Regulated Proteolysis of MutSγ Controls Meiotic Crossing Over.

Crossover recombination is essential for accurate chromosome segregation during meiosis. The MutSγ complex, Msh4-Msh5, facilitates crossing over by binding and stabilizing nascent recombination intermediates. We show that these activities are governed by regulated proteolysis. MutSγ is initially inactive for crossing over due to an N-terminal degron on Msh4 that renders it unstable by directly targeting proteasomal degradation. Activation of MutSγ requires the Dbf4-dependent kinase Cdc7 (DDK), which directly phosphorylates and thereby neutralizes the Msh4 degron. Genetic requirements for Msh4 phosphorylation indicate that DDK targets MutSγ only after it has bound to nascent joint molecules (JMs) in the context of synapsing chromosomes. Overexpression studies confirm that the steady-state level of Msh4, not phosphorylation per se, is the critical determinant for crossing over. At the DNA level, Msh4 phosphorylation enables the formation and crossover-biased resolution of double-Holliday Junction intermediates. Our study establishes regulated protein degradation as a fundamental mechanism underlying meiotic crossing over.

Spatial Patterning of Spontaneous and Medically Indicated Preterm Birth in Philadelphia.

Preterm birth (PTB) remains a key public health issue that disproportionately affects Black individuals. Since spontaneous PTB (sPTB) and medically indicated PTB (mPTB) may have different causes and interventions, we quantified racial disparities for sPTB and mPTB, and we characterized the geographic patterning of these phenotypes, overall and according to race/ethnicity. We examined a pregnancy cohort of 83,952 singleton births at 2 Philadelphia hospitals from 2008-2020, and classified each PTB as sPTB or mPTB. We used binomial regression to quantify the magnitude of racial disparities between non-Hispanic Black and non-Hispanic White individuals, then generated small area estimates by applying a Bayesian model that accounts for small numbers and smooths estimates of PTB risk by borrowing information from neighboring areas. Racial disparities in both sPTB and mPTB were significant (relative risk of sPTB = 1.83, 95% confidence interval: 1.70, 1.98; relative risk of mPTB = 2.20, 95% confidence interval: 2.00, 2.42). The disparity was 20% greater in mPTB than sPTB. There was substantial geographic variation in PTB, sPTB, and mPTB risks and racial disparity. Our findings underscore the importance of distinguishing PTB phenotypes within the context of public health and preventive medicine. Future work should consider social and environmental exposures that may explain geographic differences in PTB risk and disparities.

The Nitrous Oxide Project: assessment of advocacy and national directives to deliver mitigation of anaesthetic nitrous oxide.

The environmental emissions attributed to anaesthetic nitrous oxide across the NHS are comparable to the carbon dioxide released by 135,000 flights from Frankfurt to New York. Much of these emissions are attributable to cumbersome and inadequately managed piped systems, resulting in excessive loss and waste. Since 2020, multiple hospital sites have been engaging with the Nitrous Oxide Project, a quality improvement method supporting a 'lean systems' approach to the provision of nitrous oxide. This review considers the frameworks supporting medical gas management in UK healthcare systems, and the impact of professional advocacy and medical gas stewardship to drive anaesthetic nitrous oxide mitigation in the NHS. Nitrous oxide mitigation efforts by grassroots and professional advocacy networks are enhanced through national centralised emission monitoring, distribution of data, technical information and provision of quality analysis. Given the climate harms of nitrous oxide, concerted efforts should be made to rationalise its use, and resources should be committed to supporting this at local, regional and national levels.

Pharmacy technicians trained as community health workers: A prospective multicenter cohort study.

BACKGROUND: Community health workers (CHWs) are health professionals who are experts in linking patients to health resources. Although CHWs are employed in a variety of health institutions, access to their services may be challenging for patients in underserved locations. Community pharmacies are uniquely positioned to mitigate this barrier as they provide readily accessible care for patients residing in these areas. OBJECTIVES: To 1) quantify and report the CHW services provided by certified pharmacy technicians (CPhTs) in an underserved population and 2) provide an initial framework for the implementation of CHW services in community pharmacies or similar health care settings. METHODS: This prospective cohort study reports the findings of training CPhTs as CHWs in 3 independent community pharmacies from January 1, 2021 to July 1, 2021. CPhT-CHWs conducted monthly visits by phone, patient home, or pharmacy and documented services using a standardized assessment form. Descriptive statistics were used to summarize the baseline characteristics of the patient population, service codes, types of services and referrals made, and time spent per visit by CPhT-CHWs. RESULTS: A total of 198 patient visits by phone, patient home, or at the pharmacy were completed in a 6-month timespan. During these visits, the CPhT-CHW provided 351 services (203 primary services and 149 secondary services) and completed 51 referrals. The average time spent per visit (standard deviation) was 15.5 (11.5) 68.9 (35.4), and 30.6 (16.8) minutes for phone, home, and pharmacy visits, respectively. Patient home visits resulted in the highest average primary services per visit, longest time spent with the patient, and accounted for a majority of social services. CONCLUSION: CPhT-CHWs were able to use various methods to contact these patients to further develop patient-to-provider and patient-to-pharmacy relationships. Training CPhTs as CHWs can be an effective way to increase patient contact and provide additional health services.

Changes in Surgical Management of the Axilla Over 11 Years - Report on More Than 1500 Breast Cancer Patients Treated with Neoadjuvant Chemotherapy on the Prospective I-SPY2 Trial.

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.

Preventable deaths involving sepsis in England and Wales, 2013-2022: a systematic case series of coroners' reports.

PURPOSE: Coroners' Prevention of Future Death (PFDs) reports are an under-utilized resource to learn about preventable deaths in England and Wales. We aimed to identify sepsis-related PFDs and explore the causes and concerns in this subset of preventable sepsis deaths. METHODS: Four thousand three hundred five reports were acquired from the Courts and Tribunals Judiciary website between July 2013 and November 2022, which were screened for sepsis. Demographic information, coroners concerns and responses to these reports were extracted and analyzed, including a detailed paediatric subgroup analysis. RESULTS: Two hundred sixty-five reports (6% of total PFDs) involved sepsis-related deaths. The most common cause of death in these reports was "sepsis without septic shock" (42%) and the most common site of infection was the respiratory system (18%) followed by gastrointestinal (16%) and skin (13%) infections. Specific pathogens were named in few reports (27%). Many deaths involved multimorbid patients (49%) or those with recent surgery (26%). Coroners named 773 individual concerns, the most frequent were: a failure to keep accurate records or notes (28%), failure in communication or handover (27%) or failure to recognize risk factors or comorbidities (20%). Paediatric cases frequently reported issues with sepsis screening tools (26%). Sepsis PFDs resulted in 421 individual reports being sent, of which 45% received no response. Most organisations who did respond acknowledged concerns and initiated a new change (74%). CONCLUSION: Sepsis-related PFDs provide valuable insights into preventable causes of sepsis and identify important sources of improvement in sepsis care. Wider dissemination of findings is vital to learn from these reports.

Have Therapeutics Enhanced Our Knowledge of Axial Spondyloarthritis?

PURPOSE OF REVIEW: An overview of how the treatment landscape of axial spondyloarthritis (axSpA) has shaped our understanding of the disease. RECENT FINDINGS: Prior to the millennium, non-steroidal anti-inflammatory drugs (NSAIDs) were the only treatment for axSpA, yet only 30% of patients responded and many developed side effects. In 2003, the first biological disease-modifying drug (bDMARD) was licensed for axSpA which substantially improved outcomes in comparison to NSAIDs. In 2022, there are now several bDMARDs for axSpA; however, they too are not universally efficacious in treating axial inflammation and may have deleterious effects on extramusculoskeletal manifestations. Nevertheless, successful or not, each bDMARD gives invaluable insight into axSpA immunobiology. This review discusses how much we have learned from the use of bDMARDs in axSpA, how this has redefined our understanding of the disease, and how we might use this knowledge to develop new and better treatments for axSpA in the future.

Preventable deaths involving opioids in England and Wales, 2013-2022: a systematic case series of coroners' reports.

BACKGROUND: Opioid deaths have increased in England and Wales. Coroners' Prevention of Future Deaths reports (PFDs) provide important insights that may enable safer use and avert harms, yet reports implicating opioids have not been synthesized. We aimed to identify opioid-related PFDs and explore coroners' concerns to prevent future deaths. METHODS: In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022, obtained by web scraping the UK's Courts and Tribunals Judiciary website. PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners. RESULTS: Opioids were involved in 219 deaths reported in PFDs (5·6% of PFDs), equating to 4418 years of life lost (median 33 years/person). Morphine (29%), methadone (23%) and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to National Health Service (NHS) organizations (51%), but response rates were low overall (47%). CONCLUSIONS: Opioids could be used more safely if coroners' concerns in PFDs were addressed by national organizations such as NHS bodies, government agencies and policymakers, as well as individual prescribing clinicians.

Experiences of patients enrolled and staff involved in the prehabilitation of elective patients undergoing cardiac surgery trial: a nested qualitative study.

The purpose of this study was to understand the views and experiences of patients enrolled and staff involved in the prehabilitation of elective patients undergoing cardiac surgery trial. This sub-study was informed by normalisation process theory, a framework for evaluating complex interventions, and used consecutive sampling to recruit patients assigned to both the intervention and control groups. Patients and all staff involved in delivering the trial were invited to participate in focus groups, which were recorded, transcribed verbatim and subjected to reflexive thematic analysis. Five focus groups were held comprising 24 participants in total (nine patients assigned to the prehabilitation; seven assigned to control; and eight staff). Five themes were identified. First, preparedness for surgery reduced fear, where participants described that knowing what to expect from surgery and preparing the body physically increased feelings of control and subsequently reduced apprehension regarding surgery. Second, staff were concerned but trusted in a safe environment, describing how, despite staff's concerns regarding the risks of exercise in this population, the patients felt safe in their care whilst participating in an exercise programme in hospital. Third, rushing for recovery and the curious carer, where patients from both groups wanted to mobilise quickly postoperatively whilst staff visited patients on the ward to observe their recovery progress. Fourth, to survive and thrive postoperatively, reflecting staff and patients' expectations from the trial and what motivated them to participate. Fifth, benefits are diluted by lengthy waiting periods, reflecting the frustration felt by patients waiting for their surgery after completing the intervention and the fear about continuing exercise at home before they had been 'fixed'. To conclude, functional exercise capacity may not have improved following prehabilitation in people before elective cardiac surgery due to concerns regarding the safety of exercise that may have hindered delivery and receipt of the intervention. Instead, numerous non-physical benefits were elicited. The information from this qualitative study offers valuable recommendations regarding refining a prehabilitation intervention and conducting a subsequent trial.

A randomised controlled trial of prehabilitation in patients undergoing elective cardiac surgery.

The feasibility, safety and efficacy of prehabilitation in adult patients awaiting elective cardiac surgery are unknown. A total of 180 participants undergoing elective cardiac surgery were allocated randomly to receive either standard pre-operative care or prehabilitation, consisting of pre-operative exercise and inspiratory muscle training. The primary outcome was change in six-minute walk test distance from baseline to pre-operative assessment. Secondary outcomes included change in inspiratory muscle strength (maximal inspiratory pressure); sarcopenia (handgrip strength); quality of life and compliance. Safety outcomes were pre-specified surgical and pulmonary complications and adverse events. All outcomes were assessed at baseline; at pre-operative assessment; and 6 and 12 weeks following surgery. Mean (SD) age was 64.7 (10.2) years; 33/180 (18%) were women. In total, 65/91 (71.4%) participants who were allocated to prehabilitation attended at least four of eight supervised in-hospital exercise classes; participants aged > 50 years were more likely than younger participants to attend (odds ratio (95%CI) of 4.6 (1.0-25.1)). Six-minute walk test was not significantly different between groups (mean difference (95%CI) -7.8 m (-30.6-15.0), p = 0.503) in the intention-to-treat analysis. Subgroup analyses based on tests for interaction indicated improvements in six-minute walk test distance were larger amongst sarcopenic patients in the prehabilitation group (p = 0.004). Change in maximal inspiratory pressure from baseline to all time-points was significantly greater in the prehabilitation group, with the greatest mean difference (95%CI) observed 12 weeks after surgery (10.6 cmH2 O (4.6-16.6) cmH2 O, p < 0.001). There were no differences in handgrip strength or quality of life up to 12 weeks after surgery. There was no significant difference in postoperative mortality (one death in each group), surgical or pulmonary complications. Of 71 pre-operative adverse events, six (8.5%) were related to prehabilitation. The combination of exercise and inspiratory muscle training in a prehabilitation intervention before cardiac surgery was not superior to standard care in improving functional exercise capacity measured by six-minute walk test distance pre-operatively. Future trials should target patients living with sarcopenia and include inspiratory muscle strength training.

Rapid Electrophilic Cysteine Arylation with Pyridinium Salts.

Here, we present a series of fluorinated cationic reagents that enable rapid arylation of cysteine under mild conditions compatible with proteins and peptides. The highly polarized C-F bond and attractive nucleophile-electrophile Coulombic interactions substantially accelerate cysteine arylation, leading to unusually high rate constants on the order of 100 M-1·s-1 and allowing for equimolar labeling of substrates at micromolar concentrations. The synthetic modularity of this approach promotes the direct coupling of structurally diverse phenol-containing functional motifs to cysteine residues of biomacromolecules with high efficiency. This user-friendly chemistry enables fast bond formation between commonly used bioconjugation partners, thus greatly streamlining the synthetic chemistry workflow, and can be easily developed as convenient kits for chemical biology and medicinal chemistry applications.

Imaging joint infections using D-methyl-11C-methionine PET/MRI: initial experience in humans.

PURPOSE: Non-invasive imaging is a key clinical tool for detection and treatment monitoring of infections. Existing clinical imaging techniques are frequently unable to distinguish infection from tumors or sterile inflammation. This challenge is well-illustrated by prosthetic joint infections that often complicate joint replacements. D-methyl-11C-methionine (D-11C-Met) is a new bacteria-specific PET radiotracer, based on an amino acid D-enantiomer, that is rapidly incorporated into the bacterial cell wall. In this manuscript, we describe the biodistribution, radiation dosimetry, and initial human experience using D-11C-Met in patients with suspected prosthetic joint infections. METHODS: 614.5 ± 100.2 MBq of D-11C-Met was synthesized using an automated in-loop radiosynthesis method and administered to six healthy volunteers and five patients with suspected prosthetic joint infection, who were studied by PET/MRI. Time-activity curves were used to calculate residence times for each source organ. Absorbed doses to each organ and body effective doses were calculated using OLINDA/EXM 1.1 with both ICRP 60 and ICRP 103 tissue weighting factors. SUVmax and SUVpeak were calculated for volumes of interest (VOIs) in joints with suspected infection, the unaffected contralateral joint, blood pool, and soft tissue background. A two-tissue compartment model was used for kinetic modeling. RESULTS: D-11C-Met was well tolerated in all subjects. The tracer showed clearance from both urinary (rapid) and hepatobiliary (slow) pathways as well as low effective doses. Moreover, minimal background was observed in both organs with resident micro-flora and target organs, such as the spine and musculoskeletal system. Additionally, D-11C-Met showed increased focal uptake in areas of suspected infection, demonstrated by a significantly higher SUVmax and SUVpeak calculated from VOIs of joints with suspected infections compared to the contralateral joints, blood pool, and background (P < 0.01). Furthermore, higher distribution volume and binding potential were observed in suspected infections compared to the unaffected joints. CONCLUSION: D-11C-Met has a favorable radiation profile, minimal background uptake, and fast urinary extraction. Furthermore, D-11C-Met showed increased uptake in areas of suspected infection, making this a promising approach. Validation in larger clinical trials with a rigorous gold standard is still required.

Identification of Preanesthetic History Elements by a Natural Language Processing Engine.

BACKGROUND: Methods that can automate, support, and streamline the preanesthesia evaluation process may improve resource utilization and efficiency. Natural language processing (NLP) involves the extraction of relevant information from unstructured text data. We describe the utilization of a clinical NLP pipeline intended to identify elements relevant to preoperative medical history by analyzing clinical notes. We hypothesize that the NLP pipeline would identify a significant portion of pertinent history captured by a perioperative provider. METHODS: For each patient, we collected all pertinent notes from the institution's electronic medical record that were available no later than 1 day before their preoperative anesthesia clinic appointment. Pertinent notes included free-text notes consisting of history and physical, consultation, outpatient, inpatient progress, and previous preanesthetic evaluation notes. The free-text notes were processed by a Named Entity Recognition pipeline, an NLP machine learning model trained to recognize and label spans of text that corresponded to medical concepts. These medical concepts were then mapped to a list of medical conditions that were of interest for a preanesthesia evaluation. For each condition, we calculated the percentage of time across all patients in which (1) the NLP pipeline and the anesthesiologist both captured the condition; (2) the NLP pipeline captured the condition but the anesthesiologist did not; and (3) the NLP pipeline did not capture the condition but the anesthesiologist did. RESULTS: A total of 93 patients were included in the NLP pipeline input. Free-text notes were extracted from the electronic medical record of these patients for a total of 9765 notes. The NLP pipeline and anesthesiologist agreed in 81.24% of instances on the presence or absence of a specific condition. The NLP pipeline identified information that was not noted by the anesthesiologist in 16.57% of instances and did not identify a condition that was noted by the anesthesiologist's review in 2.19% of instances. CONCLUSIONS: In this proof-of-concept study, we demonstrated that utilization of NLP produced an output that identified medical conditions relevant to preanesthetic evaluation from unstructured free-text input. Automation of risk stratification tools may provide clinical decision support or recommend additional preoperative testing or evaluation. Future studies are needed to integrate these tools into clinical workflows and validate its efficacy.

Antibiotic Cycling Reverts Extensive Drug Resistance in Burkholderia multivorans.

Antibiotic collateral sensitivity, in which acquired resistance to one drug leads to decreased resistance to a different drug, occurs in Burkholderia multivorans. Here, we observed that treatment of extensively drug-resistant variants evolved from a cystic fibrosis (CF) sputum sample isolate with either meropenem or sulfamethoxazole-trimethoprim, depending on past resistance phenotypes, resulted in increased sensitivity to five different classes of antibiotics. We further identified mutations, including putative resistance-nodulation-division efflux pump regulators and uncharacterized pumps, that may be involved in this phenotype in B. multivorans.

Chest pain mimicking pulmonary embolism may be a common presentation of COVID-19 in ambulant patients without other typical features of infection.

BACKGROUND: Radiological and pathological studies in severe COVID-19 pneumonia (SARS-CoV-2) have demonstrated extensive pulmonary immunovascular thrombosis and infarction. This study investigated whether these focal changes may present with chest pain mimicking pulmonary emoblism (PE) in ambulant patients. METHODS: CTPAs from outpatients presenting with chest pain to Leeds Teaching Hospital NHS Trust 1st March to 31 May 2020 (n = 146) and 2019 (n = 85) were compared. Regions of focal ground glass opacity (GGO), consolidation and/or atelectasis (parenchymal changes) were determined, and all scans were scored using British Society for Thoracic Imaging (BSTI) criteria for COVID-19, and the 2020 cohort was offered SARS-CoV-2 antibody testing. RESULTS: Baseline demographic and clinical data were similar between groups with absence of fever, normal lymphocytes and marginally elevated CRP and D-Dimer values. Evidence of COVID-19 or parenchymal changes was observed in 32.9% (48/146) of cases in 2020 compared to 16.5% (14/85) in 2019 (P = 0.007). 11/146 (7.5%) patients met BSTI criteria for COVID-19 in 2020 compared with 0/14 in 2019 (P = 0.008). 3/39 patients tested had detectable COVID-19 antibodies (2 with parenchymal changes and 1 with normal parenchyma) however 0/6 patients whose CTPA met BSTI criteria "likely/suspicious for COVID-19" and attended antibody testing were SARS-CoV-2 antibody positive. CONCLUSIONS: 32.8% ambulatory patients with suspected PE in 2020 had parenchymal changes with 7.5% diagnosed as COVID-19 infection by imaging criteria, despite the absence of other COVID-19 symptoms. These findings suggest that localized COVID-19 pneumonitis with immunothrombosis occurs distal to the bronchiolar arteriolar circulation, causing pleural irritation and chest pain without viraemia, accounting for the lack of fever and systemic symptoms.

Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Mapping of a novel major effect Hessian fly field partial-resistance locus in southern soft red winter wheat line LA03136E71.

KEY MESSAGE: Hessian fly resistance has centralized around resistance loci that are biotype specific. We show that field resistance is evident and controlled by a single locus on chromosome 7D. Hessian flies (Mayetiola destructor Say) infest and feed upon wheat (Triticum aestivum L) resulting in significant yield loss. Genetically resistant cultivars are the most effective method of Hessian fly management. Wheat breeders in the southern USA have observed cultivars exhibiting a "field resistance" to Hessian fly that is not detectable by greenhouse assay. The resistant breeding line "LA03136E71" and susceptible cultivar "Shirley" were crossed to develop a population of 200 random F4:5 lines using single seed descent. The population was evaluated in a total of five locations in North Carolina during the 2019, 2020, and 2021 seasons. A subsample of each plot was evaluated for the total number of tillers, number of infested tillers, and total number of larvae/pupae. From these data, the percent infested tillers, number of larvae/pupae per tiller, and the number of larvae/pupae per infested tiller were estimated. In all within and across environment combinations for all traits recorded, the genotype effect was significant (p < 0.05). Interval mapping identified a single large effect QTL distally on the short arm of chromosome 7D for all environment-trait combinations. This locus was identified on a chromosome where no other Hessian fly resistance/tolerance QTL has been previously identified. This novel Hessian fly partial-resistance QTL is termed QHft.nc-7D. Fine mapping must be conducted in this region to narrow down the causal agents responsible for this trait, and investigation into the mode of action is highly suggested.

Editorial Commentary: Fluoroscopy Is Seldom Required During Knee Posterolateral Reconstruction.

Identifying the structures of the lateral knee is critical during knee posterolateral corner reconstruction. Several methods exist that can help estimate the femoral insertions of these structures on lateral radiographs. However, it is important to recognize the limitations of these methods and that anatomic visualization is often more practical and more accurate. Until percutaneous or more minimally invasive techniques become standardized, intraoperative fluoroscopy is seldom needed or used for posterolateral corner reconstruction, whereas radiographic analysis of lateral knee structures could be of benefit in cases of failed reconstruction to assess tunnel placement.

The quality of e-fit notes issued in secondary care.

BACKGROUND: Few data are available on the pattern of use of fit notes issued in secondary care settings. AIMS: To evaluate the pattern and quality of e-fit notes issued in an NHS Trust. METHODS: Anonymized data on patients admitted to Guy's and St Thomas' NHS Foundation Trust (London, UK) who had an e-fit note issued from 1 January to 31 August 2017 were analysed using descriptive statistical methods. Thematic analysis was used to group the free-text comments into distinct categories and themes. RESULTS: A total of 815 fit notes were issued during the study period. A total of 659 (81%) fit notes advised that patients were 'not fit' for work, whilst 156 (19%) advised that they 'may be fit' for work. The specialty with the highest proportion of patients assessed as may be fit was plastic surgery 46/104 (44%), whilst the lowest was ear, nose and throat surgery 0/57 (0%). The majority 151/156 (97%) of fit notes which advised that patients may be fit for work used the tick-box sections on the fit note to recommend work modifications. Of the free-text comments in section 4 of the 'may be fit' e-fit notes issued, 91/114 (80%) were related to the functional ability of patients. CONCLUSIONS: Our study suggests that doctors in secondary care are more willing to use the 'may be fit' option on the fit note than primary care practitioners. Most fit notes, which advised that a patient may be fit for work, suggested workplace modifications.

A Modified Pontic Appliance for Missing Maxillary Incisors.

A modified pontic technique is presented that simplifies the management of patients with missing anterior teeth during the course of comprehensive orthodontic care. This technique demonstrates a lingual arch attached to lingual sheaths with the pontic placed on the lingual arch. Information presented includes appliance design, improved bond strength of the bracket on the pontic tooth, preparing the appliance for use as anchorage, and the incorporation of an anterior biteplate in the appliance. A modified pontic appliance improves esthetics and function when treating patients with missing maxillary anterior teeth.