Generic approach to assess the measuring performance of total-radiated power quantities by multi-channel resistive bolometer diagnostics on fusion experiments.

On present-day magnetic-confinement fusion experiments, the performance of multi-channel bolometer diagnostics has typically evolved over time through experience with earlier versions of the diagnostic and experimental results obtained. For future large-scale fusion experiments and reactors, it is necessary to be able to predict the performance as a function of design decisions and constraints. A methodology has been developed to predict the accuracy with which the volume-integrated total radiated power can be estimated from the measurements by a resistive bolometer diagnostic, considering, in particular, its line-of-sight geometry, étendues of individual lines of sight, bolometer-sensor characteristics, and the expected noise level that can be obtained with its electronics and signal chain. The methodology depends on a number of assumptions in order to arrive at analytical expressions but does not restrict the final implementation of data-processing of the diagnostic measurements. The methodology allows us to predict the performance in terms of accuracy, total-radiated power level, and frequency or time resolution and to optimize bolometer-sensor characteristics for a set of performance requirements. This is illustrated for the bolometer diagnostic that is being designed for the ITER experiment. The reasonableness, consequences, and limitations of the assumptions are discussed in detail.

Efficient management of new patient referrals to a breast service: the safe introduction of an advanced nurse practitioner-led telephone breast pain service.

INTRODUCTION: There has been an almost 100% increase in referrals to breast cancer diagnostic clinics in the past decade. Breaching of the two-week cancer referral target is now commonplace, potentially delaying diagnoses of breast malignancy in many women. Almost one in five of these referrals are women with mastalgia, not a symptom linked to breast cancer. The objective of the study was the safe introduction of an advanced nurse practitioner-led telephone service for women with mastalgia to improve the service for women and create capacity for those with "red flag" breast symptoms. METHODS: Referrals to clinic were triaged, women with mastalgia only were directed to a telephone-based assessment clinic and symptoms evaluated using a multidisciplinary created proforma. RESULTS: Within 23 months, 1,427 women were assessed in the breast pain telephone assessment clinic: 863 (61%) were aged over 40 and 564 (39%) aged under 40. A total of 1,238 underwent telephone assessment. Reassurance and discharge only was needed for 365 (26%). The aetiology of pain was identified as musculoskeletal in 1,104/1,238 (89%) of patients, with only 39/1,238 (3.2%) identified as having true breast pain. Additional symptoms were mentioned by 264 women (18%) during the consultation; all immediately redirected back to a diagnostic clinic. Mammography was undertaken in 609 women (43%). Seven women (0.6%) were diagnosed with a breast malignancy. Patient survey indicated that 93% of patients were satisfied with the care received and 97% said they would recommend the service to a family member or friend. CONCLUSIONS: Although face-to-face assessments for breast pain remain the standard practice in many breast units, data indicating the safety of a telephone assessment clinic, along with high levels of patient satisfaction, question whether services can be delivered differently.

A contemporary analysis of the pre- and intraoperative recognition of multigland parathyroid disease.

BACKGROUND: Despite advances in biochemical and radiological identification of parathyroid gland enlargement, primary hyperparathyroidism (PHPT) due to sporadic multigland parathyroid disease (MGPD) remains a perioperative diagnostic dilemma. Failure to recognise MGPD pre- or intraoperatively may negatively impact surgical cure rates and result in persistent PHPT and ongoing patient morbidity. METHODS: We have conducted a comprehensive review of published literature in attempt to determine factors that could aid in reliably diagnosing sporadic MGPD pre- or intraoperatively. We discuss preoperative clinical features and examine pre- and intraoperative biochemical and imaging findings concentrating on those areas that give practicing surgeons and the wider multi-disciplinary endocrine team indications that a patient has MGDP. This could alter surgical strategy. CONCLUSION: Biochemistry can provide diagnosis of PHPT but cannot reliably discriminate parathyroid pathology. Histopathology can aid diagnosis between MGPD and adenoma, but histological appearance can overlap. Multiple negative imaging modalities indicate that MGPD may be more likely than a single parathyroid adenoma, but the gold standard for diagnosis is still intraoperative identification during BNE. MGPD remains a difficult disease to both diagnose and treat.

Assessment of prescribing pattern of drugs and completeness of prescriptions as per the World Health Organization prescribing indicators in various Indian tertiary care centers: A multicentric study by Rational Use of Medicines Centers-Indian Council of Medical Research network under National Virtual Centre Clinical Pharmacology activity.

OBJECTIVE: The rational use of medicines as per the World Health Organization (WHO) should be practiced globally. However, data regarding the completeness of the prescriptions and their rational use is lacking from developing countries like India. Thus, the aim of this study was to assess the prescribing patterns of drugs and completeness of prescriptions as per WHO core drug use and complementary indicators to provide real-life examples for the Indian Council of Medical Research (ICMR) online prescribing skill course for medical graduates. METHODS: Prescriptions of the patients, fulfilling inclusion criteria, attending Outpatient Departments of various specialties of tertiary care hospitals, were collected by thirteen ICMR Rational use of medicines centers located in tertiary care hospitals, throughout India. Prescriptions were evaluated for rational use of medicines according to the WHO guidelines and for appropriateness as per standard treatment guidelines using a common protocol approved by local Ethics committees. RESULTS: Among 4838 prescriptions, an average of about three drugs (3.34) was prescribed to the patients per prescription. Polypharmacy was noted in 83.05% of prescriptions. Generic drugs were prescribed in 47.58% of the prescriptions. Further, antimicrobials were prescribed in 17.63% of the prescriptions and only 4.98% of prescriptions were with injectables. During the prescription evaluation, 38.65% of the prescriptions were incomplete due to multiple omissions such as dose, duration, and formulation. CONCLUSION: Most of the parameters in the present study were out of the range of WHO-recommended prescribing indicators. Therefore, effective intervention program, like training, for the promotion of rational drug use practice was recommended to improve the prescribing pattern of drugs and the quality of prescriptions all over the country.

Point-of-care ultrasound educational interventions in the neonatal intensive care unit: A systematic review.

OBJECTIVE: The benefits of point-of-care ultrasound (POCUS) in the neonatal intensive care unit (NICU) have been widely recognized, but education on this area of practice remains variable. We reviewed published educational interventions regarding POCUS use in the NICU and whether they have led to sustainable increases in POCUS use. METHODS: A systematic search of 6 databases was performed for publications from January 2000 to March 2021. Studies with quantitative data related to POCUS educational interventions in the NICU were included. Data on number of participants and roles, educational intervention, curriculum description, and project outcome measures (including sustainability) was extracted. RESULTS: The search resulted in 686 articles, of which nine studies met the inclusion criteria. Educational interventions included didactic sessions, simulation practice, animal practice, and practice in real patients. The most common assessment was based on the quality and accuracy of the images. At the participant level, the average time to reach proficiency ranged from eight hours and thirty-six minutes to five months, and none of the studies evaluated sustainability of POCUS use after the intervention. CONCLUSION: There is a lack of standardized training modules and assessments for POCUS use in the NICU. Given that none of the studies addressed sustainability or standardized training, we recommend that a standardized training protocol and assessment tool is developed and studied longitudinally; and that barriers to sustainable POCUS use in the NICU (such as billing issues and a lack of POCUS machines and instructors) be systematically addressed as part of this work.

Patient reported outcome measures in a cohort of patients at high risk of breast cancer treated by bilateral risk reducing mastectomy and breast reconstruction.

BACKGROUND: Many women with increased lifetime risk of developing breast cancer, due to pathogenic gene variants or family history, choose to undergo bilateral risk reducing mastectomies (BRRM). Patient reported outcome measures (PROMS) are an increasingly important part of informed consent but are little studied in women undergoing BRRM. METHODS: We used a validated PROMS tool for breast reconstruction (BREAST-Q) in 297 women who had BRRM and breast reconstruction, 81% of whom had no malignancy (Benign Group, BG) and 19% in whom a perioperative breast cancer was diagnosed (Cancer Group, CG). 128 women also completed a Hospital Anxiety & Depression Score (HADS) questionnaire to test if preoperative HADS score could predict PROMS outcomes. RESULTS: Women in the CG had lower PROMS scores for satisfaction with their breasts, nipple reconstruction and sexual wellbeing. Both groups reported equal satisfaction with BRRM outcome and psychosocial well-being. Physical well-being PROMS of the abdomen and chest were high in women in both groups as were scores for satisfaction with the care they received. The CG group reported suboptimal quality of patient information. A higher presurgical HADS anxiety score predicted less favourable postoperative psychosocial well-being despite similar levels of satisfaction with aesthetic outcome. CONCLUSION: We show a high degree of patient reported satisfaction by woman undergoing BRRM and reconstruction. There was a negative association with a cancer diagnosis on quality of life PROMS and higher preoperative anxiety levels negatively affected postoperative psychosocial well-being. These important findings should be part of the informed consent process during preoperative counselling.

Assessing the impact of a gynaecomastia assessment and treatment infographic in primary care in Greater Manchester.

INTRODUCTION: Men with gynaecomastia are routinely referred to breast clinics, yet most do not require breast surgical intervention. The aim of this study was to assess the impact of a novel point-of-care gynaecomastia decision infographic in primary care on the assessment, management and referral practices to tertiary breast surgical services. METHODS: A study was carried out of male patient referrals from primary care in Greater Manchester to a tertiary breast centre between January and March in 2018-2020. Referral patterns were compared before and after the infographic went live in general practices in Greater Manchester in January 2020. Data were collected for gynaecomastia referrals, including aetiology, investigation and management. RESULTS: In total, 394 men were referred to a tertiary breast centre from 163 general practices, of which 271 (68.8%) had a diagnosis of gynaecomastia. Use of the decision infographic by primary healthcare providers was associated with a decrease in male breast referrals with gynaecomastia (79.6% to 62.0%). Fewer gynaecomastia patients were referred with a benign physiological or drug-related cause after implementation of the infographic (52.2% vs 41.8%). Only 10 (3.7%) patients with gynaecomastia underwent breast surgery during the study period. CONCLUSION: Implementation of a gynaecomastia infographic in primary care in Manchester was associated with a reduction in gynaecomastia referrals to secondary care. We hypothesise that implementation of the infographic into primary care nationally may potentially translate to hundreds of patients receiving more specialty-appropriate referrals, improving overall management of gynaecomastia. Further study is warranted to test this hypothesis.

QSAR analysis of sodium glucose co-transporter 2 (SGLT2) inhibitors for anti-hyperglycaemic lead development.

QSAR (Quantitative Structure Activity Relationship) modelling was performed on a dataset of 90 sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The quantitative and explicative evaluations revealed some of the subtle and distinguished structural features that are responsible for the inhibitory potency of these compounds against SGLT2, such as less possible number of ring carbons at 8 Å from the lipophilic atoms in the molecule (fringClipo8A) and more possible value for the sum of the partial charges of the lipophilic atoms present within seven bonds from the donor atoms (lipo_don_7Bc). Multivariate GA-MLR (genetic algorithm-multi linear regression) and thorough validation methodology out-turned a statistically robust QSAR model with a very high predictability shown from various statistical parameters. A QSAR model with r2 = 0.83, F = 51.54, Q2LOO = 0.79, Q2LMO = 0.79, CCCcv = 0.88, Q2Fn = 0.76-0.81, r2ext = 0.77, CCCext = 0.85, and with RMSEtr < RMSEcv was proposed. This QSAR model will assist synthetic chemists in the development of the SGLT2 inhibitors as the antidiabetic leads.

Oncoplastic breast surgery: A guide to good practice.

Oncoplastic Breast Surgery has become standard of care in the management of Breast Cancer patients. These guidelines written by an Expert Advisory Group; convened by the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS), are designed to provide all members of the breast cancer multidisciplinary team (MDT) with guidance on the best breast surgical oncoplastic and reconstructive practice at each stage of a patient's journey, based on current evidence. It is hoped they will also be of benefit to the wide range of professionals and service commissioners who are involved in this area of clinical practice.

Residual lymph node tumour burden following removal of a single axillary sentinel lymph with macrometastatic disease in women with screen-detected invasive breast cancer.

BACKGROUND: Women with screen-detected invasive breast cancer who have macrometastatic disease on axillary sentinel lymph node biopsy (SLNB) are usually offered either surgical axillary node clearance (ANC) or axillary radiotherapy. These treatments can lead to significant complications for patients. The aim of this study was to identify a group of patients who may not require completion ANC. METHODS: Data from the NHS Breast Screening Programme between 1 April 2012 and 31 March 2017 were interrogated to identify women with invasive breast carcinoma and a single sentinel lymph node (SLN) with macrometastatic disease who subsequently proceeded to completion ANC. Univariable and multivariable analyses were performed to identify patients with a single positive SLN who had no further lymph node metastasis on ANC. RESULTS: Of the 2401 women included in the cohort, the presence of non-sentinel node disease was significantly affected by: the number of nodes obtained at SLNB (odds ratio (OR) 0.49 for retrieval of more than 1 node), invasive size of tumour (OR 1.63 for size greater than 20 mm), surgical treatment (OR 1.34 for mastectomy), human epidermal growth factor receptor (HER) 2 status (OR 0.71 for HER2 positivity), and patient age (OR 1.10 for age less than 50 years; OR 1.46 for age greater than 70 years). Patients aged less than 70 years, with tumour size smaller than 2 cm, more than one node retrieved on SLNB, and who had breast-conserving surgery had a lower chance of positive non-sentinel nodes on completion ANC compared with other patients. CONCLUSION: This study, of a purely screen-detected breast cancer cohort, identified a subset of patients who may be spared completion ANC in the event of a single axillary SLN with macrometastasis.

National Trends in Lumbar Puncture from 2010 to 2018: A Shift Reversal from the Emergency Department to the Hospital Setting for Radiologists and Advanced Practice Providers.

BACKGROUND AND PURPOSE: Prior research has shown substantial shifts in procedure shares between specialty groups providing lumbar punctures. Our aim was to analyze national trends in lumbar punctures among the Medicare population from 2010 to 2018. MATERIALS AND METHODS: Medicare Part B Physician/Supplier Procedure Summary Master Files from 2010 to 2018 were analyzed for all Current Procedural Terminology, Version 4 codes related to lumbar punctures (62270 and 62272). Lumbar puncture procedure volume and utilization rates were assessed and stratified by place of service and specialty background of the providers. RESULTS: From 2010 to 2018, the overall number of lumbar puncture procedures essentially has not changed (92,579 versus 92,533). Radiologists hold the largest and an increasing procedure share of diagnostic and overall lumbar punctures (overall share, 45.7% in 2010 [n = 42,296] versus 52.3% in 2018 [n = 48,414]). Advanced practice providers have increased their procedure share (3.7% in 2010 [n = 3388] versus 8.4% in 2018 [n = 7785], + 129.8% procedure volume). Emergency medicine physicians and neurologists have a decreasing procedure share (21.8% versus 15.3% and 12.5% versus 8.8%, respectively). The inpatient hospital setting remains the largest place of service for lumbar punctures, recording a 5.3% increase in procedure share. The emergency department lumbar puncture volume has declined, with a 7.4% decrease in the overall procedure share. Similarly, the hospital outpatient department procedure volume has increased (+4%), while the private office volume has decreased (-1.7%). CONCLUSIONS: During the past decade, lumbar puncture procedures among the Medicare population have remained stable, with a shift in procedure volume from the emergency department and private offices to the hospital setting, which has mainly affected radiologists and advanced practice providers.

Indentation and Transverse Diameter of the Meckel Cave: Imaging Markers to Diagnose Idiopathic Intracranial Hypertension.

BACKGROUND AND PURPOSE: Clinical and imaging manifestations of idiopathic intracranial hypertension should prompt early diagnosis and treatment to avoid complications. Multiple diagnostic imaging criteria are reported to suggest the diagnosis of idiopathic intracranial hypertension with questionable sensitivity and/or specificity. Increased intracranial pressure results in dilation of the perineural cisternal spaces such as the optic nerve sheaths and the Meckel cave. It may also cause protrusion of cisternal structures of the Meckel cave through the skull base foramina, which could result in indentation or a bilobed appearance of the Meckel cave. We investigated the changes in the Meckel cave in patients with proved idiopathic intracranial hypertension versus healthy controls. MATERIALS AND METHODS: We studied 75 patients with a diagnosis of idiopathic intracranial hypertension and 75 age-and sex-matched healthy controls. The transverse diameter of Meckel cave was measured in the axial and coronal planes of T2-weighted MR imaging sequences, and comparison was made between the 2 groups. RESULTS: The mean diameters of the Meckel cave on the coronal T2 plane in patients with idiopathic intracranial hypertension were 5.21 ± 1.22 mm on the right side and 5.16 ± 0.90 mm on the left side, while in the control group, they measured 3.89 ± 0.62 mm and 4.09 ± 0.68 mm, respectively (P value < .001). Of 75 patients with an approved diagnosis of idiopathic intracranial hypertension, 57 (76%) showed an indented Meckel cave as opposed to 21 (28%) in the control group. CONCLUSIONS: Our results confirm for the first time that the shape and size of the Meckel cave can be used as sensitive and specific diagnostic imaging markers for the diagnosis of idiopathic intracranial hypertension.

Extending the identification of structural features responsible for anti-SARS-CoV activity of peptide-type compounds using QSAR modelling.

A quantitative structure-activity relationship (QSAR) model was built from a dataset of 54 peptide-type compounds as SARS-CoV inhibitors. The analysis was executed to identify prominent and hidden structural features that govern anti-SARS-CoV activity. The QSAR model was derived from the genetic algorithm-multi-linear regression (GA-MLR) methodology. This resulted in the generation of a statistically robust and highly predictive model. In addition, it satisfied the OECD principles for QSAR validation. The model was validated thoroughly and fulfilled the threshold values of a battery of statistical parameters (e.g. r 2 = 0.87, Q 2 loo = 0.82). The derived model is successful in identifying many atom-pairs as important structural features that govern the anti-SARS-CoV activity of peptide-type compounds. The newly developed model has a good balance of descriptive and statistical approaches. Consequently, the present work is useful for future modifications of peptide-type compounds for SARS-CoV and SARS-CoV-2 activity.

Evaluating tisagenlecleucel and its potential in the treatment of relapsed or refractory diffuse large B cell lymphoma: evidence to date.

Chimeric antigen receptor (CAR) T cells have changed the treatment landscape of relapsed or refractory diffuse large B cell lymphoma. This review focuses on the biology of tisagenlecleucel and the clinical data that support its use in this setting. In addition, we discuss how it compares to other CAR T products, the financial implications for payers, and ongoing trials.

Axillary Surgery Following Neoadjuvant Chemotherapy - Multidisciplinary Guidance From the Association of Breast Surgery, Faculty of Clinical Oncology of the Royal College of Radiologists, UK Breast Cancer Group, National Coordinating Committee for Breast Pathology and British Society of Breast Radiology.

AIMS: These multidisciplinary guidelines aim to provide clinically helpful, evidence-based recommendations on the surgical management of the axilla in patients who have received neo-adjuvant chemotherapy for early breast cancer. MATERIALS & METHODS: Following a review of published evidence, a writing group representing all disciplines quorate within a breast cancer multidisciplinary meeting prepared the guidelines. KEY RECOMMENDATIONS: In patients presenting with clinically node negative axillae, sentinel node biopsy (SNB) may be performed prior to or on completion of neo-adjuvant chemotherapy (NACT). In patients presenting with clinically node positive axillae, SNB may be safely considered following completion of NACT. Four nodes should be removed with dual mapping. If evidence of complete pathological response of previous metastases is seen, axillary radiotherapy may be offered. If residual cancer (isolated tumour cells, micro- or macrometastes) is seen within the SNB, offer axillary node dissection.

Blocking FcRn in humans reduces circulating IgG levels and inhibits IgG immune complex-mediated immune responses.

The neonatal crystallizable fragment receptor (FcRn) functions as an intracellular protection receptor for immunoglobulin G (IgG). Recently, several clinical studies have reported the lowering of circulating monomeric IgG levels through FcRn blockade for the potential treatment of autoimmune diseases. Many autoimmune diseases, however, are derived from the effects of IgG immune complexes (ICs). We generated, characterized, and assessed the effects of SYNT001, a FcRn-blocking monoclonal antibody, in mice, nonhuman primates (NHPs), and humans. SYNT001 decreased all IgG subtypes and IgG ICs in the circulation of humans, as we show in a first-in-human phase 1, single ascending dose study. In addition, IgG IC induction of inflammatory pathways was dependent on FcRn and inhibited by SYNT001. These studies expand the role of FcRn in humans by showing that it controls not only IgG protection from catabolism but also inflammatory pathways associated with IgG ICs involved in a variety of autoimmune diseases.

NHS Breast Screening multidisciplinary working group guidelines for the diagnosis and management of breast lesions of uncertain malignant potential on core biopsy (B3 lesions).

Needle core biopsy is considered the histological diagnostic method of choice for screen-detected breast lesions. Although the majority are definitively diagnosed as normal, benign, or malignant, approximately 7% are categorised as B3, of uncertain malignant potential. These include a wide range of lesions with different risks of associated malignancy from <2% to approaching 40% from literature review in UK practice. Historically, these have typically been surgically excised as a diagnostic procedure but the majority are then proven to be benign. An alternative approach, for many of these lesions, is thorough sampling/excision by vacuum-assisted biopsy techniques to exclude the presence of co-existing carcinoma. This would potentially reduce the benign open biopsy rate whilst maintaining accuracy of cancer diagnosis. A group from the Radiology, Surgery, and Pathology NHS Breast Screening Programme Co-ordinating Committees and an additional co-opted expert were charged with review and development of guidelines for the clinical management of B3 lesions. The guidelines reflect suggested practice as stated by the NHS Breast Screening Programme and approved by the Royal College of Radiologists.

Renal Biopsy in Paroxysmal Nocturnal Hemoglobinuria: An Insight into the Spectrum of Morphologic Changes.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, potentially life-threatening disease of blood, characterized by complement-induced intravascular hemolytic anemia and thrombosis. PNH can sometimes present directly with renal manifestations, without showing any hematological manifestation. It, therefore, becomes essential for clinicians and pathologists to be aware of the spectrum of renal changes in PNH. The aim of this study was to document the morphologic changes observed in renal biopsies in patients with PNH. This is an observational study. We report three cases that presented with acute or chronic renal insufficiency and were suspected as PNH on viewing their renal biopsy in light of their clinical and laboratory details. All the three cases were confirmed as PNH on the basis of flow cytometric analysis of CD55 and CD59. Renal biopsy in these patients showed a variety of morphologic changes, however the most consistent finding was moderate-to-heavy siderosis in their kidneys. PNH per se may be difficult to diagnose clinically and sometimes present directly with renal manifestations. It is, therefore, prudent for nephrologists and nephropathologists to be aware of the spectrum of renal changes in PNH.