized controlled trial assessing the intervention and implementation effectiveness is currently ongoing.

Poor Sleep is Common in Treatment-Resistant Late-life Depression and Associated With Poorer Antidepressant Response: Findings From the OPTIMUM Clinical Trial.

BACKGROUND: Adults with treatment-resistant late-life depression (TRLLD) have high rates of sleep problems; however, little is known about the occurrence and change in sleep during pharmacotherapy of TRLLD. This analysis examined: (1) the occurrence of insufficient sleep among adults with TRLLD; (2) how sleep changed during pharmacotherapy; and (3) whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep. METHODS: Secondary analysis of data from 634 participants age 60+ years in the OPTIMUM clinical trial for TRLLD. Sleep was assessed using the sleep item from the Montgomery-Asberg Depression Rating Scale at the beginning (week-0) and end (week-10) of treatment. The analyses examined whether treatment outcomes differed among participants with persistent insufficient sleep, worsened sleep, improved sleep, or persistent sufficient sleep during depression treatment. RESULTS: About half (51%, n = 323) of participants reported insufficient sleep at baseline. Both persistent insufficient sleep (25%, n = 158) and worsened sleep (10%, n = 62) during treatment were associated with antidepressant nonresponse. Participants who maintained sufficient sleep (26%, n = 164) or who improved their sleep (n = 25%, n = 158) were three times more likely to experience a depression response than those with persistent insufficient sleep or worsened sleep. CONCLUSION: Insufficient sleep is common in TRLLD and it is associated with poorer treatment response to antidepressants.

The Cognitive Profile of Older Adults With Treatment-Resistant Depression: An Analysis of the OPTIMUM Randomized Controlled Trial.

OBJECTIVE: Major depressive disorder in older adults (late-life depression; LLD) is frequently associated with cognitive impairment, and some deficits (e.g., executive function) have been associated with a higher level of treatment resistance. However, the cognitive profile of treatment-resistant LLD (TR-LLD) has not been characterized. We hypothesized that patients with TR-LLD would show deficits in cognitive function, especially executive function, and that executive function deficits would predict poorer response to pharmacotherapy. DESIGN: Secondary analysis of baseline cognitive data from OPTIMUM, a multicenter RCT evaluating pharmacotherapy strategies for TR-LLD. SETTING: Five outpatient academic medical centers (4 US, 1 Canada). PARTICIPANTS: About 369 participants aged 60 and older from the OPTIMUM study. MEASUREMENTS: Baseline scores on individual tasks and composite scores from the NIH Toolbox-Cognition Battery were transformed into demographically-adjusted T-scores and compared to published norms. Impairments in the set shifting and inhibitory control tasks were investigated as predictors of depressive symptom change following treatment using ANCOVA models. RESULTS: Participants had low performance on tasks evaluating inhibitory control, processing speed, verbal/nonverbal memory, and the fluid composite, but normative performance on working memory and set shifting. Participants had high estimated premorbid IQ (superior Performance on oral reading recognition). Age and physical comorbidity negatively associated with processing speed. Impairments in set shifting predicted less improvement in depressive symptoms; impairments in inhibitory control did not. CONCLUSIONS: Participants with TR-LLD presented with broad cognitive deficits relative to healthy norms. Given poorer outcomes following standard pharmacotherapy associated with impaired set shifting, future research needs to identify alternative treatment strategies.

Sleep and circadian rhythms during pregnancy, social disadvantage, and alterations in brain development in neonates.

Pregnant women in poverty may be especially likely to experience sleep and circadian rhythm disturbances, which may have downstream effects on fetal neurodevelopment. However, the associations between sleep and circadian rhythm disturbances, social disadvantage during pregnancy, and neonatal brain structure remains poorly understood. The current study explored the association between maternal sleep and circadian rhythm disturbances during pregnancy and neonatal brain outcomes, examining sleep and circadian rhythm disturbances as a mediator of the effect of social disadvantage during pregnancy on infant structural brain outcomes. The study included 148 mother-infant dyads, recruited during early pregnancy, who had both actigraphy and neuroimaging data. Mothers' sleep was assessed throughout their pregnancy using actigraphy, and neonates underwent brain magnetic resonance imaging in the first weeks of life. Neonatal structural brain outcomes included cortical gray matter, subcortical gray matter, and white matter volumes along with a measure of the total surface area of the cortex. Neonates of mothers who experienced greater inter-daily deviations in sleep duration had smaller total cortical gray and white matter volumes and reduced cortical surface areas. Neonates of mothers who had higher levels of circadian misalignment and later sleep timing during pregnancy showed smaller subcortical gray matter volumes. Inter-daily deviations in sleep duration during pregnancy mediated the association between maternal social disadvantage and neonatal structural brain outcomes. Findings highlight the importance of regularity and rhythmicity in sleep schedules during pregnancy and bring to light the role of chronodisruption as a potential mechanism underlying the deleterious neurodevelopmental effects of prenatal adversity. RESEARCH HIGHLIGHTS: Social disadvantage was associated with sleep and circadian rhythm disturbances during pregnancy, including later sleep schedules, increased variability in sleep duration, circadian misalignment, and a higher proportion of the sleep period spent awake. Maternal sleep and circadian rhythm disturbances during pregnancy were associated with decreased brain volume and reduced cortical surface area in neonates. Maternal inter-daily deviations in sleep duration during pregnancy mediated the association between social disadvantage and neonatal brain volume and cortical surface area.

Stage-based recipient and donor outcome in twin-to-twin transfusion syndrome treated by fetoscopic laser surgery using Solomon technique.

OBJECTIVE: To evaluate twin survival stratified by Quintero stage in patients with twin-to-twin transfusion syndrome (TTTS) after Solomon laser treatment. METHODS: This was a single-center study at Johns Hopkins Center for Fetal Therapy, investigating a cohort of consecutive twin pregnancies treated with the Solomon laser technique for TTTS. Preoperative Quintero stage, perioperative characteristics and obstetric factors were investigated in relation to neonatal survival of the recipient and donor twins at discharge. Determinants of twin survival were evaluated using univariate logistic regression and cumulative survival probability analyses. RESULTS: Of 402 pregnancies with TTTS that underwent Solomon laser treatment, 80 (19.9%) were diagnosed with Quintero Stage-I TTTS, 126 (31.3%) with Stage II, 169 (42.0%) with Stage III and 27 (6.7%) with Stage IV. Post-laser twin anemia polycythemia sequence or recurrent TTTS occurred in 19 (4.7%) patients and 11 (2.7%) required repeat laser surgery. Preterm prelabor rupture of membranes occurred in 150 (37.3%) patients and median gestational age at delivery was 32 + 1 weeks. In 303 (75.4%) patients, both twins were alive at discharge; 67/80 (83.8%) were Stage I, 101/126 (80.2%) were Stage II, 113/169 (66.9%) were Stage III and 22/27 (81.5%) were Stage IV (P = 0.062). Donor twin survival was lower than that of recipients in cases with Stage-III TTTS (118/169 (69.8%) vs 145/169 (85.8%) (χ2 = 26.076, P < 0.0001)). Higher intertwin size discordance and absent or reversed umbilical artery (UA) end-diastolic velocity (EDV) were associated with donor demise (Nagelkerke R2, 0.38; P < 0.001). Overall, spontaneous post-laser donor demise occurred in 53 (39.6%) patients, accounting for the majority of all losses. Cumulative donor survival decreased from 92% to 65% when intertwin size discordance was >30% and to 48% when UA-EDV was absent or reversed (P < 0.001). CONCLUSIONS: The Solomon laser technique achieves TTTS resolution and double twin survival in a high proportion of cases. Recipient and donor survival is comparable unless there is significant intertwin size discordance and placental dysfunction. This degree of unequal placental sharing, typically found in Stage-III TTTS, is the primary factor preventing double survival due to a higher rate of donor demise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Consensus protocol for management of early and late twin-twin transfusion syndrome: Delphi study.

OBJECTIVE: Fetoscopic laser photocoagulation (FLP) is a well-established treatment for twin-twin transfusion syndrome (TTTS) between 16 and 26 weeks' gestation. High-quality evidence and guidelines regarding the optimal clinical management of very early (prior to 16 weeks), early (between 16 and 18 weeks) and late (after 26 weeks) TTTS are lacking. The aim of this study was to construct a structured expert-based clinical consensus for the management of early and late TTTS. METHODS: A Delphi procedure was conducted among an international panel of experts. Participants were chosen based on their clinical expertise, affiliation and relevant publications. A four-round Delphi survey was conducted using an online platform and responses were collected anonymously. In the first round, a core group of experts was asked to answer open-ended questions regarding the indications, timing and modes of treatment for early and late TTTS. In the second and third rounds, participants were asked to grade each statement on a Likert scale (1, completely disagree; 5, completely agree) and to add any suggestions or modifications. At the end of each round, the median score for each statement was calculated. Statements with a median grade of 5 without suggestions for change were accepted as the consensus. Statements with a median grade of 3 or less were excluded from the Delphi process. Statements with a median grade of 4 were modified according to suggestions and reconsidered in the next round. In the last round, participants were asked to agree or disagree with the statements, and those with more than 70% agreement without suggestions for change were considered the consensus. RESULTS: A total of 122 experts met the inclusion criteria and were invited to participate, of whom 53 (43.4%) agreed to take part in the study. Of those, 75.5% completed all four rounds. A consensus on the optimal management of early and late TTTS was obtained. FLP can be offered as early as 15 weeks' gestation for selected cases, and can be considered up to 28 weeks. Between 16 and 18 weeks, management should be tailored according to Doppler findings. CONCLUSIONS: A consensus-based treatment protocol for early and late TTTS was agreed upon by a panel of experts. This protocol should be modified at the discretion of the operator, according to their experience and the specific demands of each case. This should advance the quality of future studies, guide clinical practice and improve patient care. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Evidence that carbohydrate-to-fat ratio and taste, but not energy density or NOVA level of processing, are determinants of food liking and food reward.

This virtual (online) study tested the common but largely untested assumptions that food energy density, level of processing (NOVA categories), and carbohydrate-to-fat (CF) ratio are key determinants of food reward. Individual participants (224 women and men, mean age 35 y, 53% with healthy weight, 43% with overweight or obesity) were randomised to one of three, within-subjects, study arms: energy density (32 foods), or level of processing (24 foods), or CF ratio (24 foods). They rated the foods for taste pleasantness (liking), desire to eat (food reward), and sweetness, saltiness, and flavour intensity (for analysis averaged as taste intensity). Against our hypotheses, there was not a positive relationship between liking or food reward and either energy density or level of processing. As hypothesised, foods combining more equal energy amounts of carbohydrate and fat (combo foods), and foods tasting more intense, scored higher on both liking and food reward. Further results were that CF ratio, taste intensity, and food fibre content (negatively), independent of energy density, accounted for 56% and 43% of the variance in liking and food reward, respectively. We interpret the results for CF ratio and fibre in terms of food energy-to-satiety ratio (ESR), where ESR for combo foods is high, and ESR for high-fibre foods is low. We suggest that the metric of ESR should be considered when designing future studies of effects of food composition on food reward, preference, and intake.

Does stage III rectal mucinous adenocarcinoma benefit from neoadjuvant chemoradiation?

BACKGROUND: This study aimed to compare clinical outcomes of patients with clinical stage III mucinous rectal adenocarcinoma (M) and non-mucinous rectal adenocarcinoma (NM) and evaluate the effectiveness of neoadjuvant chemoradiation. It was hypothesized that patients with M would fare worse with neoadjuvant chemoradiation than those with NM and that patients with M and NM not receiving chemoradiation would have similar outcomes. Moreover, it was hypothesized that patients with M would have similar outcomes regardless of chemoradiation. METHODS: This study compares eligible patients distributed in three cohorts: (cohort 1) M versus NM, including only patients treated with neoadjuvant chemoradiation; (cohort 2) M versus NM, including only patients treated without neoadjuvant chemoradiation; and (cohort 3) only M patients treated with versus without neoadjuvant chemoradiation. RESULTS: We identified 515 patients with an average age of 58.8 (SD 12.4) years, and 30% were female. Fifty-seven (11.1%) patients had M and 458 (88.9%) had NM. Neoadjuvant chemoradiation was administered to 382 (74%) patients, of whom 41 (10.7%) were M and 341 (89.3%) NM. In cohort 1, patients with M had advanced pathological staging (stage 3: M 68% vs. NM 42%; p < 0.001), worse pathological differentiation (poor: M, 37% vs. NM, 11%; p = 0.001), more involved lymph nodes (M 0 [0;7] vs. NM 0 [0;1]; p < 0.001) and a higher rate of local recurrence (M 22% vs. 3%; p < 0.001). Patients with M demonstrated worse 7-year cancer-specific (p = 0.007) and overall survival (p = 0.01). There were no significant differences in cohort 2 and 3. CONCLUSION: Patients with clinical stage III mucinous adenocarcinomas may not benefit as much from standard neoadjuvant chemoradiation as their non-mucinous counterparts do.

Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

Health Care Provider Clustering Using Fusion Penalty in Quasi-Likelihood.

There has been growing research interest in developing methodology to evaluate the health care providers' performance with respect to a patient outcome. Random and fixed effects models are traditionally used for such a purpose. We propose a new method, using a fusion penalty to cluster health care providers based on quasi-likelihood. Without any priori knowledge of grouping information, our method provides a desirable data-driven approach for automatically clustering health care providers into different groups based on their performance. Further, the quasi-likelihood is more flexible and robust than the regular likelihood in that no distributional assumption is needed. An efficient alternating direction method of multipliers algorithm is developed to implement the proposed method. We show that the proposed method enjoys the oracle properties; namely, it performs as well as if the true group structure were known in advance. The consistency and asymptotic normality of the estimators are established. Simulation studies and analysis of the national kidney transplant registry data demonstrate the utility and validity of our method.

Optogenetic control of gene expression in plants in the presence of ambient white light.

Optogenetics is the genetic approach for controlling cellular processes with light. It provides spatiotemporal, quantitative and reversible control over biological signaling and metabolic processes, overcoming limitations of chemically inducible systems. However, optogenetics lags in plant research because ambient light required for growth leads to undesired system activation. We solved this issue by developing plant usable light-switch elements (PULSE), an optogenetic tool for reversibly controlling gene expression in plants under ambient light. PULSE combines a blue-light-regulated repressor with a red-light-inducible switch. Gene expression is only activated under red light and remains inactive under white light or in darkness. Supported by a quantitative mathematical model, we characterized PULSE in protoplasts and achieved high induction rates, and we combined it with CRISPR-Cas9-based technologies to target synthetic signaling and developmental pathways. We applied PULSE to control immune responses in plant leaves and generated Arabidopsis transgenic plants. PULSE opens broad experimental avenues in plant research and biotechnology.

CIPK-B is essential for salt stress signalling in Marchantia polymorpha.

Calcium signalling is central to many plant processes, with families of calcium decoder proteins having expanded across the green lineage and redundancy existing between decoders. The liverwort Marchantia polymorpha has fast become a new model plant, but the calcium decoders that exist in this species remain unclear. We performed phylogenetic analyses to identify the calcineurin B-like (CBL) and CBL-interacting protein kinase (CIPK) network of M. polymorpha. We analysed CBL-CIPK expression during salt stress, and determined protein-protein interactions using yeast two-hybrid and bimolecular fluorescence complementation. We also created genetic knockouts using CRISPR/Cas9. We confirm that M. polymorpha has two CIPKs and three CBLs. Both CIPKs and one CBL show pronounced salt-responsive transcriptional changes. All M. polymorpha CBL-CIPKs interact with each other in planta. Knocking out CIPK-B causes increased sensitivity to salt, suggesting that this CIPK is involved in salt signalling. We have identified CBL-CIPKs that form part of a salt tolerance pathway in M. polymorpha. Phylogeny and interaction studies imply that these CBL-CIPKs form an evolutionarily conserved salt overly sensitive pathway. Hence, salt responses may be some of the early functions of CBL-CIPK networks and increased abiotic stress tolerance required for land plant emergence.

Scanning mirror based higher order Bessel-gaussian beams integrated in time (HOBBIT) with applications toward the photoacoustic effect.

We demonstrate a new method for the generation of beams with rapidly tunable orbital angular momentum (OAM). This method is based on using a single-axis scanning galvanometer mirror to add a phase tilt on an elliptical Gaussian beam that is then wrapped to a ring using optics that perform a log-polar transformation. This system can switch between modes in the kHz range and use relatively high power with high efficiency. This scanning mirror HOBBIT system was applied to a light/matter interaction application using the photoacoustic effect, with a 10 dB enhancement of the generated acoustics at a glass/water interface.

High data-rate communication link supported through the exploitation of optical channels in a characterized turbulent underwater environment.

Underwater turbulence presents a myriad of challenges for underwater optical systems through wavefront distortion and beam deflection. In this work, an underwater turbulence emulator is developed and thoroughly characterized to experimentally test the proposed underwater turbulence mitigation technique. This technique applies a modified HOBBIT system introduced in atmospheric turbulence to the relatively unknown underwater turbulence domain. By varying a beam's spatial position and relative phase gradient, a volume of turbulence is rapidly probed to determine the beam state for optimal propagation. This probe and control method is applied in multiple facets, including improved optical power transmission as well as supporting a 25-Gbps communication link through a dynamic environment.

Double faecal immunochemical testing in patients with symptoms suspicious of colorectal cancer.

BACKGROUND: Faecal immunochemical test (FIT)-directed pathways based on a single test have been implemented for symptomatic patients. However, with a single test, the sensitivity is 87 per cent at 10 µg haemoglobin (Hb) per g faeces. This aims of this study were to define the diagnostic performance of a single FIT, compared with double FIT in symptomatic populations. METHODS: Two sequential prospective patient cohorts referred with symptoms from primary care were studied. Patients in cohort 1 were sent a single FIT, and those in cohort 2 received two tests in succession before investigation. All patients were investigated, regardless of having a positive or negative test (threshold 10 µg Hb per g). RESULTS: In cohort 1, 2260 patients completed one FIT and investigation. The sensitivity of single FIT was 84.1 (95 per cent c.i. 73.3 to 91.8) per cent for colorectal cancer and 67.4 (61.0 to 73.4) per cent for significant bowel pathology. In cohort 2, 3426 patients completed at least one FIT, and 2637 completed both FITs and investigation. The sensitivity of double FIT was 96.6 (90.4 to 99.3) per cent for colorectal cancer and 83.0 (77.4 to 87.8) per cent for significant bowel pathology. The second FIT resulted in a 50.0 per cent reduction in cancers missed by the first FIT, and 30.0 per cent for significant bowel pathology. Correlation between faecal Hb level was only modest (rs = 0.58), and 16.8 per cent of double tests were discordant, 11.4 per cent in patients with colorectal cancer and 18.3 per cent in those with significant bowel pathology. CONCLUSION: FIT in patients with high-risk symptoms twice in succession reduces missed significant colorectal pathology and has an acceptable workload impact.

Neutrino-Induced Coherent π

MINERvA has measured the ν_{µ}-induced coherent π^{+} cross section simultaneously in hydrocarbon (CH), graphite (C), iron (Fe), and lead (Pb) targets using neutrinos from 2 to 20 GeV. The measurements exceed the predictions of the Rein-Sehgal and Berger-Sehgal PCAC based models at multi-GeV ν_{µ} energies and at produced π^{+} energies and angles, E_{π}>1 GeV and θ_{π}<10°. Measurements of the cross-section ratios of Fe and Pb relative to CH reveal the effective A scaling to increase from an approximate A^{1/3} scaling at few GeV to an A^{2/3} scaling for E_{ν}>10 GeV.