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A deep-seated Pseudomonas aeruginosa mouse kidney abscess model was used to compare the therapeutic efficacy of clinafloxacin, a fluoroquinolone in clinical trials, with that of clinically relevant standard drugs. Following 50 mg/kg oral doses, twice daily for five consecutive days, clinafloxacin produced a 4 log decrease in mean bacterial count, the greatest decrease of all drugs tested. The same dosage regimen resulted in complete bacterial eradication in 88% of the kidneys. No other compound produced total bacterial clearance in 50% of the kidneys at the highest dose tested. [ABSTRACT FROM PUBLISHER]

Abstract Hoxa9 is a homeodomain transcription factor important for the generation of Flt3+hiIL-7R- lymphoid biased-multipotential progenitors, Flt3+IL-7R+ common lymphoid progenitors (CLPs), and B cell precursors (BCP) in bone marrow (BM). In addition to B-cell, Flt3+IL-7R+ CLPs possess NK and DC developmental potentials, although DCs arise from Flt3+IL-7R- myeloid progenitors as well. In this study, we investigated the requirement for Hoxa9, from Flt3+ or Flt3- progenitor subsets, in the development of NK and DC lineage cells in BM. Flt3+IL-7R+Ly6D- CLPs and their Flt3+IL-7R+Ly6D+ B lineage-restricted progeny (BLP) were significantly reduced in hoxa9−/− mice. Interestingly, the reduction in Flt3+IL-7R+ CLPs in hoxa9−/− mice had no impact on the generation of NK precursor (NKP) subsets, the differentiation of NKP into mature NK cells, or NK homeostasis. Similarly, percentages and numbers of common dendritic progenitors (CDP), as well as their plasmacytoid or conventional dendritic cell progeny in hoxa9−/− mice were comparable to wildtype. These findings reveal distinct requirements for Hoxa9 or Hoxa9/Flt3 molecular circuits in regulation of B versus NK and DC development in BM.

Abstract Background The transient receptor potential vanilloid type1 (TRPV1) is expressed in nociceptive sensory neurons and is sensitive to phosphorylation. A-Kinase Anchoring Protein 79/150 (AKAP150) mediates phosphorylation of TRPV1 by Protein Kinases A and C, modulating channel activity. However, few studies have focused on the regulatory mechanisms that control AKAP150 association with TRPV1. In the present study, we identify a role for calcium/calmodulin in controlling AKAP150 association with, and sensitization of, TRPV1. Results In trigeminal neurons, intracellular accumulation of calcium reduced AKAP150 association with TRPV1 in a manner sensitive to calmodulin antagonism. This was also observed in transfected Chinese hamster ovary (CHO) cells, providing a model for conducting molecular analysis of the association. In CHO cells, the deletion of the C-terminal calmodulin-binding site of TRPV1 resulted in greater association with AKAP150, and increased channel activity. Furthermore, the co-expression of wild-type calmodulin in CHOs significantly reduced TRPV1 association with AKAP150, as evidenced by total internal reflective fluorescence-fluorescence resonance energy transfer (TIRF-FRET) analysis and electrophysiology. Finally, dominant-negative calmodulin co-expression increased TRPV1 association with AKAP150 and increased basal and PKA-sensitized channel activity. Conclusions the results from these studies indicate that calcium/calmodulin interferes with the association of AKAP150 with TRPV1, potentially extending resensitization of the channel.

Abstract Background The Morris water maze task is a hippocampus-dependent learning and memory test that typically takes between 3 days to 2 weeks of training. This task is used to assess spatial learning and induces the expression of genes known to be crucial to learning and memory in the hippocampus. A major caveat in the protocol is the prolonged duration of training, and difficulty of assessing the time during training in which animals have learned the task. We introduce here a condensed version of the task that like traditional water maze tasks, creates lasting hippocampus-dependent spatial cognitive maps and elicits gene expression following learning. Methods This paradigm was designed for rats to quickly acquire a hippocampus-dependent spatial cognitive map and retain this memory for at least 24 hours. To accomplish this, we interspersed visible and hidden training trials, delivering them in a massed fashion so training takes a maximum of 15 minutes. Learning was assessed based on latencies to the platform during each training trial, as well as time spent in the goal quadrant during probe testing 30 minutes and 24 hours after training. Normal rats were compared to two impaired cohorts (rats with fimbria-fornix lesions and rats administered NMDA receptor antagonist (CPP)). To quantitate hippocampal expression of known learning genes, real-time polymerase chain reaction (RT-PCR) was performed on hippocampal cDNA. Results We show that massed training using alternating visible and hidden training trials generates robust short-term working and long-term reference memories in rats. Like the traditional Morris water maze paradigm, this task requires proper hippocampal function, as rats with fimbria-fornix lesions and rats administered CPP fail to learn the spatial component of the task. Furthermore, training in this paradigm elicits hippocampal expression of genes upregulated following learning in a variety of spatial tasks: homer1a, cfos and zif268. Conclusions We introduce here a condensed version of the Morris water maze, which is like a traditional water maze paradigm, in that it is hippocampus-dependent, and elicits hippocampal expression of learning genes. However, this task is administered in 15 minutes and induces spatial memory for at least 24 hours.

Abstract Background In 2003, the National Institute of Mental Health funded the Child and Adolescent Psychiatry Trials Network (CAPTN) under the Advanced Center for Services and Intervention Research (ACSIR) mechanism. At the time, CAPTN was believed to be both a highly innovative undertaking and a highly speculative one. One reviewer even suggested that CAPTN was "unlikely to succeed, but would be a valuable learning experience for the field." Objective To describe valuable lessons learned in building a clinical research network in pediatric psychiatry, including innovations intended to decrease barriers to research participation. Methods The CAPTN Team has completed construction of the CAPTN network infrastructure, conducted a large, multi-center psychometric study of a novel adverse event reporting tool, and initiated a large antidepressant safety registry and linked pharmacogenomic study focused on severe adverse events. Specific challenges overcome included establishing structures for network organization and governance; recruiting over 150 active CAPTN participants and 15 child psychiatry training programs; developing and implementing procedures for site contracts, regulatory compliance, indemnification and malpractice coverage, human subjects protection training and IRB approval; and constructing an innovative electronic casa report form (eCRF) running on a web-based electronic data capture system; and, finally, establishing procedures for audit trail oversight requirements put forward by, among others, the Food and Drug Administration (FDA). Conclusion Given stable funding for network construction and maintenance, our experience demonstrates that judicious use of web-based technologies for profiling investigators, investigator training, and capturing clinical trials data, when coupled to innovative approaches to network governance, data management and site management, can reduce the costs and burden and improve the feasibility of incorporating clinical research into routine clinical practice. Having successfully achieved its initial aim of constructing a network infrastructure, CAPTN is now a capable platform for large safety registries, pharmacogenetic studies, and randomized practical clinical trials in pediatric psychiatry.

A 110 GHz quasi-optical ring resonator, designed for use with a 1 MW pulsed gyrotron, has been built and successfully tested using a 100 mW solid-state source. A low reflectance (2.4%) input coupler and a low-loss, four-mirror ring demonstrated a compression ratio, defined as the ratio of output to input power, of 36. The 6 ns output pulses were generated from the 2 m length ring using a silicon laser-driven semiconductor switch (LDSS). The quasi-optical ring resonator was designed with large waist sizes so that input pulses of up to 1 MW will stay under the 35 kV/cm electric field limit for ionization in ambient air. Maximum compression gain was achieved by matching the input coupling fraction to the round trip loss in the ring, achieving close to critical coupling. The experimental output pulse shape obtained after firing the LDSS was modeled using the reflectance, transmittance, and absorptance of the switch vs. time and vs. laser pulse fluence, with good agreement found with theory. The timing for the peak energy efficiency of 32% was found and the main loss mechanism limiting that efficiency was found to be the absorptance in the silicon wafer., Competing Interests: Conflict of Interest The authors declare no competing interests.

We present 3D electromagnetic simulations of the coupling of a 250 GHz beam to the sample in a 380 MHz DNP NMR spectrometer. To obtain accurate results for magic angle spinning (MAS) geometries, we first measured the complex dielectric constants of zirconia, sapphire, and the sample matrix material (DNP juice) from room temperature down to cryogenic temperatures and from 220 to 325 GHz with a VNA and up to 1 THz with a THz TDS system. Simulations of the coupling to the sample were carried out with the ANSYS HFSS code as a function of the rotor wall material (zirconia or sapphire), the rotor wall thickness, and the THz beam focusing (lens or no lens). For a zirconia rotor, the B 1 field in the sample was found to be strongly dependent on the rotor wall thickness, which is attributed to the high refractive index of zirconia. The optimum thickness of the wall is likely due to a transmission maximum but is offset from the thickness predicted by a simple calculation for a flat slab of the wall material. The B 1 value was found to be larger for a sapphire rotor than for a zirconia rotor for all cases studied. The results found in this work provide new insights into the coupling of THz radiation to the sample and should lead to improved designs of future DNP NMR instrumentation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The xCures platform aggregates, organizes, structures, and normalizes clinical EMR data across care sites, utilizing advanced technologies for near real-time access. The platform generates data in a format to support clinical care, accelerate research, and promote artificial intelligence/ machine learning algorithm development, highlighted by a clinical decision support algorithm for precision oncology., Competing Interests: Acknowledgments: Soma Sengupta and Rohan Rao have no conflicts of interest to report. All other authors have employment and equity interest in xCures., (Copyright ©2024 by the North Carolina Institute of Medicine and The Duke Endowment. All rights reserved.)

In the fall of 2019, a much-publicized court case brought to national attention the issues of patient-doctor confidentiality when it comes to reporting the deaths of newborns in the United States. It is unclear whether the recent overturning of Roe v. Wade will lead to more cases like this. This article discusses issues of countertransference, as well as the ethical and legal implications were it to be a psychiatrist, in active treatment of such a patient, who would be required to make such a report. More specifically, as in the publicized court case, the patient could be a minor at the time, receiving treatment from a child psychiatrist. The implications of such a case include how countertransference affects the perception of fatal child neglect compared to intentional neonaticide; the ethical dilemma of generating a mandated report with the goal of child safety when such a report could lead to real legal consequences for a minor child; and considerations regarding continued treatment of a patient after such a report is made. It is likely that countertransference, shaped by attitudes toward mothers and idealized views on mothering, may play a large role in all these circumstances.

Over 160 therapeutic and in vivo diagnostic monoclonal antibodies have been approved by the US FDA since the first monoclonal antibody, muromonab, was approved in 1986. Approximately 42% of these approvals were for the treatment or in vivo diagnosis of oncology indications, although some products are no longer marketed. This review will look at the history of monoclonal antibody development and approvals, discuss current antibody-based modalities, regulatory considerations for engineering approaches, critical quality attributes for different modalities, immunogenicity of mAbs across oncology products, and the future directions for development of therapeutic and diagnostic monoclonal antibody-based products., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shapiro.)

Introduction: Exceptional response to therapy is rare in patients with advanced pancreatic cancer. This study explored potential genomic differences between typical and exceptional responses that could confer more favorable biology., Methods: We included exceptional responders and controls with advanced pancreatic cancer from Cleveland Clinic from April 2013 to August 2017. Exceptional responders were defined as patients with an overall survival of more than 18 months for metastatic disease and more than 24 months for locally advanced disease. Clinical data were obtained, and next-generation sequencing was performed. Statistical analyses comparing the 2 groups were performed using descriptive statistics, the Kaplan-Meier method, and the log-rank test., Results: The study comprised 4 exceptional responders and 6 controls. Both groups were well balanced in age, sex, race, and treatment regimens. Exceptional responders had significantly fewer nonsynonymous mutations than controls (2.25 vs 5.17; P = .014). A mutation count of less than 3 was associated with significantly better progression-free survival (17.2 vs 2.3 months; P = .002) and overall survival (29.4 vs 4.6 months; P = .013). Tumor mutational burden did not differ between exceptional responders and controls (4.88 vs 5.70 mut/Mb; P = .39)., Conclusion: A lower number of nonsynonymous mutations may correlate with exceptional outcomes in patients with pancreatic cancer. These findings should encourage future studies into genomic signatures of exceptional response.

Introduction: Innovative strategies are needed in clinical education to teach empathetic behavior and communication skills. This study aimed to investigate preclinical medical students' experiences volunteering as abortion doulas and to understand the impact of their participation on their professional training., Methods: In this qualitative study, the authors conducted semistructured interviews with medical students who had volunteered as abortion doulas in March to July 2016. The interviews described motivations for participating, experiences volunteering as a doula, approach to caring for patients, and acquisition of communication skills and knowledge of abortion. The authors analyzed interview transcripts using a conventional content analysis approach, and themes were identified., Results: The authors performed 22 interviews. For most participants, this was their first exposure to an abortion procedure or patient care in any capacity. Participants identified acquisition of skills including patient advocacy, communication, and empathy that they were later able to apply throughout their clinical clerkships. This opportunity improved well-being and solidified their decision to apply for residencies in reproductive health fields., Discussion: After volunteering as abortion doulas, medical students were able to develop communication skills, empathy, and patient advocacy applicable to other areas of patient care. Preclinical students, potentially in other health care professions training, participating in patient care as doulas have the potential to further personal development, professionalism, and activism., (© 2023 The Authors. Journal of Midwifery & Women's Health published by Wiley Periodicals LLC on behalf of American College of Nurse Midwives (ACNM).)

The reflectance ( R ) and transmittance ( T ) of Si and GaAs wafers irradiated by a 6 ns pulsed, 532 nm laser have been studied for s- and p-polarized 250 GHz radiation as a function of laser fluence and time. The measurements were carried out using precision timing of the R and T signals, allowing an accurate determination of the absorptance ( A ) where A = 1 - R - T . Both wafers had a maximum reflectance above 90% for a laser fluence ≥ 8  mJ / cm 2 . Both also showed an absorptance peak of ~50% lasting ~2 ns during the risetime of the laser pulse. Experimental results were compared with a stratified medium theory using the Vogel model for the carrier lifetime and the Drude model for permittivity. Modeling showed that the large absorptance at the early part of the rise of the laser pulse was due to the creation of a lossy, low carrier density layer. For Si, the measured R ,   T and A were in very good agreement with theory on both the nanosecond time scale and the microsecond scale. For GaAs, the agreement was very good on the nanosecond scale but only qualitatively correct on the microsecond scale. These results may be useful for planning applications of laser driven semiconductor switches.

Viral diseases represent a major public health concerns and ever-present risks for developing into future pandemics. Antiviral antibody therapeutics, either alone or in combination with other therapies, emerged as valuable preventative and treatment options, including during global emergencies. Here we will discuss polyclonal and monoclonal antiviral antibody therapies, focusing on the unique biochemical and physiological properties that make them well-suited as therapeutic agents. We will describe the methods of antibody characterization and potency assessment throughout development, highlighting similarities and differences between polyclonal and monoclonal products as appropriate. In addition, we will consider the benefits and challenges of antiviral antibodies when used in combination with other antibodies or other types of antiviral therapeutics. Lastly, we will discuss novel approaches to the characterization and development of antiviral antibodies and identify areas that would benefit from additional research.

The systematic monitoring of private communications through the use of information technology pervades the digital age. One result of this is the potential availability of vast amount of data tracking the characteristics of mobile network users. Such data is becoming increasingly accessible for commercial use, while the accessibility of such data raises questions about the degree to which personal information can be protected. Existing regulations may require the removal of personally-identifiable information (PII) from datasets before they can be processed, but research now suggests that powerful machine learning classification methods are capable of targeting individuals for personalized marketing purposes, even in the absence of PII. This study aims to demonstrate how machine learning methods can be deployed to extract demographic characteristics. Specifically, we investigate whether key demographics-gender and age-of mobile users can be accurately identified by third parties using deep learning techniques based solely on observations of the user's interactions within the network. Using an anonymized dataset from a Latin American country, we show the relative ease by which PII in terms of the age and gender demographics can be inferred; specifically, our neural networks model generates an estimate for gender with an accuracy rate of 67%, outperforming decision tree, random forest, and gradient boosting models by a significant margin. Neural networks achieve an even higher accuracy rate of 78% in predicting the subscriber age. These results suggest the need for a more robust regulatory framework governing the collection of personal data to safeguard users from predatory practices motivated by fraudulent intentions, prejudices, or consumer manipulation. We discuss in particular how advances in machine learning have chiseled away a number of General Data Protection Regulation (GDPR) articles designed to protect consumers from the imminent threat of privacy violations., Competing Interests: The authors have declared that no competing interests exist.

Objective: The introduction of the Milestone Project underscored the need for objective assessments of resident progress across the competencies. Therefore, the authors examined the Psychiatry Resident-In-Training Examination (PRITE) utility for measuring improvements in medical knowledge (MK)., Methods: The authors compared the mean performance for each MK subcompetency by resident year for all residents taking the PRITE from 2015 to 2017 (18,175 examination administrations). In addition, they surveyed psychiatry residency program directors regarding how well they thought they teach these subcompetencies., Results: Increases in MK subcompetencies by resident year were significant for Psychopathology (p < 0.003), Psychotherapy (p < 0.002), and Somatic Therapies (p < 0.000). Development, Clinical Neuroscience, and Practice of Psychiatry did not show statistically significant differences between postgraduate years. Eighty psychiatry program directors responded to the survey and felt optimistic about their ability to teach the Psychopathology, Psychotherapy, Somatic Therapies, and Practice of Psychiatry subcompetencies., Conclusions: The PRITE measured significant improvements in medical knowledge for several of the core subcompetencies. The program director's responses would suggest that the lack of statistically significant differences found for Development and Clinical Neuroscience reflects areas in need of curricular development. The disparity between PRITE performance and program director perception of the Practice of Psychiatry subcompetency may reflect difficulties in defining the scope of this subcompetency. Overall, this suggests that structured examinations help measure improvements in certain subcompetencies and may also help identify curricular needs. However, there may be potential problems with the definition of some subcompetencies., (© 2021. Academic Psychiatry.)

Antimicrobial resistance (AMR) limits the ability to prevent and treat infection, making AMR one of the foremost threats to human and animal health. Animal agriculture's large use of antibiotics in food animals is an important factor in AMR. As such, policies to reduce antibiotic use and combat AMR in animal agriculture in the United States (US) have been in place or are developed. One key to the success of these policies in the US is understanding how a major stakeholder - veterinarians treating dairy cattle - perceive the scale of antibiotic use, the threat of AMR and the utility of antibiotic use policies. We interviewed 9 dairy veterinarians in New York State and conducted an iterative thematic analysis of their responses, through which five themes were identified: 1. veterinarians' views of the frequency and reasons for antibiotic misuse, 2. their ideas on reducing antibiotic use, 3. perceptions of AMR within the dairy industry, 4. view of organic farming and how it relates to animal welfare, and 5. the impact of consumers' beliefs on the dairy industry. Participants viewed antibiotic overuse as largely due to farmers' concern for the welfare of their cattle and desire to treat ailments swiftly. Interviewees believed that it was possible to reduce antibiotic use through regulation, such as the Veterinary Feed Directive and improved herd management activities, such as better colostrum management, culture-based mastitis treatment, and improved housing conditions. They did not view the dairy industry as a significant contributor to AMR, particularly when compared to the human medical industry. Interviewees also offered their (unsolicited) opinion on organic dairy farming in the US and expressed frustration with the limited treatment options available in organic dairy farming and how this dynamic may potentially compromise animal welfare. Finally, they commented on the impact of consumers' beliefs on the dairy industry, expressing frustration with how misinformation about the dairy industry has led to consumer driven changes. As consumer beliefs have an impact on the dairy industry, this influence could be leveraged to further decrease antibiotic use. These findings can help guide future efforts in veterinarian-client communication and the development and implementation of effective policies in New York State. These results also highlight the need for more quantitative research on antibiotic use in the dairy industry, as without this data it will be difficult to ascertain the true impact of policy interventions., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The Diagnostic and Statistical Manual (DSM) does not specifically identify one's own suicide attempt as a potential source of trauma for the development of posttraumatic stress disorder (PTSD). PTSD following a near death experience in an adolescent may occur in both the adolescent and the parent. However, suicide-attempt-related PTSD (SA-PTSD) is scarce in the literature, particularly in the pediatric population. The authors review three cases of adolescent patients or their parents in an outpatient clinical practice who displayed varying severity of SA-PTSD symptoms. Information was obtained via self-report by adolescent, parent, or both. Screening for SA-PTSD symptoms was not explicitly sought; rather patients or parents volunteered such information de novo during clinical encounters which was then explored further. One adolescent had only brief PTSD-like experiences that faded with time and did not require intervention. A second adolescent reported long-term memory loss around the circumstances of their suicide attempt that may be related to medical morbidity; their parent had significant PTSD symptoms throughout treatment, and the parent was referred to their own therapy. A third adolescent was referred for cognitive-behavioral therapy (CBT) for the treatment of pervasive PTSD symptoms from a previous suicide attempt, with symptoms improving after treatment. A qualititative analysis suggests that more severe SA-PTSD symptoms are associated with 1) multiple prior suicide attempts; 2) more severe/higher morbidity suicide attempt; and 2) previous diagnosis of PTSD in patient or parent. Assessment for SA-PTSD is important to ensure that affected patients and their families are referred for appropriate resources and treatment. Of the very small sample of three cases, two required specific referral to treat PTSD symptoms in either the adolescent or the parent. The literature about SA-PTSD is extremely scarce. Only two studies systematically examined PTSD following suicide attempt, and none of these studies were in pediatric patients, making more robust quantitative or qualitative analysis limited at this time. Therefore, more research regarding epidemiology, risk factors, and treatment is needed., Competing Interests: Conflict of interestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021.)

The effect of reflection is studied experimentally and theoretically on a high-power 110 GHz gyrotron operating in the TE 22,6 mode in 3 μ s pulses at 96 kV, 40 A. The experimental setup allows variation of the reflected power from 0 to 33 % over a range of gyrotron operating conditions. The phase of the reflection is varied by translating the reflector along the axis. Operating at a higher efficiency point, at 4:40 T with 940 kW of output power, reflected power exceeding 11% causes a switch from operation in the TE 22,6 to simultaneous operation in the TE 22,6 and TE 21,6 modes with a large decrease of the total gyrotron output power. This switching effect is in good agreement with simulations using the MAGY code. Operating at a more stable point, 4:44 T with 580 kW of output power, when the reflection is increased, the output power remains in the TE 22,6 mode but it decreases monotonically with increasing reflection, dropping to 200 kW at 33% reflection. Furthermore, at a reflection above 22%, a power modulation at 25 to 30 MHz is observed, independent of the phase of the reflected wave. Such a modulated signal may be useful in spectroscopic and other applications.

The United States regulates the use of antibiotics in agricultural settings to address the global antibiotic resistance problem. Conventional dairy cows treated with antibiotics are kept in the herd and after the withholding period milk is harvested. On organic farms, the US organic standard on antibiotic use requires sick dairy cows to be treated, but treated cows must be removed from the herd and their milk can never again be sold as certified organic. This study investigated the US public's perceptions of the organic dairy farming, antibiotic use on dairy farms, and whether these perceptions affect consumer's self-reported purchasing behavior for organic. We used a nationally representative phone-based survey of 1000 US adults and characterized participants' self-reported (i) knowledge of the legality of antibiotic use on dairy farms (conventional and organic) and (ii) frequency of purchasing organic instead of conventional dairy products, as well as several demographic and other variables. The results indicated that participants' knowledge about antibiotic use practices in dairy farming have no effect on their self-reported purchasing behavior for organic or conventional dairy products. However, respondents who were familiar with the regulations of antibiotic use on dairy farms were more likely to oppose the US organic standard on antibiotic use in dairy farming and thought that past antibiotic use should not permanently remove a cow's organic status. These findings contribute to understanding of public perceptions that shape the US dairy organic market. PRACTICAL APPLICATION: Income, employment, health and political values, but not consumers' knowledge about antibiotic use in dairy farming, affect self-reported purchasing behavior for organic dairy products. However, consumers who are familiar with the regulations of antibiotic use on US dairy farms disagree with the US organic standard on antibiotic use mandating loss of organic status for any cattle treated with antibiotics. These findings may be useful to organic markets., (© 2021 The Authors. Journal of Food Science published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Veterinarians are the main source of information for farmers regarding the responsible use of antibiotics in farm animals and how to reduce the risk of antibiotic resistance. Consequently, understanding how veterinarians perceive their clients' and colleagues' antibiotic use and their own beliefs about the development of antibiotic resistance is essential to determining areas in which antibiotic use practices can be improved to minimize the emergence of antibiotic resistance. An international cross-sectional study was carried out using a questionnaire designed to elucidate perceptions, attitudes, and concerns of dairy veterinarians regarding antibiotic use and the emergence of antibiotic resistance in dairy farming. The questionnaire was initially administered to veterinarians attending the International Bovine Mastitis Conference in Milano, Italy, 2018, followed by veterinarian members of the National Mastitis Council, and all conference registrants. A total of 71 participants from 21 countries participated in the survey, the majority were from the United States and member countries of the European Union. Logistic regression analysis was conducted to identify predictors of veterinarians' level of concern about the development of antibiotic resistance on their clients' farms. Associations were described with odds ratios (ORs) and the associated 95 % confidence intervals (95 % CIs). Free text responses where participants shared their views on the reason for overprescribing antibiotics by veterinarians were analyzed using thematic analysis. Participants perceived that nearly half of their clients overuse or inappropriately use antibiotics, and nearly half of their colleagues overprescribe or inappropriately prescribe antibiotics. After controlling for other factors, the odds of veterinarians being concerned about antibiotic resistance on dairy farms they served decreased by a factor of 0.91 for each additional year of participants' experience working with dairy cattle (OR = 0.91, 95 % CI = 0.84-0.99). Participants concerned about antibiotic resistance on clients' dairy farms were also more likely to consider better adherence to drug labelling as important for reducing farmers' antibiotic use (OR = 6.86, 95 % CI = 1.21-38.93). Thematic analysis revealed four themes surrounding the perceived reasons for veterinarians' overprescribing of antibiotics: (i) knowledge, (ii) attitudes, (iii) barriers, and (iv) rules and regulations. The study findings will aid in the development of strategies to improve antibiotic use in dairy farming and educational initiatives looking to enhance the communication between veterinarians and farmers about judicious use of antibiotics., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

The phase stability of a 140GHz, 1kW pulsed gyro-amplifier system and the phase dependence on the cathode voltage were experimentally measured. To optimize the measurement precision, the amplifier was operated at 47 kV and 1 A, where the output power was ∼ 30W. The phase was determined to be stable both pulse-to-pulse and during each pulse, so far as the cathode voltage and electron beam current are constant. The phase variation with voltage was measured and found to be 130±30°/kV, in excellent agreement with simulations. The electron gun used in this device is non-adiabatic, resulting in a steep slope of the beam pitch factor with respect to cathode voltage. This was discovered to be the dominant factor in the phase dependence on voltage. The use of an adiabatic electron gun is predicted to yield a significantly smaller phase sensitivity to voltage, and thus a more phase-stable performance. To our knowledge, these are the first phase measurements reported for a gyro-amplifier operating at a frequency above W-band., Competing Interests: Conflict of Interest The authors declare that they have no conflict of interest.

This study conceptually and empirically distinguishes two mental processes in narrative processing of food safety health messages-identification with and egocentric projection onto story characters. Two studies examined the effects of narrative autobiographical accounts of contracting foodborne illness (salmonella) because of careless food preparation. Both studies consistently found that identification increased, but egocentric projection decreased audience members' behavioral intention to perform safe food handling practices, indicating that egocentric projection and identification represent unique mental processes and yield distinct persuasive outcomes. In addition, confirmatory factor analyses provided evidence that egocentric projection and identification are distinct constructs. Implications for the role of identification and egocentric projection for understanding narrative processing and for health persuasion are discussed.

Background: Allergen immunotherapy can provide long-term benefits, including symptomatic relief and reduced disease progression, but it requires a lengthy regimen that presents barriers to patient adherence. Thus, there is a need for improved approaches to immunotherapy. Recently, several clinical trials have reported successful results from intralymphatic immunotherapy., Objective: To evaluate the efficacy, safety, and tolerability of intralymphatic immunotherapy for allergies caused by mountain cedar pollen in a proof-of-concept study., Methods: A total of 21 patients with allergic rhinoconjunctivitis because of mountain cedar pollen were randomized to receive 3 monthly intralymphatic injections of allergenic extract or placebo before the 2018-2019 mountain cedar pollen season. Safety was monitored during treatment to the end of the pollen season using structured and spontaneous reports. Clinical efficacy information was collected using a daily electronic diary of symptoms and allergy medication. Allergen-specific serum immunoglobulin E was assessed before treatment and at the end of the study., Results: There were no serious adverse events or systemic reactions in either group. A total of 4 patients experienced mild injection-site reactions. Patients receiving intralymphatic immunotherapy experienced a significant improvement in allergy symptoms and medication use relative to patients receiving placebo (P < .001), and the active treatment group had lower average total combined scores on 20 of 27 days during the peak pollen season (P < .05). There was no significant difference among groups in changes to mean mountain cedar-specific serum immunoglobulin E levels., Conclusion: In this proof-of-concept trial, intralymphatic immunotherapy was well tolerated and improved the symptoms and medication use associated with allergic rhinoconjunctivitis caused by mountain cedar pollen., Trial Registration: This study was registered at ClinicalTrials.gov under the registration number NCT03682965 before the enrollment of the first subject., (Copyright © 2020 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

We report the design and experimental demonstration of a frequency tunable terahertz gyrotron at 527 GHz built for an 800 MHz Dynamic Nuclear Polarization enhanced Nuclear Magnetic Resonance (DNP-NMR) spectrometer. The gyrotron is designed at the second harmonic ( ω = 2 ω c = 110 mA in a TE b = 110 mA in a TE 11,2,1 mode, corresponding to an efficiency of ~0.5%. The gyrotron is tunable within ~ 0.4 GHz by combining voltage and magnetic field tuning. The gyrotron has an internal mode converter that produces a Gaussian-like beam that couples to the HE 11 mode of an internal 12 mm i.d. corrugated waveguide periscope assembly leading up to the output window. An external corrugated waveguide transmission line system is built including a corrugated taper from 12 mm to 16 mm i.d. waveguide followed by 3 m of the 16 mm i.d. waveguide The microwave beam profile is measured using a pyroelectric camera showing ~ 84% HE 11 mode content.

This Letter reports the successful experimental demonstration of amplification of subterahertz radiation in a klystron with photonic crystal cavities. The klystron has six cavities, with each cavity having a series of oversized photonic crystal cells made up of a 5×3 array of square posts. The center post is removed from each cell to form a highly oversized (0.8  mm∼λ/4) beam tunnel, with power coupling from cell to cell through the tunnel. The pulsed electron beam is operated at 23.5 kV, 330 mA in a 0.5 T solenoidal field. At 93.7 GHz, a small-signal gain of 26 dB and a saturated output power of 30 W are obtained. Experimental results are in very good agreement with the predictions of a particle-in-cell code. The successful achievement of high gain operation of a photonic crystal klystron amplifier is promising for the future extension of klystron operation well into the terahertz frequency region.

We report experimental measurements of the threshold for multipactor discharges on dielectric surfaces at 110 GHz. Multipactor was studied in two geometries: electric field polarized parallel to or perpendicular to the sample surface. Measured multipactor thresholds ranged from 15 to 34  MV/m, more than 10 times higher than those found at conventional microwave frequencies. Measured thresholds were compared with prior data at lower frequencies, showing agreement with theoretical predictions that thresholds increase linearly with frequency. Measurements of the rf power dissipated in the multipactor show low dissipation (≤1%) for the parallel electric field case, but very strong dissipation for the perpendicular case, also in agreement with theoretical predictions. The agreement between experiment and theory over a wide range of frequencies provides a strong basis for the understanding of dielectric multipactor discharges.

A laser-driven semiconductor switch (LDSS) employing silicon (Si) and gallium arsenide (GaAs) wafers has been used to produce nanosecond-scale pulses from a 3 μ s, 110 GHz gyrotron at the megawatt power level. Photoconductivity was induced in the wafers using a 532 nm laser, which produced 6 ns, 230 mJ pulses. Irradiation of a single Si wafer by the laser produced 110 GHz RF pulses with a 9 ns width and >70% reflectance. Under the same conditions, a single GaAs wafer yielded 24 ns 110 GHz RF pulses with >78% reflectance. For both semiconductor materials, a higher value of reflectance was observed with increasing 110 GHz beam intensity. Using two active wafers, pulses of variable length down to 3 ns duration were created. The switch was tested at incident 110 GHz RF power levels up to 600 kW. A 1-D model is presented that agrees well with the experimentally observed temporal pulse shapes obtained with a single Si wafer. The LDSS has many potential uses in high power millimeter-wave research, including testing of high-gradient accelerator structures., (Copyright © 2019 Author(s).)

We present the first demonstration of high-power, reversed-Cherenkov wakefield radiation by electron bunches passing through a metamaterial structure. The structure supports a fundamental transverse magnetic mode with a negative group velocity leading to reversed-Cherenkov radiation, which was clearly verified in the experiments. Single 45 nC electron bunches of 65 MeV traversing the structure generated up to 25 MW in 2 ns pulses at 11.4 GHz, in excellent agreement with theory. Two bunches of 85 nC with appropriate temporal spacing generated up to 80 MW by coherent wakefield superposition, the highest rf power that metamaterial structures ever experienced without damage. These results demonstrate the unique features of metamaterial structures that are very attractive for future high-gradient wakefield accelerators, including two-beam and collinear accelerators. Advantages include the high shunt impedance for high-power generation and high-gradient acceleration, the simple and rugged structure, and a large parameter space for optimization.

Purpose: Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non-small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC., Materials and Methods: In this open-label phase II trial, patients with resected stage IA to IIIA (7 th edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy. The study was designed for 100 patients and powered to demonstrate a primary end point of 2-year disease-free survival (DFS) greater than 85%, improving on historic data of 76%., Results: Patients (N = 100) were enrolled at seven sites from January 2008 to May 2012; 13% had stage IA disease, 32% had stage IB disease, 11% had stage IIA disease, 16% had stage IIB disease, and 28% had stage IIIA disease. Toxicities were typical of erlotinib; there were no grade 4 or 5 adverse events. Forty percent of patients required erlotinib dose reduction to 100 mg per day and 16% to 50 mg per day. The intended 2-year course was achieved in 69% of patients. The median follow-up was 5.2 years, and 2-year DFS was 88% (96% stage I, 78% stage II, 91% stage III). Median DFS and overall survival have not been reached; 5-year DFS was 56% (95% CI, 45% to 66%), 5-year overall survival was 86% (95% CI, 77% to 92%). Disease recurred in 40 patients, with only four recurrences during erlotinib treatment. The median time to recurrence was 25 months after stopping erlotinib. Of patients with recurrence who underwent rebiopsy (n = 24; 60%), only one had T790M mutation detected. The majority of patients with recurrence were retreated with erlotinib (n = 26; 65%) for a median duration of 13 months., Conclusion: Patients with EGFR-mutant NSCLC treated with adjuvant erlotinib had an improved 2-year DFS compared with historic genotype-matched controls. Recurrences were rare for patients receiving adjuvant erlotinib, and patients rechallenged with erlotinib after recurrence experienced durable benefit.

We report the amplification of 250 GHz pulses as short as 260 ps without observation of pulse broadening using a photonic-band-gap circuit gyrotron traveling-wave-amplifier. The gyrotron amplifier operates with a device gain of 38 dB and an instantaneous bandwidth of 8 GHz. The operational bandwidth of the amplifier can be tuned over 16 GHz by adjusting the operating voltage of the electron beam and the magnetic field. The amplifier uses a 30 cm long photonic-band-gap interaction circuit to confine the desired TE 03 -like operating mode while suppressing lower order modes which can result in undesired oscillations. The circuit gain is >55 dB for a beam voltage of 23 kV and a current of 700 mA. These results demonstrate the wide bandwidths and a high gain achievable with gyrotron amplifiers. The amplification of picosecond pulses of variable lengths, 260-800 ps, shows good agreement with the theory using the coupled dispersion relation and the gain-spectrum of the amplifier as measured with quasi-CW input pulses.

The design and experimental results of a 140 GHz gyro-amplifier that uses a dielectric-loaded, sever-less confocal waveguide are presented. The gyro-traveling wave amplifier uses the HE 06 mode of a confocal geometry with power coupled in and out of the structure with Vlasov-type, quasi-optical couplers. Dielectric loading attached to the side of the confocal structure suppresses unwanted modes allowing zero-drive stable operation at 48 kV and 3A of beam current. The confocal gyro-amplifier demonstrated a peak circuit gain of 35 dB, a bandwidth of 1.2 GHz and a peak output power of 550 W at 140.0 GHz.

This study explores the effects of habitual health risk behaviors and self-activation on resistance to narrative persuasion. In two experiments, heavier drinkers were more resistant to an anti-binge-drinking narrative public service announcement (PSA) in which a binge drinker suffers a negative outcome. Specifically, heavier drinkers were more likely to generate counterarguments, unrealism judgments, and negative evaluations about the message compared to lighter drinkers or nondrinkers. However, activating self-concept when processing the persuasive narrative reduced unrealism judgments and negative evaluations, particularly among heavier drinkers. Self-activation also decreased perceived freedom threat among both heavier and lighter drinkers, which further led to higher perceived risk of binge drinking. Theoretical and practical implications are discussed.

The linear and nonlinear theory of a gyroamplifier using a confocal waveguide is presented. A quasi-optical approach to describing the modes of a confocal waveguide is derived. Both the equations of motion and the mode excitation equation are derived in detail. The confocal waveguide circuit has the advantage of reducing mode competition but the lack of azimuthal symmetry presents challenges in calculating the gain. In the linear regime, the gain calculated using the exact form factor for the confocal waveguide agrees with an azimuthally averaged form factor. A beamlet code including velocity spread effects has been written to calculate the linear and nonlinear (saturated) gain. It has been successfully benchmarked against the MAGY code for azimuthally symmetric cases. For the confocal waveguide, the beamlet code shows that the saturated gain is reduced when compared with results obtained using an azimuthally averaged form factor. The beamlet code derived here extends the capabilities of nonlinear gyroamplifier theory to configurations that lack azimuthal symmetry.

Once considered pathological, transgenderism is now accepted as a variant of normal sexuality. As society has become more accepting of transgenderism, increasing numbers of transgender patients have begun to seek psychiatric care, and younger populations are embracing their gender differences. There is a paucity of literature on how best to serve transgender youth in psychiatric inpatient units. In this article, we share our experience and discuss the need for practical guidelines to help the inpatient psychiatrist navigate key topics related to this population. We then present a case report to illustrate several of these issues. A major goal of this report is to increase the literature base.