Balancing dairy cattle diets for rumen nitrogen and methionine or all essential amino acids relative to metabolizable energy.

Improving the ability of diet formulation models to more accurately predict AA supply while appropriately describing requirements for lactating dairy cattle provides an opportunity to improve animal productivity, reduce feed costs, and reduce N intake. The goal of this study was to evaluate the sensitivity of a new version of the Cornell Net Carbohydrate and Protein System (CNCPS) to formulate diets for rumen N, Met, and all essential AA (EAA). Sixty-four high-producing dairy cattle were randomly assigned to 1 of the 4 following diets in a 14-wk longitudinal study: (1) limited metabolizable protein (MP), Met, and rumen N (Base), (2) adequate Met but limited MP and rumen N (Base + M), (3) adequate Met and rumen N, but limited MP (Base + MU), and (4) adequate MP, rumen N, and balanced for all EAA (Positive). All diets were balanced to exceed requirements for ME relative to maintenance and production, assuming a nonpregnant, 650-kg animal producing 40 kg of milk at 3.05% true protein and 4.0% fat. Dietary MP was 97.2, 97.5, 102.3, and 114.1 g/kg of dry matter intake for the Base, Base + M, Base + MU, and Positive diets, respectively. Differences were observed for dry matter intake and milk yield (24.1 to 24.7 and 39.4 to 41.1 kg/d, among treatments). Energy corrected milk, fat, and true protein yield were greater (2.9, 0.13, and 0.08 kg/d, respectively) in cows fed the Positive compared with the Base diet. Using the updated CNCPS, cattle fed the Base, Base + M, and Base + MU diets were predicted to have a negative MP balance (-231, -310, and -142 g/d, respectively), whereas cattle fed the Positive diet consumed 33 g of MP/d excess to ME supply. Bacterial growth was predicted to be depressed by 16 and 17% relative to adequate N supply for the Base and Base + M diets, respectively, which corresponded with the measured lower apparent total-tract NDF degradation. The study demonstrates that improvements in lactation performances can be achieved when rumen N and Met are properly supplied and further improved when EAA supply are balanced relative to requirements. Formulation using the revised CNCPS provided predictions for these diets, which were sensitive to changes in rumen N, Met, all EAA, and by extension MP supply.

[Medication reconciliation and hospital-community transition securisation: Survey of community pharmacists]. / Conciliation médicamenteuse et sécurisation de la transition hôpital­ville : enquête auprès des pharmaciens d'officine.

OBJECTIVE: To collect the community pharmacists' perception on their role in the medication reconciliation's process. METHODS: We did an observational transverse study thanks to a survey of community pharmacists working in France, conducted in 2020. A digital questionnaire was submitted to Parisian community pharmacists before being shared on two Facebook groups. The responses were analysed with Microsoft Excel® software. We calculated percentages, used Chi2 or Fisher's exact tests and did qualitative analyses. RESULTS: We collected the perception of 135 community pharmacists, the majority was women (80%), relatively young (69.6% of 40 years old or less). They were 63.7% to claim knowing the medication reconciliation, but they could not define it properly. The subject's knowledge was statistically related to age (P-value<0.001) and previous contacts of the health care facilities (P-value<0.001). The majority of interviewed pharmacist considered the transmission of information to those health facilities as relevant and feasible and they expressed their willingness to get involved. However, they were limited by some obstacles such as the non-exhaustiveness of the medicinal record, the unsecured mail and the lack of feedbacks. CONCLUSIONS: Although the community pharmacists expressed interest for the medication reconciliation process and willingness to get involved, their role remained limited. Therefore, this process needs an improvement of its organisation and a generalisation of its practice to really benefit the hospital-community transition's safety.

Reciprocal Learning Between Military and Civilian Surgeons: Past and Future Paths for Medical Innovation.

Numerous surgical advances have resulted from exchanges between military and civilian surgeons. As part of the U.S. National Library of Medicine Michael E. DeBakey Fellowship in the History of Medicine, we conducted archival research to shed light on the lessons that civilian surgery has learned from the military system and vice-versa. Several historical case studies highlight the need for immersive programs where surgeons from the military and civilian sectors can gain exposure to the techniques, expertise, and institutional knowledge the other domain provides. Our findings demonstrate the benefits and promise of structured programs to promote reciprocal learning between military and civilian surgery.

[Elder fallers: A group at risk of readmission?] / Les patients âgés chuteurs : un groupe à risque de réhospitalisation ?

OBJECTIVES: To describe older patients hospitalized for falls, at risk of readmission and priority for interventions to reduce this risk. METHODS: We conducted an observational, monocentric, prospective study (from April to June 2019). The inclusion criteria were: patients aged 75 and over, admitted to the Emergency Department for falls, consenting to the study. For patients subsequently hospitalized, the geriatric scores were determined (risk of readmission [ISAR score], state of frailty, degree of autonomy [Katz score]), and when appropriate, medication treatments were listed and compliance of patients was assessed (Girerd score). RESULTS: In three months, 154 patients were included (median age 86 years [min 75-max 103], sex ratio 0.44), of which 73 patients were hospitalized. Among these patients, 63% presented a high risk of readmission; 45.2% are likely to become frail; 72.6% were dependent. Finally, 53 of the 73 patients (72.6%) had a treatment in primary care and presented a 71.7% non-compliance or low-compliance rate. Fifty height patients (79.5%) had at least 1 drug associated with fall [min 1-max 7]. CONCLUSIONS: Older patients presenting at hospital with a fall were numerous, often likely to become frail and dependent for the majority of them. As the readmission risk is also very high in this population, future studies aiming at reducing the risk of hospital readmission are needed.

[Microvascular changes in COVID-19]. / Mikrovaskuläre Veränderungen bei COVID-19.

BACKGROUND: Clinically, coronavirus disease 2019 (COVID-19) is associated with a wide range of symptoms, which can range from mild complaints of an upper respiratory infection to life-threatening hypoxic respiratory insufficiency and multiorgan failure. OBJECTIVE: The initially identified pulmonary damage patterns, such as diffuse alveolar damage in acute lung failure, are accompanied by new findings that draw a more complex scenario. These include microvascular involvement and a wide range of associated pathologies of multiple organ systems. A back-scaling of microstructural vascular changes is possible via targeted correlation of pathological autopsy results with radiological imaging. MATERIAL AND METHODS: Radiological and pathological correlation as well as microradiological imaging to investigate microvascular involvement in fatal COVID-19. RESULTS: The cases of two COVID-19 patients are presented. Patient 1 showed a relative hypoperfusion in lung regions that did not have typical COVID-19 infiltrates; the targeted post-mortem correlation also showed subtle signs of microvascular damage even in these lung sections. Patient 2 showed both radiologically and pathologically advanced typical COVID-19 destruction of lung structures and the case illustrates the damage patterns of the blood-air barrier. The perfusion deficit of the intestinal wall shown in computed tomography of patient 2 could not ultimately clearly be microscopically attributed to intestinal microvascular damage. CONCLUSION: In addition to microvascular thrombosis, our results indicate a functional pulmonary vasodysregulation as part of the pathophysiology during the vascular phase of COVID-19. The clinical relevance of autopsies and the integration of radiological imaging findings into histopathological injury patterns must be emphasized for a better understanding of COVID-19.

Bulk and grain boundary Li-diffusion in dense LiMn2O4 pellets by means of isotope exchange and ToF-SIMS analysis.

Lithium diffusion in LiMn2O4 pellets is studied by means of isotope exchange and Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). A 6Li-enriched film deposited by Pulsed Laser Deposition (PLD) on a dense LiMn2O4 pellet with natural abundance of lithium isotopes is used to study the tracer diffusion of lithium. The measured profiles are analyzed by numerical models describing the 6Li tracer diffusion from the film into the pellet. Experiments in the Harrison type B regime of diffusion kinetics allow for the distinction and simultaneous determination of bulk and grain boundary diffusion coefficients. Changing the experimental conditions to reach Harrison type A behavior yields effective diffusion coefficients for lithium tracer diffusion in LiMn2O4. Activation energies for bulk and grain boundary diffusion were obtained from experiments at different temperatures. Our values are critically compared to previous studies.

Transurethral resection of bladder cancer on the lateral bladder wall without obturator nerve block: extent of adductor spasms using the monopolar versus bipolar technique-a prospective randomised study.

PURPOSE: To establish whether bipolar transurethral resection of tumours (bTURB) on the lateral bladder wall is superior to monopolar transurethral resection (mTURB) of such tumours. To our knowledge, this is the first prospective randomised study, which defines complete resection depending on obturator jerk as primary endpoint. METHODS: In a prospective, randomised, single centre study, 52 patients with newly diagnosed or recurrent bladder tumour on the lateral bladder wall were enrolled and randomised to undergo mTURB or bTURB; 44 patients were eligible for analysis, of whom 21 underwent mTURB and 23 bTURB. Any differences between the two techniques related to the incidence of unwanted stimulation of the obturator nerve and subsequent adductor spasms were evaluated. All procedures were carried out under laryngeal mask anaesthesia without obturator nerve block (ONB) and without drug-induced relaxation. RESULTS: Baseline characteristics of the two study groups did not differ statistically significantly. The success rate defined as complete resection of the bladder tumour without any clinically relevant adductor spasm was 61.9% in the monopolar group and 82.6% in the bipolar group (p = 0.18). CONCLUSIONS: Complete, undisturbed resection of tumours of the lateral bladder wall is feasible with mTURB and bTURB. Adductor spasms due to obturator jerk can occur suddenly with the risk of bladder perforation. We therefore support ONB when using spinal anaesthesia and drug-induced relaxation when using general anaesthesia when performing TURB on the lateral bladder wall.

Iatrogenic risk factors associated with hospital readmission of elderly patients: A matched case-control study using a clinical data warehouse.

WHAT IS KNOWN: Hospital readmission within 30 days of patient discharge has become a standard to judge the quality of hospitalizations. It is estimated that 14% of the elderly, people over 75 years old or those over 65 with comorbidities, are at risk of readmission, of which 23% are avoidable. It may be possible to identify elderly patients at risk of readmission and implement steps to reduce avoidable readmissions. OBJECTIVE: The aim of this study was to identify iatrogenic risk factors for readmission. The secondary objective was to evaluate the rate of drug-related readmissions (DRRs) among all readmissions and compare it to the rate of readmissions for other reasons. METHODS: We conducted a retrospective, matched, case-control study to identify non-demographic risk factors for avoidable readmission, specifically DRRs. The study included patients hospitalized between 1 September 2014 and 31 October 2015 in an 800-bed university hospital. We included patients aged 75 and over. Cases consisted of patients readmitted to the emergency department within 30 days of initial discharge. Controls did not return to the emergency department within 30 days. Cases and controls were matched on sex and age because they are known as readmissions risk factors. After comparison of the mean or percentage between cases and controls for each variable, we conducted a conditional logistic regression. RESULTS: The risk factors identified were an emergency admission at the index hospitalization, returning home after discharge, a history of unplanned readmissions and prescription of nervous system drugs. Otherwise, 11.4% of the readmissions were DRRs, of which 30% were caused by an overdose of antihypertensive. The number of drugs at readmission was higher, and potentially inappropriate medications were more widely prescribed for DRRs than for readmissions for other reasons. WHAT IS NEW AND CONCLUSION: In this matched case-control retrospective study, after controlling for gender and age, we identified the typical profile of elderly patients at risk of readmission. These patients had an unplanned admission at the index hospitalization and prescribed nervous system drugs at discharge from the index admission; they have a history of unplanned readmission within 30 days and return home after discharge.

Firearm Deaths in America: Can We Learn From 462,000 Lives Lost?

OBJECTIVE: We sought to determine whether state firearm legislation correlated with firearm-related fatality rates (FFR) during a 15-year period. BACKGROUND: The politicized and controversial topic of firearm legislation has been grossly understudied when the relative impact of American firearm violence is considered. Scientific evidence regarding gun legislation effectiveness remains scant. METHODS: Demographic and intent data (1999-2013) were collected from the Centers for Disease Control and Prevention's Web-Based Injury Statistics Query and Reporting System database and compared by state firearm legislation rankings with respect to FFR. State scorecards were obtained from firearm-restrictive (Brady Campaign/Law Center against Gun Violence [BC/LC]) and less-restrictive (National Rifle Association) groups. FFR were compared between restrictive and least-restrictive states during 3 periods (1999-2003, 2004-2008, 2009-2013). RESULTS: During 1999 to 2013, 462,043 Americans were killed by firearms. Overall FFR did not change during the 3 periods (10.89 ±â€Š3.99/100,000; 10.71 ±â€Š3.93/100,000; 11.14 ±â€Š3.91/100,000; P = 0.87). Within each period, least-restrictive states had greater unintentional, pediatric, and adult suicide, White and overall FFR than restrictive states (all P < 0.05). Conversely, no correlation was seen, during any of the 3 time periods, with either homicide or Black FFR-population subsets accounting for 41.7% of firearm deaths. CONCLUSIONS: Restrictive firearm legislation is associated with decreased pediatric, unintentional, suicide, and overall FFR, but homicide and Black FFR appear unaffected. Future funding and research should be directed at both identifying the most effective aspects of firearm legislation and creating legislation that equally protects every segment of the American population.

Demonstration of an efficient, photonic-based astronomical spectrograph on an 8-m telescope.

We demonstrate for the first time an efficient, photonic-based astronomical spectrograph on the 8-m Subaru Telescope. An extreme adaptive optics system is combined with pupil apodiziation optics to efficiently inject light directly into a single-mode fiber, which feeds a compact cross-dispersed spectrograph based on array waveguide grating technology. The instrument currently offers a throughput of 5% from sky-to-detector which we outline could easily be upgraded to ∼ 13% (assuming a coupling efficiency of 50%). The isolated spectrograph throughput from the single-mode fiber to detector was 42% at 1550 nm. The coupling efficiency into the single-mode fiber was limited by the achievable Strehl ratio on a given night. A coupling efficiency of 47% has been achieved with ∼ 60% Strehl ratio on-sky to date. Improvements to the adaptive optics system will enable 90% Strehl ratio and a coupling of up to 67% eventually. This work demonstrates that the unique combination of advanced technologies enables the realization of a compact and highly efficient spectrograph, setting a precedent for future instrument design on very-large and extremely-large telescopes.

Modal noise in an integrated photonic lantern fed diffraction-limited spectrograph.

In an attempt to develop a streamlined astrophotonic instrument, we demonstrate the realization of an all-photonic device capable of both multimode to single mode conversion and spectral dispersion on an 8-m class telescope with efficient coupling. The device was a monolithic photonic spectrograph which combined an integrated photonic lantern and an efficient arrayed waveguide grating device. During on-sky testing, we discovered a previously unreported type of noise that made spectral extraction and calibration extremely difficult. The source of the noise was traced to a wavelength-dependent loss mechanism between the feed fiber's multimode near-field pattern and the modal acceptance profile of the integrated photonic lantern. Extensive modeling of the photonic components replicates the wavelength-dependent loss, and demonstrates an identical effect on the final spectral output. We outline that this could be mitigated by directly injecting into the integrated photonic lantern.

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies.

The plasma free amino acid dose-response technique: A proposed methodology for determining lysine relative bioavailability of rumen-protected lysine supplements.

Estimates of Lys bioavailability of rumen-protected Lys (RP-Lys) supplements are often obtained using in vitro or 2-step in situ techniques, with little to no data determining efficacy and bioavailability in vivo. The objective of this study was to further evaluate and refine the use of the plasma free AA dose-response technique as a method for determining Lys relative bioavailability of RP-Lys supplements. Thirteen dose-response Latin square studies using 87 lactating, ruminally cannulated multiparous Holstein cows (days in milk from 55 to 315 and milk yield from 12 to 62 kg/d at the start of the studies) were conducted to measure the relative bioavailability of RP-Lys supplements. Intestinal (1 study) and abomasal (12 studies) infusions of Lys ranged from 0 to 84 g/d, and experimental periods ranged from 4 to 21 d. Basal diets were formulated to be adequate in metabolizable Met, but varied in predicted metabolizable Lys (5.04 to 6.81% of metabolizable protein). One to 4 daily blood samples were taken from the coccygeal vessels for 1 to 3 consecutive days in each period. Plasma Lys concentration in cows assigned to the control treatment (0 g/d Lys) ranged from 1.83 to 5.21% of total plasma AA, whereas that from cows duodenally or abomasally infused with Lys ranged from 2.53 to 7.51% of total plasma AA. Results from studies involving more than 2 amounts of infused Lys confirmed linearity of response. The following variables were regressed against the plasma Lys dose-response slopes generated from the Lys infusion treatments to examine their effects on the magnitude of the slopes: plasma Lys concentration of the control diet, plasma Lys concentration at the greatest amount of infused Lys, net energy of lactation and metabolizable protein balances, metabolizable protein supply, days in milk, milk yield, milk concentrations of fat, true protein, and lactose, milk true protein yield, and dry matter intake. The variable having the greatest effect on the magnitude of the dose-response slope was the plasma Lys concentration at the greatest amount infused. The relative bioavailability of evaluated RP-Lys supplements using the plasma free AA dose-response technique ranged from 5 to 87%. It was concluded that plasma free Lys increases in a linear fashion to increasing amounts of absorbed Lys and that the dose-response technique is an appropriate technique for evaluating RP-Lys supplements.

Production and nitrogen utilization in lactating dairy cows fed ground field peas with or without ruminally protected lysine and methionine.

Previous research has shown that cows fed ≥24% of the diet dry matter (DM) as field peas decreased milk yield as well as concentration and yield of milk protein, possibly due to reduced DM intake and limited supply of Lys and Met. Twelve multiparous and 4 primiparous lactating Holstein cows were randomly assigned to 1 of 4 diets in a replicated 4 × 4 Latin square design. The diets contained (DM basis) 34.8% corn silage, 15.2% grass-legume silage, 5.9% roasted soybean, 2.4% mineral-vitamin premix, 2.0% alfalfa pellets, and either (1) 36% ground corn, 2.4% soybean meal, and 1.3% urea (UR), (2) 29.7% ground corn, 9.8% soybean meal, 0.13% ruminally protected (RP) Lys, and 0.07% RP-Met (CSBAA), (3) 25% ground field peas, 12.3% ground corn, and 2.4% soybean meal (FP), or (4) FP supplemented with 0.15% RP-Lys and 0.05% RP-Met (FPAA). Our objective was to test the effects of FP versus UR, FPAA versus CSBAA, and FPAA versus FP on milk yield and composition, N utilization, nutrient digestibility, ruminal fermentation profile, and plasma concentration of AA. Milk yield did not differ across diets. Compared with cows fed UR, those fed FP had greater DM intake, concentration and yield of milk true protein, apparent total-tract digestibility of fiber, urinary excretion of purine derivatives, and concentrations of total volatile fatty acids in the rumen and Lys in plasma, and less milk urea N and ruminal NH3-N. The concentration of milk urea N, as well as the concentration and yield of milk fat increased in cows fed FPAA versus CSBAA. Moreover, cows fed FPAA had greater ruminal concentration of total volatile fatty acids, increased proportions of acetate and isobutyrate, and decreased proportions of propionate and valerate than those fed CSBAA. The plasma concentrations of His, Leu, and Phe decreased, whereas plasma Met increased and plasma Lys tended to increase in cows fed FPAA versus CSBAA. Concentration of milk true protein, but not yield, was increased in cows fed FPAA versus FP. However, cows fed FPAA showed decreased concentrations of His and Leu in plasma compared with those fed FP. Overall, compared with the CSBAA diet, feeding FPAA did not negatively affect milk yield and milk protein synthesis. Furthermore, RP-Lys and RP-Met supplementation of the FP diet did not improve milk yield or milk protein synthesis, but decreased urinary urea N excretion.

Interactions between plant-derived oestrogenic substances and the mycoestrogen zearalenone in a bioassay with MCF-7 cells.

Human and animal diets may contain several non-steroidal oestrogenic compounds which originate either from plants (phytoestrogens) or from fungi that infect plants (mycoestrogens such as zearalenone (ZEN)). Phytoestrogens may compete with ZEN in binding to the oestrogen receptor ß and thereby may counteract the oestrogenic activity of ZEN. Using a modified version of the E-screen assay, plant-derived oestrogenic substances were tested for their proliferative or anti-proliferative effect on oestrogen-dependent MCF-7 cells. The samples were additionally tested for their ability to influence the oestrogenic activity of ZEN (1 µM). Among the individual substances tested, 8-prenylnaringenin had the strongest effect, as cell proliferation was increased by 78% at the lowest concentration (0.23 µM), and by 167% at the highest concentration (29.4 µM). Coumestrol (5.83 µM) increased cell proliferation by 39%, and genistein (370 µM) by 61%, respectively. Xanthohumol and enterolactone did not stimulate cell proliferation significantly. In the co-incubation experiments with ZEN, none of the single substances was able to decrease the oestrogenic activity of ZEN. Only for 8-prenylnaringenin (14.7 and 29.4 µM) was a trend towards an increase in the ZEN-induced cell proliferation up to 72% observed. In conclusion, with the exception of 8-prenylnaringenin, no substantial interaction between phytoestrogens and the mycotoxin ZEN could be detected using a bioassays with MCF-7 cells.

Advanced Practitioners Are Peers in Trauma Performance Improvement Peer Review.

Advanced practitioners (APs) have been successfully integrated into the clinical care of injured patients. Given the expanding role of APs in trauma care, we hypothesized that APs can perform Performance Improvement and Patient Safety (PIPS) peer review at a level comparable with trauma surgeons. For Phase 1, cases previously reviewed by a trauma surgeon were randomly selected by the PIPS coordinator and peer reviewed by an AP. The trauma surgeons' and APs' reviews were compared. For Phase 2, cases requiring concurrent review were peer reviewed by both an AP and an MD, who were blinded to each other's review. Both the APs' and trauma surgeons' reviews of the same medical record were presented at a bimonthly performance improvement (PI) meeting. In Phase 1, 46 PI cases were reviewed including 22 deaths. Trauma surgeons and APs had high concordance (96.0%) regarding appropriateness or inappropriateness of care (κ = 0.774). Among disagreements, APs were 3 times more likely than trauma surgeons to determine care to be inappropriate. Trauma surgeons and APs had similarly high concordance (95.5%) regarding preventability of mortality (κ = 0.861). In Phase 2, 38 PI cases were reviewed, including 31 deaths. Trauma surgeons and APs had high concordance (89.0%) regarding appropriateness or inappropriateness of care (κ = 0.585). Among disagreements, trauma surgeons and APs had similarly high concordance (86.2%) regarding preventability of mortality (κ = 0.266). We found that APs had high concordance with trauma surgeons regarding medical record reviews and are thus able to effectively review medical records for the purposes of PIPS.

Afatinib demonstrates remarkable activity against HER2-amplified uterine serous endometrial cancer in vitro and in vivo.

BACKGROUND: Uterine serous carcinomas (USCs) are an aggressive form of uterine cancer that may rely on HER2/neu amplification as a driver of proliferation. The objective of this paper is to assess the sensitivity of USC cell lines with and without HER2/neu gene amplification to afatinib, an irreversible ErbB tyrosine kinase inhibitor, and to test the efficacy of afatinib in the treatment of HER2-amplified USC xenografts. METHODS: Eight of fifteen primary USC cell lines (four with HER2 amplification and four without) demonstrating similar in vitro growth rates were treated with scalar concentrations of afatinib. Effects on cell growth, signalling and cell cycle distribution were determined by flow cytometry assays. Mice harbouring xenografts of HER2/neu-amplified USC were treated with afatinib by gavage to determine the effect on tumour growth and overall survival. RESULTS: Primary chemotherapy-resistant USC cell lines harbouring HER2/neu gene amplification were exquisitely sensitive to afatinib exposure (mean ± s.e.m. IC50=0.0056 ± 0.0006 µM) and significantly more sensitive than HER2/neu-non-amplified USC cell lines (mean ± s.e.m. IC50=0.563 ± 0.092 µM, P<0.0001). Afatinib exposure resulted in abrogation of cell survival, inhibition of HER2/neu autophosphorylation and S6 transcription factor phosphorylation in HER2/neu overexpressing USC and inhibited the growth of HER2-amplified tumour xenografts improving overall survival (P=0.0017). CONCLUSIONS: Afatinib may be highly effective against HER2/neu-amplified chemotherapy-resistant USC. The investigation of afatinib in patients harbouring HER2/neu-amplified USC is warranted.

Methanogenic community changes, and emissions of methane and other gases, during storage of acidified and untreated pig slurry.

AIMS: Acidification with concentrated H(2)SO(4) is a novel strategy to reduce NH(3) emissions from livestock slurry. It was recently found that also CH(4) emissions from acidified slurry are reduced. This study investigated the microbiological basis and temporal stability of these effects. METHODS AND RESULTS: Pig slurry from two farms, acidified by different techniques or untreated, was stored for 83 days in a pilot-scale facility. Methanogens were characterized before and after storage by T-RFLP and qPCR targeting mcrA. Emissions of NH(3) and CH(4) during storage were quantified. Acidified slurry pH was nearly constant at values of 5·5 and 6·5. Ammonia losses were reduced by 84 and 49%, respectively, while CH(4) emission with both acidification techniques was reduced by >90%. T-RFLP fingerprints showed little effect of acidification or storage time. A major T-RF of 105 bp could represent methanogens related to Thermoplasmata (Tp). No treatment effects on gene copy numbers were seen with universal methanogen primers, whereas effects were found with Tp-specific primers. CONCLUSION: Methane emissions were reduced >90% during storage. Thermoplasmata-related methanogens could be involved in CH(4) emissions from pig slurry. SIGNIFICANCE AND IMPACT OF THE STUDY: The effect of acidification on CH(4) emissions during storage of pig slurry was quantified for the first time. Acidification with sulphuric acid holds promise as a novel greenhouse gas mitigation strategy for confined livestock production.

Missing in action: A bibliometric analysis of military research in the medical literature since 1950.

BACKGROUND: Top-tier general and specialty scientific journals serve as a bellwether for national research priorities. We hypothesize that military-relevant publications are underrepresented in the scientific literature and that such publications decrease significantly during peacetime. METHODS: We identified high impact journals in the fields of Medicine, Surgery and Critical Care and developed Boolean searches for military-focused topics using National Library of Medicine Subject Headings terms. A PubMed search from 1950 to 2020 returned the number of research publications in relevant journals and the rate of military-focused publications by year. Rates of military publications were compared between peacetime and wartime. Publication rate trends were modeled with a quadratic function controlling for the start of active conflict and total casualty numbers. Baseline proportions of military physicians relative to the civilian sector served to estimate expected publication rates. Comparisons were performed using Pearson's χ 2 and Mann-Whitney U test, with p < 0.05 considered a significant difference. RESULTS: From 1950 to 2020, a total of 716,340 manuscripts were published in the journals queried. Of these, military-relevant manuscripts totaled 4,052 (0.57%). We found a significant difference in the rate of publication during times of peace and times of war (0.40% vs. 0.69%, p < 0.001). Subgroup analysis found significantly reduced rates of publication in medical and critical care journals during peacetime. For each conflict, the percentage of military-focused publications peaked during periods of war but then receded below baseline levels within a median of 2.5 years (interquartile range, 1.5-3.8 years) during peacetime. The proportion of military-focused publications never reached the current proportion of military physicians in the workforce. CONCLUSION: There is marked reduction in rates of publication for military-focused articles in high impact journals during peacetime. Military-focused articles are underrepresented in high-impact journals. Investigators of military-relevant topics and editors of high-impact journals should seek to close this gap.