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1.
Nature ; 614(7946): 48-53, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36725994

RESUMEN

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.

2.
N Engl J Med ; 388(12): 1067-1079, 2023 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-36867173

RESUMEN

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.).


Asunto(s)
Antidepresivos , Aripiprazol , Bupropión , Compuestos de Litio , Nortriptilina , Cambio de Tratamiento , Anciano , Humanos , Antidepresivos/efectos adversos , Antidepresivos/uso terapéutico , Aripiprazol/efectos adversos , Aripiprazol/uso terapéutico , Bupropión/efectos adversos , Bupropión/uso terapéutico , Depresión , Quimioterapia Combinada , Nortriptilina/efectos adversos , Nortriptilina/uso terapéutico , Compuestos de Litio/efectos adversos , Compuestos de Litio/uso terapéutico
3.
Proc Natl Acad Sci U S A ; 119(42): e2204135119, 2022 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-36219693

RESUMEN

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.


Asunto(s)
Efectos Tardíos de la Exposición Prenatal , Sustancia Blanca , Encéfalo/diagnóstico por imagen , Imagen de Difusión Tensora/métodos , Femenino , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Madres , Embarazo , Sustancia Blanca/diagnóstico por imagen
4.
Clin Infect Dis ; 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38442248

RESUMEN

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.

5.
Am J Geriatr Psychiatry ; 32(2): 205-219, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37798223

RESUMEN

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.


Asunto(s)
Salud Mental , Calidad de Vida , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Estudios de Factibilidad , Ansiedad/terapia , Ansiedad/psicología , Depresión/diagnóstico
6.
Artículo en Inglés | MEDLINE | ID: mdl-39209616

RESUMEN

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.

7.
Dev Sci ; 27(3): e13456, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37902111

RESUMEN

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.


Asunto(s)
Sueño , Sustancia Blanca , Recién Nacido , Lactante , Humanos , Embarazo , Femenino , Ritmo Circadiano , Encéfalo , Sustancia Gris
8.
Ultrasound Obstet Gynecol ; 64(3): 314-321, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38379440

RESUMEN

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.


Asunto(s)
Transfusión Feto-Fetal , Fetoscopía , Embarazo Gemelar , Humanos , Transfusión Feto-Fetal/cirugía , Transfusión Feto-Fetal/mortalidad , Femenino , Embarazo , Fetoscopía/métodos , Adulto , Terapia por Láser/métodos , Resultado del Tratamiento , Edad Gestacional , Resultado del Embarazo , Estudios Retrospectivos , Recién Nacido
9.
Ultrasound Obstet Gynecol ; 63(3): 371-377, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-37553800

RESUMEN

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.


Asunto(s)
Transfusión Feto-Fetal , Ginecología , Femenino , Embarazo , Humanos , Consenso , Técnica Delphi , Transfusión Feto-Fetal/diagnóstico por imagen , Transfusión Feto-Fetal/cirugía , Fetoscopía
10.
Appetite ; 193: 107124, 2024 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-37980953

RESUMEN

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.


Asunto(s)
Preferencias Alimentarias , Gusto , Masculino , Humanos , Femenino , Adulto , Alimentos , Recompensa , Carbohidratos , Ingestión de Energía
11.
Rhinology ; 62(3): 330-341, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38189480

RESUMEN

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.


Asunto(s)
Pérdida de Líquido Cefalorraquídeo , Endoscopía , Procedimientos de Cirugía Plástica , Base del Cráneo , Humanos , Femenino , Masculino , Base del Cráneo/cirugía , Pérdida de Líquido Cefalorraquídeo/etiología , Pérdida de Líquido Cefalorraquídeo/prevención & control , Pérdida de Líquido Cefalorraquídeo/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Endoscopía/métodos , Procedimientos de Cirugía Plástica/métodos , Adulto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anciano , Neoplasias Hipofisarias/cirugía , Neoplasias de la Base del Cráneo/cirugía , Rinorrea de Líquido Cefalorraquídeo/prevención & control , Rinorrea de Líquido Cefalorraquídeo/cirugía , Rinorrea de Líquido Cefalorraquídeo/etiología
12.
Biom J ; 66(6): e202300185, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39101657

RESUMEN

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.


Asunto(s)
Biometría , Personal de Salud , Análisis por Conglomerados , Funciones de Verosimilitud , Humanos , Personal de Salud/estadística & datos numéricos , Biometría/métodos , Trasplante de Riñón , Algoritmos
13.
Nat Methods ; 17(7): 717-725, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32601426

RESUMEN

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.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Luz , Optogenética , Arabidopsis/genética , Arabidopsis/inmunología , Sistemas CRISPR-Cas/genética , Modelos Teóricos , Plantas Modificadas Genéticamente
14.
New Phytol ; 237(6): 2210-2223, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36660914

RESUMEN

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.


Asunto(s)
Marchantia , Marchantia/genética , Marchantia/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Filogenia , Calcio/metabolismo , Tolerancia a la Sal/genética , Estrés Fisiológico/genética , Proteínas de Unión al Calcio/metabolismo
15.
Opt Express ; 31(9): 14185-14195, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37157288

RESUMEN

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.

16.
Opt Express ; 31(20): 31839-31852, 2023 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-37859000

RESUMEN

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.

17.
Br J Surg ; 110(4): 471-480, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-36785496

RESUMEN

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.


Asunto(s)
Neoplasias Colorrectales , Humanos , Sensibilidad y Especificidad , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Estudios Prospectivos , Hemoglobinas/análisis , Heces/química , Sangre Oculta , Detección Precoz del Cáncer/métodos , Colonoscopía
18.
Phys Rev Lett ; 131(5): 051801, 2023 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-37595210

RESUMEN

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.

19.
Phys Rev Lett ; 131(1): 011801, 2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37478458

RESUMEN

Neutrino-induced charged-current single π^{+} production in the Δ(1232) resonance region is of considerable interest to accelerator-based neutrino oscillation experiments. In this Letter, high statistic differential cross sections are reported for the semiexclusive reaction ν_{µ}A→µ^{-}π^{+}+ nucleon(s) on scintillator, carbon, water, iron, and lead targets recorded by MINERvA using a wideband ν_{µ} beam with ⟨E_{ν}⟩≈6 GeV. Suppression of the cross section at low Q^{2} and enhancement of low T_{π} are observed in both light and heavy nuclear targets compared with phenomenological models used in current neutrino interaction generators. The cross sections per nucleon for iron and lead compared with CH across the kinematic variables probed are 0.8 and 0.5 respectively, a scaling which is also not predicted by current generators.

20.
Phys Rev Lett ; 130(16): 161801, 2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37154647

RESUMEN

This Letter presents the first simultaneous measurement of the quasielasticlike neutrino-nucleus cross sections on C, water, Fe, Pb, and scintillator (hydrocarbon or CH) as a function of longitudinal and transverse muon momentum. The ratio of cross sections per nucleon between Pb and CH is always above unity and has a characteristic shape as a function of transverse muon momentum that evolves slowly as a function of longitudinal muon momentum. The ratio is constant versus longitudinal momentum within uncertainties above a longitudinal momentum of 4.5 GeV/c. The cross section ratios to CH for C, water, and Fe remain roughly constant with increasing longitudinal momentum, and the ratios between water or C to CH do not have any significant deviation from unity. Both the overall cross section level and the shape for Pb and Fe as a function of transverse muon momentum are not reproduced by current neutrino event generators. These measurements provide a direct test of nuclear effects in quasielasticlike interactions, which are major contributors to long-baseline neutrino oscillation data samples.

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