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Conventional tissue sampling can lead to misdiagnoses and repeated biopsies. Additionally, tissue processed for histopathology suffers from poor nucleic acid quality and/or quantity for downstream molecular profiling. Targeted micro-sampling of tissue can ensure accurate diagnosis and molecular profiling in the presence of spatial heterogeneity, especially in tumors, and facilitate acquisition of fresh tissue for molecular analysis. In this study, we explored the feasibility of performing 1–2 mm precision biopsies guided by high-resolution reflectance confocal microscopy (RCM) and optical coherence tomography (OCT), and reflective metallic grids for accurate spatial targeting. Accurate sampling was confirmed with either histopathology or molecular profiling through next generation sequencing (NGS) in 9 skin cancers in 7 patients. Imaging-guided 1–2 mm biopsies enabled spatial targeting for in vivo diagnosis, feature correlation and depth assessment, which were confirmed with histopathology. In vivo 1-mm targeted biopsies achieved adequate quantity and high quality of DNA for next-generation sequencing. Subsequent mutational profiling was confirmed on 1 melanoma in situ and 2 invasive melanomas, using a 505-gene mutational panel called Memorial Sloan Kettering-Integrated mutational profiling of actionable cancer targets (MSK-IMPACT). Differential mutational landscapes, in terms of number and types of mutations, were found between invasive and in situ melanomas in a single patient. Our findings demonstrate feasibility of accurate sampling of regions of interest for downstream histopathological diagnoses and molecular pathology in both in vivo and ex vivo settings with broad diagnostic, therapeutic and research potential in cutaneous diseases accessible by RCM-OCT imaging.

Introduction: Rational use of drugs against most common and life‑threatening tropical diseases such as malaria remains a huge challenge, particularly in sub-Saharan African region. The correct use of antimalarial drugs is the key not only to therapeutic success but also to deterring the spread of drug resistance malaria. Aims: To assess the physicians’ compliance with the national anti’-malaria treatment guidelines among Under five (U-5) years children in secondary health facilities in Sokoto metropolis. Methods: This was a cross-sectional study conducted as an exit interview among 292 mothers/caregivers of febrile U-5 children with antimalarial prescription, that presented to the out-patient clinics of the selected secondary health facilities in Sokoto metropolis. Simple random sampling technique using balloting option was used to select 2 secondary Health facilities in the metropolis, Proportionate allocation was done to allocate study subjects to the selected Health facilities based on average weekly outpatient attendance. The data was collected using an interviewer-administered questionnaire. Descriptive statistics was used to analysed data using IBM SPSS version 22. Results: Of the 292 children, only 115(39.4%) had malaria parasite test requested by the physician, out of which 63(54.8) had microscopy, while 52(45.2) of the children had malaria Rapid Diagnostic Test (mRDT). One hundred and eighty-five (65.1%) of the children were treated presumptively with anti-malarial drugs. Artemisinin based Combination Therapy (ACT) was prescribed in 221(77.8%) of the under-fives. The commonest prescribed ACT was Artemether-Lumefantrine in 113(77.4%) of the children. Majority 263(92.6%) of the prescriptions were in brand names. Recommendation: The physicians’ compliance with national malaria treatment guidelines using the proportion of U-5 children was suboptimal. There was over prescription of anti-malarial drugs, as majority of the patients treated for malaria had no laboratory evidence for the treatment. However, compliance with the use of ACT was good. This study shows also suboptimal compliance with WHO prescribing indicators with respect to prescription in generic names. Regular training of the health care providers by the government is recommended to improve adherence to antimalarial treatment guideline.

Background: Substance use is a global public health problem with increasing burden among university students. This study assessed the prevalence, pattern and risk factors of substance use among undergraduate students of Afe Babalola University, Ado-Ekiti, Nigeria.Methods: This was a cross-sectional study of undergraduate students of Afe Babalola University, Ado-Ekiti. A multi-stage sampling technique was used to select respondents. Data collection tool was a structured self-administered questionnaire. Data analysis was done using Statistical Package for the Social Sciences (SPSS) version 23. Statistical significance was set at p value

In this study, photon attenuation parameters of (30-x) SiO2–15PbO–10CdO-xTiO2, with x = 0, 2, 4, 6, 8 and 10% mol, were determined and their application as shielding material were discussed. The WinXCOM software was used to determine the mass attenuation coefficient of the studied glasses for the energy range (0.015-15MeV). The mass attenuation coefficient of the glass samples first decline up to 0.09 MeV and slightly increase abruptly and then declined uniformly for all the glasses to approximately zero after about 10 MeV. The effective atomic number (Zeff) was also calculated for the glass samples and were observe to raise from 0.015 to 0.02 MeV and then decreased between 0.02-5 MeV. On account of the dominance of the photoelectric effect in the low energy region, there was a sudden increase in Zeff at about 0.08 MeV close to the absorption edge of the Pb (0.088 MeV). The rapid increment was observed at 0.1–1.5 MeV by transcending typical Compton scattering interaction at intermediate energies for Zeff'’s and began to decrease in the same form again. The lower Zeff values were found in low and high energy region for all SPCT glasses. The calculated mean free path, half value layer and tenth value layer values were observe to decline as the TiO2 doping of the glasses increased which accounts for the three photon interaction mechanisms effectiveness in the variation of MFP and HVL values with energy. It can be concluded that SPCT glasses may be considered an alternative material for radiation shielding practices.

Sentinel lymph node biopsy (SLNB) is often omitted in selected patients with advanced primary melanoma, although the justification/criteria for omission have been debated. We sought to determine whether assessment of frailty could serve as an objective marker to guide selection for SLNB in patients with advanced primary melanoma. Patients presenting with clinical stage IIC (ulcerated, > 4 mm Breslow thickness) cutaneous melanoma from January 1999 through June 2019 were included. Frailty was assessed using the Memorial Sloan Kettering Frailty Index (MSK FI), a composite score of functional status and medical comorbidities. Five-year melanoma-specific survival (MSS) and overall survival (OS) were estimated using Cox regression, and predictors of OS were identified using competing risk models. MSS did not differ between patients who did (n = 451) or did not undergo SLNB (n = 179) [63.2% vs. 65.0%, p = 0.14]; however, omission of SLNB was associated with decreased 5-year OS (29% vs. 44%, p

Vegetables in Cambodia are commonly sold in informal markets lacking food safety standards and controls. Currently, data on microbial contamination of vegetables in Cambodian informal markets are limited. The purpose of this study was to investigate Salmonella enterica and indicator organisms (generic Escherichia coli and coliforms) on the surface of fresh vegetables sold in informal markets in Cambodia. A sample of loose-leaf lettuce, tomatoes, and cucumbers were collected from 104 vendors at four informal markets in Battambang and Siem Reap provinces during rainy and dry seasons. Detection methods for Salmonella enterica were adapted from the Food and Drug Administration's Bacteriological Analytical Manual (FDA BAM). Quantification of coliforms and generic E. coli populations was conducted by plating onto E. coli/Coliform count plates. Salmonella enterica was most prevalent on lettuce during the dry season (56.5%, 95% CI [41.0, 70.8]) compared to the rainy season (15.4 95% CI [7.5, 29.1]), whereas no significant seasonal differences were apparent for tomatoes and cucumbers. Regardless of season, levels of Salmonella enterica were highest on lettuce (5.7 log CFU/g, 95% CI [5.5, 5.9]), relative to cucumbers (4.2 log CFU/g, 95% CI [3.8, 4.6]) and tomatoes (4.3 log CFU/g, 95% CI [4.1, 4.6]). For generic E. coli, prevalence was higher during the rainy season (34.0%, 95% CI [25.4, 43.8]) as compared to the dry season (9.1%, 95% CI [4.9, 16.5]), with the highest prevalence estimated on lettuce. Similarly, the level of coliforms on lettuce and tomatoes was greater during the rainy season (6.3 and 5.3 log CFU/g, 95% CI [5.7, 6.8] and [4.7, 5.8], respectively), relative to the dry season (5.2 and 3.9 log CFU/g, 95% CI [4.7, 5.7] and [3.4, 4.4], respectively). In summary, these results indicate seasonal patterns for microbial prevalence in lettuce, and an overall high level of bacterial contamination on raw vegetables sold in Cambodian informal markets.

Background: Diabetes places extra-burden on those affected with the condition particularly in resource constraint settings. Inaccessibility to affordable diagnostic procedures poses a major challenge to the assessment of cardiovascular status in patients with type-2 diabetes in resource limited settings. The study was aimed at evaluating some easily accessible biochemical markers and anthropometric indices implicated in cardiovascular disease amongst T2DM patients.Methods: One hundred and sixty (160) type-2 diabetic patients grouped into type-2 diabetes only as group 1, type-2 diabetic patients diagnosed with hypertension as group 2, and eighty (80) age and sex-matched controls as group 3, were enrolled in a cross-sectional pattern. Biochemical parameters were assayed using standard laboratory methods. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 20.0 with statistical significance considered at p≤0.05.Results: The values obtained for diabetic groups were: Glycated Hemoglobin (HbA1c) 9.07±1.99, 10.15±4.98, Total Homocysteine (tHcy) 14.85±52.10, 28.35±100.35, high sensitivity C-reactive protein (hs-CRP) 6.72±6.78,10.00±11.15, Waist Circumference, 92.58±1.55, 93.65±18.91, Hip Circumference, 96.87±9.01, 98.96±20.33, Systolic Blood Pressure, 113.50±12.94, 135.50±22.72, Diastolic Blood Pressure, 70.75±8.57, 75.38±12.62, Body Mass Index, 25.40±4.70, 26.93±6.50 (among patients) and HbA1c 5.81±0.86, tHcy 0.75±1.44, hs-CRP 5.30±6.19, Waist Circumference 83.15±10.69, Hip Circumference 93.50±22.05, Systolic Blood Pressure, 113.50±10.20, Diastolic Blood Pressure, 77.00±7.19, Body Mass Index, 24.84±4.93 (among controls).Conclusion: The assessment of some cardio metabolic markers and anthropometric indices may provide easy and accessible tools for prediction and assessment of cardiovascular disease in patients with T2DM especially in resource poor settings.Annals of Medical Laboratory Science (2021) 1(1), 36 - 48

Introduction: Prescription practices for malaria have been shown to influence the emergence of resistance to antimalarial drugs. Appropriate antimalarial drug use contributes to reductions in morbidity and mortality due to malaria with a consequent socioeconomic benefit, thus the success of a new malaria treatment policy would depend on the adherence of health care providers and patients to treatment recommendations. This study aimed to determine the prescribing pattern of anti-malaria in primary health care facilities in Sokoto State. Methods: A cross sectional study was carried-out in the Primary Health Care facilities in Sokoto State. Screening of prescription forms from the patients who presented at the outpatient clinic during the period of the study in the selected health facilities was done at the point of exit, and only those with antimalarial prescription were consecutively selected. An interviewer administered questionnaire was used to obtained brief history of the illness among 276 respondents who were enrolled in to the study. Record of Rapid Diagnostic Test (mRDT) for the diagnosis of the malaria was obtained from the patients and or their caregivers. Data were analyzed using IBM® SPSS version 20 statistical packages. Results: Majority 85 (30.8%) of the respondents were aged ≤ 1-10 years followed by 21-30 years 81 (29.3) Of the 276 antimalarial prescription forms obtained from the respondents, artemisinin- based combination therapy (ACT) was 166 (60.1%) and monotherapy was 110 (39.9%). The commonest artemisinin-based combination therapy prescribed for the respondents was Artemether-Lumefantrine 141 (84.9%) followed by Artesunate- Amodiaquine 16 (9.6%). The commonest oral mono-therapy prescribed was Sulphadoxine-pyrimethamine 28 (75.7%) while the most prescribed injectable monotherapy was artemether 59 (80.8%). Rapid Diagnostic Test for malaria (mRDT) was done for 274 (99.3%) respondents; those with mRDT positive were 238 (86.9%). The commonest presenting symptoms was fever 274 (99.3%) flowed by headache 225 (80.7%) and loss of appetite 215 (77.9%). Conclusion: The pattern of antimalarial prescription observed in this study was mainly artemisinin-based combination therapy. However, antimalarial monotherapy is still being prescribed. There is need for regular training of the health care workers on the appropriate treatment of malaria using the national guideline for treatment of malaria. Regular supply and availability of ACTs in all health facilities across the state will ensure full compliance with national guideline for malaria treatment using ACTs.

Surgical resection is the treatment for early cutaneous melanoma and is often curative. Some patients, however, will subsequently relapse. High-risk features in the primary tumor and regional lymph node metastasis highlight patient subsets that are at increased risk for recurrent disease. Immunotherapy in the form of checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab have been shown to improve recurrence-free survival for node-positive melanoma in the adjuvant setting and will be the focus of this review.

The consumer price for poultry products in Nigeria and the expansion of the commercial poultry industry are negatively affected by the utilization of competitive and costly ingredients in making poultry diets. Consequently, the identification and utilization of locally available alternatives would greatly reduce cost of poultry production and products. In this regard, a study was undertaken to examine the effects of replacement of yellow maize (YM) with gayamba pearl millet variety as dietary energy source on carcass yield and blood parameters of broiler chickens. Three hundred (300) Ross 308 broiler chicks weighing 167.94 – 173.07g were randomly assigned to four dietary treatments of 75 birds each. Each treatment was replicated thrice with 25 birds in a completely randomized design. The experimental diets contained 0, 33.33, 66.67 and 100% gayamba millet as replacement for YM designated as diets 1, 2, 3 and 4 respectively. Full-fat soya bean and groundnut cake meal were the main vegetable protein sources used in the diets. Feed and water were provided ad libitum and the experiment lasted for 49 days. Results for carcass yield indicated a significant (P

Postoperative analgesic effects of tramadol and diclofenac in goats presented for diaphyseal femoral fracture management were compared. Eight adult goats aged 10 to 24 months (16±5.2 months) were used. The first group of 4 goats received 3 mg/kg of tramadol intramuscularly (IM), and 2.5 mg/kg of diclofenac sodium was administered to the second group of 4 goats before induction of anesthesia IM. Mechanical pain scores, clinico-physiological and red and white blood cell counts were evaluated over a period of twelve hours post drug administration. The study groups were not revealed to the postoperative pain assessors until the end of the study. There was no significant difference in the rectal temperature values and the analgesiometer readings between the tramadol and diclofenac groups (p

Optical filters used specifically for special functions to block a particular wavelength or range of wavelength and transmit the rest of the spectrum have received research attention for the past few eras. Recently, optical filter based on multilayer coating are more focused due to potential to manipulate filter properties by changing layer thickness in order to apply in various fields. This Quarter wave stack (QWS) model design is one of the approaches to design optical filter such as edge filter. However, to obtain desire minimum specification need an optimization. Therefore, in this study aims to design optical edge filter based QWS model by optical matrix method in Octave software. In this design, MoS2 and Si are being choose for high (H) and low (L) refractive index materials respectively. The optimum twenty-four (24) number of layers are determined by calculating maximum transmittance obtained. The Rayleigh wavelength ( λex ) of 405 nm ,532 nm and 633 nm are selected and ‘glass|12HL|air’ configuration is set for the design simulation. Then, the cut-on wavelength (λcut-on) and cut-off wavelength ((λcut-off) of successful designed optical edge filter are measured. The result shows that the cut-on wavelength of 408.11 nm, 536 nm and 640.25 nm with minimum effective transmission (MET) of 32.3%, 31.3% and 32% respectively are obtained. In conclusion, this present study shows the deviation between the calculated value and simulation of about 0.2 nm,1.7 nm and 1.15 nm for each λex of 405 nm, 532 nm and 633 nm is determined. But for λcut-off, the value obtained are much higher than the calculated value. The MET of each filter is 32.3% ,31.3% and 32% for Rayleigh wavelength respectively.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

One of the major developments in the technology today is the wind turbine that generates electricity and feed it directly to the grid which is used in many part of the world. The main purpose of this work is to determine the wind potential for electricity generation in Aliero, Kebbi state. Five years Data (2014-2018) was collected from the metrological weather station (Campell Scientific Model), the equipment installed at Kebbi State University of Science And Technology Aliero The data was converted to monthly and annual averages, and compared with the threshold average wind speed values that can only generate electricity in both vertical and horizontal wind turbines. The highest average wind speed 2.81 m/s was obtained in the month of January and the minimum average wind speed of 1.20 m/s in the month of October. Mean annual wind speed measured in the study area shows that there has been an increase in the wind speed from 2014 which peaked in 2015 and followed by sudden decrease to a minimum seasonal value in the year 2016. The highest wind direction is obtained from the North North-East (NNE) direction. From the results of wind power density it shows that we have highest wind power density in month of January and December with 0.8635 w/ m2 and 0.8295 w/ m2 respectively, while lowest wind power density in the month of October and September with 0.6780 w/ m2 and 0.6575 w/ m2 respectively. Result of the type Wind Turbine to be selected in the study area shows that the site is not viable for power generation using a horizontal wind turbine but the vertical wind turbine will be suitable for the generation of electricity.

INTRODUCTION: Checkpoint inhibitors have improved outcomes in metastatic melanoma, with 4-year overall survival (OS) of 46% for anti-PD-1 alone or 53% in combination with anti-CTLA-4. However, the median progression free survival is 6.9 and 11.5 months, respectively. Many who progress have gone on to alternative treatments, including surgery, yet the outcome of patients selected for surgery after checkpoint blockade remains unclear. METHODS: Patients who were treated with checkpoint blockade from 2003 to 2017, followed by metastasectomy, were identified from a prospectively maintained institutional melanoma database. Response to immunotherapy was assessed at the time of surgery. Patients were categorized as having responding, isolated progressing, or multiple progressing lesions. RESULTS: Of the 237 total patients identified, 208 (88%) had stage IV disease and 29 (12%) had unresectable stage III disease at the start of immunotherapy. Median OS following first resection was 21 months. Median follow-up among survivors was 23 months. Complete resection at the first operation (n=87, 37%), was associated with improved survival compared with patients with incomplete resection (n=150, 63%) (median OS not reached (NR) versus 10.8 months, respectively; 95% CI: 7.3,14.8; p

Background: While harmaline has been used as a pharmacological model of essential tremor (ET) in rodents and pigs, less is known about the effects of this pharmacological treatment in awake-behaving non-human primates. In this study, we investigated the time-course, amplitude, frequency, and consistency of harmaline tremor in primates. Methods: Three rhesus macaques were administered doses of harmaline ranging from 2–12 mg/kg (i.m.), and tremorous movements were quantified with accelerometers. One subject was also trained to perform a self-paced cued reaching task, with task engagement assessed under harmaline doses ranging from 2–8 mg/kg (i.m.). Results: Whole-body tremors manifested within 30 minutes of threshold-dose administration, and peak oscillatory frequency ranged between 10–14 Hz. However, large differences in tremor intensity and intermittency were observed across individual subjects under similar dosing levels. Additionally, engagement with the reaching task was dependent on harmaline dose, with performance mostly unaffected at 2 mg/kg and with little task-engagement at 8 mg/kg. Discussion: We provide a detailed assessment of factors that may underlie the heterogeneous responses to harmaline, and lay out important caveats towards the applicability of the behaving harmaline-tremoring non-human primate as a preclinical model for ET. Highlights The harmaline-primate is revisited for its potential as a preclinical model of tremor. Spontaneous tremor was heterogenous in amplitude across subjects despite similar harmaline doses, action tremors were not consistently observed, and performance on a behavioral task degraded with higher dosages.

Background For many years now, inguinal hernia repair in children has been done either by the open approach or laparoscopically with laparoscopy having the edge in terms of cosmesis and postoperative pain. However, recent studies have called for a return of the open approach as it had a comparable result to laparoscopy with lesser cost. This study aims to compare the outcomes of the two approaches at our institution. Methods This is a retrospective analysis of the prospectively collected data of all patients aged between 6 months and 13 years who underwent open or laparoscopic inguinal hernia repair in the period between January 2017 and July 2019 at our institution. Results 155 patients were included in the study. 100 (64.5%) underwent open inguinal repair while 55 (35.5%) were done laparoscopically. There was no significant difference in the postoperative complications between the open and laparoscopic groups (P = 0.66). The overall mean operative time for the laparoscopic group and the open group is (45.7 ± 15.2, 45.5 ± 15.4 min, P = 0.83) respectively. However, a subgroup analysis showed a statistical difference in the operative time in bilateral hernias favoring the laparoscopic approach, (44 ± 13.2, 63.2 ± 26.4 min respectively, P = 0.049). Laparoscopy was also associated with shorter times to full recovery compared to the open group (4.7 days, 7.5 days, P = 0.013). Surprisingly, there was no difference in the cosmetic outcome between the two groups which is contrary to the published literature. Conclusions Laparoscopic inguinal hernia repair in children is a feasible and reproducible procedure. It permits the evaluation of the contralateral groin without further incisions. In our study, laparoscopy was superior in terms of operative time in bilateral hernias and the time to recovery. Finally, an added benefit to laparoscopy is that it offers more training opportunities for fellows and residents to improve their laparoscopic skills., Highlights • Laparoscopic inguinal hernia repair in children is a feasible and reproducible procedure. • Laparoscopy was superior in terms of operative time in bilateral hernias and the time to recovery. • Laparoscopic hernia repair in children offers more training opportunities for fellows and residents to improve their laparoscopic skills.

Background Pneumococcal disease contributes significantly to childhood morbidity and mortality and treatment is costly. Nigeria recently introduced the Pneumococcal Conjugate Vaccine (PCV) to prevent pneumococcal disease. The aim of this study is to estimate health provider and household costs for the treatment of pneumococcal disease in children aged Methods We recruited U5s with clinical pneumonia, pneumococcal meningitis or pneumococcal septicaemia from a tertiary and a secondary level hospital in Kano, Nigeria. We obtained resource utilisation data from medical records to estimate costs of treatment to provider, and household expenses and income loss data from caregiver interviews to estimate costs of treatment to households. We defined catastrophic health expenditure (CHE) as household costs exceeding 25% of monthly household income and estimated the proportion of households that experienced it. We compared CHE across tertiles of household income (from the poorest to least poor). Results Of 480 participants recruited, 244 had outpatient pneumonia, and 236 were hospitalised with pneumonia (117), septicaemia (66) and meningitis (53). Median (IQR) provider costs were US$17 (US$14-22) for outpatients and US$272 (US$271-360) for inpatients. Median household cost was US$51 (US$40-69). Overall, 33% of households experienced CHE, while 53% and 4% of the poorest and least poor households, experienced CHE respectively. The odds of CHE increased with admission at the secondary hospital, a diagnosis of meningitis or septicaemia, higher provider costs, and caregiver having a non-salaried job. Conclusion Provider costs are substantial, and households incur treatment expenses that considerably impact on their income and this is particularly so for the poorest households. Sustaining the PCV programme and ensuring high and equitable coverage to lower disease burden will reduce the economic burden of pneumococcal disease to the healthcare provider and households. What is already known? Children Pneumococcal conjugate vaccine (PCV) was introduced in Nigeria in 2016 to reduce the burden of pneumococcal disease PCV is currently subsidised through Gavi financial support and Nigeria will transition to full self-financing in a few of years There is no contextual evidence in Nigeria on economic burden of IPD to the health system and society that can support longer term investments in PCV when Gavi co-financing terminates What are the new findings? Treatment of one hospitalised episode of pneumococcal disease cost on average, US$300 to the provider, and US$83 to the household with significant variation by clinical syndrome and level of care Overall, a third of the households encountered costs that were catastrophic (i.e., >25% of household income) Burden of CHE varied by household income tertile ranging from 4% in the least poor households (highest income tertile) to 53% in the poorest households (lowest income tertile) Despite the short illness duration, pneumococcal disease syndromes result in huge economic costs to providers and households What do the new findings imply? Sustaining the PCV programme and achieving high PCV coverage has the potential of saving resources at both provider and household level Households are at risk of further impoverishment from catastrophic expenses associated with treatment of pneumococcal disease. This risk can also be significantly reduced by PCV.

Castration is a common management procedure employed in North American cattle production and is known to cause a pain response. The present study was designed to investigate the effect of unmitigated surgical castration on the electroencephalography (EEG) responses and plasma substance P (SP) concentrations in calves of different ages under the same experimental conditions. Thirty male Holstein calves in three age categories [&lt, 6 weeks (6W), 3 months (3M), 6 months (6M), 10 calves per age group] were used in the study. Calves were subjected to a simulated castration session (SHAM) followed 24 h later by surgical castration (CAST) without analgesia. An EEG analysis was performed before the procedure (i.e., baseline), at treatment, and 0–5, 5–10, and 10–20 min post-treatment for both SHAM and CAST, respectively. Blood samples were collected immediately prior to both treatments (time 0) and again at 1, 2, 4, 8, and 12 h after both treatments. The EEG results showed a three-way interaction between treatment, age, and time for delta and beta absolute power, beta relative power, total power, and median frequency (p = 0.004, p = 0.04, p = 0.04, p = 0.03, and p = 0.008, respectively). Following CAST, EEG total power decreased, and median frequency increased relative to SHAM in 6W and 3M calves only following treatment. For 6W and 3M calves, delta and beta absolute power increased at CAST and at later time points relative to SHAM. Marginal evidence for two-way interactions was noted between time and treatment and between age and treatment on the concentration of SP (p = 0.068 and p = 0.066, respectively). Substance P concentrations decreased in CAST treatment compared to SHAM at the later times (8 h: p = 0.007, 12 h: p = 0.048), 6W calves showed lower SP concentration at CAST relative to SHAM (p = 0.017). These findings indicate variation in EEG responses and in SP concentrations following unmitigated surgical castration in calves and that these responses may be age specific. These EEG findings have implications for supporting the perception of the pain associated with surgical castration in young calves and emphasize the urgency of pain mitigation strategies during routine husbandry practices such as castration, as typically implemented in North American cattle management.

Author(s): Guo, Y; Ahn, M-J; Chan, A; Wang, C-H; Kang, J-H; Kim, S-B; Bello, M; Arora, RS; Zhang, Q; He, X; Li, P; Dechaphunkul, A; Kumar, V; Kamble, K; Li, W; Kandil, A; Cohen, EEW; Geng, Y; Zografos, E; Tang, PZ | Abstract: BackgroundTreatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries.Patients and methodsIn this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation.ResultsA total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (l1% versus 5%) and leukopenia (0% versus 5%).ConclusionsConsistent with the phase III LUX-Head a Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC.Clinical trial registrationClinicalTrials.gov identifier: NCT01856478.

Background Primary effusion lymphoma (PEL) is a rare type of non-Hodgkin lymphoma. The limited disease-free survival after chemotherapy has resulted in a poor prognosis. The outcomes data for high-dose therapy followed by autologous hematopoietic cell transplantation (auto-HCT) for PEL are limited owing to the rarity of the disease. Patients and Methods The present study included 9 patients with PEL from 2 major academic centers. Of these patients, 4 had received auto-HCT after high-dose therapy. Of the 9 patients, 8 (89%) had immunodeficiency (7 with human immunodeficiency virus seropositivity; 1, a solid organ transplant recipient) at the diagnosis. Human herpesvirus-8 by immunohistochemistry was positive in 8 patients. Anthracycline-based combination chemotherapy was used as first-line treatment in 7 patients; 4 underwent auto-HCT after attaining first complete remission. Results The median follow-up of the surviving patients was 25 months (95% confidence interval [CI], 8%-29%). The 2-year progression-free and overall survival for the 8 patients who had received treatment was 58% (95% CI, 22%-95%) and 73% (95% CI, 41%-100%), respectively. The 2-year progression-free and overall survival for the patients who had received auto-HCT was 50% (95% CI, 1%-99%) and 75% (95% CI, 33%-100%), respectively. Of the 4 auto-HCT recipients, all had been in first complete remission at the time of autografting. The cumulative incidence of relapse was 50% (95% CI, 19%-100%). No deaths were attributable to auto-HCT at 2 years after autografting. Conclusion Despite the small sample size, our data have shown that consolidative auto-HCT is safe and effective and should be considered for eligible patients with PEL after demonstration of an objective response to induction chemotherapy. However, the high relapse rate remains a concern and warrants the development of new strategies to mitigate post-transplantation relapse.

Microfluidics is an appealing analytical tool in the global effort to close the nuclear fuel cycle. Using a microfluidic chip permits the analysis of greatly reduced sample volumes compared to what is necessary for traditional analytical methods. There is a commensurate reduction in disposal volume and cost. The development of novel sensors is necessary to take full advantage of the microchip configuration, where optical-spectroscopy-based approaches offer a powerful route to characterize chemical composition. This study uses simultaneously applied UV-vis and micro-Raman spectroscopies adapted to function on the microscale to analyze in situ both the Nd3+ (UV-vis-active) and HNO3 (Raman-active) concentrations in the same sample. An adjustable translation platform was designed to hold the micro-Raman probe above and perpendicular to the chip face and the UV-vis probe in the plane of the chip. These complimentary spectral techniques when processed through multivariate partial least-squares (PLS) models gave an accurate picture of the widely varying solution concentrations as a function of time for each solution component. Solution matrix effects can drastically alter analyte signatures as measured by both UV-vis absorbance and Raman spectroscopy. PLS methods successfully modeled these spectral changes and accurately measured concentrations of components of interest within the microfluidic chip.

Objective: Pancreatic β-cell dysfunction is described to be present at the diagnosis of type 2 diabetes mellitus (T2DM) and progressively deteriorated with disease duration. However, its progression is variable and potentially influenced by several factors. The Magnesium (Mg) deficiency mediates insulin resistance but reports regarding its role in pancreatic β-cell dysfunction are scarce and conflicting. The aim of this study was to evaluate Mg deficiency effect on pancreatic β-cell function in T2DM patients at a specialist hospital in north eastern Nigeria. Materials and Methods: Study subjects were categorized in to two groups according to plasma Mg levels; 34 subjects with hypomagnesemia and 45 subjects with normal magnesium levels. Fasting blood samples were analyzed for Mg, glucose and insulin. Pancreatic β-cell function was estimated as HOMA-β. Results: Degree of pancreatic β-cell function, as measured by HOMA-β, was significantly lower among T2DM subjects with hypomagnesemia compared to the subjects with normal magnesium levels (38.1± 5.5 vs. 41.2± 6.2, Pvalue< 0.05). Lower plasma Mg was associated with decreased pancreatic β-cell function among the study subjects independent of age, BMI and duration of diabetes. Conclusion: We concluded that among subjects with T2DM in this study, Mg deficiency might be linked with worsening of pancreatic β-cell function.

The objective of this study was to compare the field growth performance of Moringa oleifera and Moringa ovalifolia in semi-arid environment of central Namibia rangeland. This part of Namibia has both arid and semi-arid climates. These climates require the growing of drought-resistant fodder trees to aid in the provision of animal feed or supplement. This is paramount to livestock farmers who are striving to meet the feed demand of their animals especially during winter and drought periods. It is upon this background that both Moringa species were grown to evaluate their field growth performances. Moringa oleifera grew faster with 224.9 cm and 281.45 cm heights than Moringa ovalifolia that had 77.025 cm and 113.2 cm heights in 2014/2015 summer season (October 2014 to April 2015) and 2015/2016 summer season (October 2015 to April 2016), respectively, although Moringa ovalifolia is native to Namibia. In Namibia, summer usually starts October and ends April the follow year after which winter follows. Moringa oleifera grew significantly higher (P < 0.05) in heights compared to Moringa ovalifolia, though they belong to the Moringaceae family and were grown under the parallel conditions. Therefore, Moringa oleifera would serve as a better alternative for improving rangelands’ productivity under these adverse climatic and environmental conditions since it can grow faster than Moringa ovalifolia, whose characteristic leads to the rapid establishment of trees and large quantity of leaf-biomass production.

BACKGROUND: Insulinomas are the most common tumour of the endocrine pancreas in dogs. These are malignant tumours with a high metastatic rate and limited efficacious chemotherapeutic options available. Recent literature supports the use of the multi-receptor tyrosine kinase inhibitor sunitinib malate for treatment of metastatic insulinoma in people. Toceranib phosphate is a veterinary targeted therapy that may provide benefit in treatment of canine insulinomas. The primary objectives of this study were to describe the duration of clinical benefit, defined as absence of clinical signs associated with hypoglycemia and/or measurable response according to the response evaluation criteria for solid tumours in dogs (cRECIST), and measures of outcome, namely progression free interval (PFI) and overall survival time (OST) in dogs diagnosed with insulinoma treated with toceranib. A secondary objective was to describe the adverse effects of toceranib in dogs with insulinoma.RESULTS: A medical record search identified 30 dogs diagnosed with insulinoma and treated with toceranib at five university hospitals and eight veterinary specialty referral hospitals. A majority (66.7%) of dogs with measurable disease experienced either complete response (CR), partial response (PR), or stable disease (SD) with toceranib therapy. The overall median progression free interval (PFI) was 561 days (95% confidence interval: [246, 727 days]). The overall median survival time (OST) was 656 days [310, 1045 days]. Larger dogs were at increased risk for disease progression (P = 0.0310) and death (P = 0.0064), with every 1 kg increase in body weight resulting in hazard ratios (HRs) of 1.045 [1.003, 1.084] and 1.05 [1.012, 1.090], respectively. In addition, time to disease progression was associated with use of therapies prior to toceranib (P = 0.0050) and type of veterinary practice (P = 0.0025). The most common adverse events with toceranib therapy were grade 1 or 2 gastrointestinal toxicities.CONCLUSIONS: Clinical benefit was reported in the majority of dogs diagnosed with insulinoma treated with toceranib, but randomized, prospective studies are needed to assess and quantify the effect of this therapy. The most commonly observed adverse events (AEs) were gastrointestinal AEs.

Background and objective Experimental models suggest the use of different therapy protocols in rheumatoid arthritis (RA) as modulators on periodontal condition. This study evaluated the effects of conventional drug treatment and anti-TNF therapy in patients with RA on microbiological and periodontal condition, establishing the association of markers of periodontal infection with indexes of rheumatic activity. Materials and methods One hundred seventy nine individuals with RA were evaluated (62 with anti-TNF-. and 115 with only DMARDs). The periodontal evaluation included plaque and gingival indexes, bleeding on probing (BOP), clinical attachment loss (CAL), pocket depth (PD) and subgingival plaque samples for microbiological analysis. Rheumatologic evaluations included a clinical examination, rheumatoid factor (RF), antibodies against cyclic-citrullinated peptides (ACPAs), and activity markers (DAS28-ERS), high sensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR). Results Anti-TNF-alpha therapy influenced periodontal microbiota with a higher frequency of T. denticola (p=0.01). Methotrexate combined with leflunomide exhibited a higher extension of CAL (p=0.005), and anti-TNF-alpha therapy with methotrexate was associated with a lower extension of CAL (p=0.05). The use of corticosteroids exerted a protective effect on the number of teeth (p=0.027). The type of DMARD affected P. gingivalis, T. forsythia and E. nodatum presence. Elevated ACPAs titers were associated with the presence of red complex periodontal pathogens (p=0.025). Bleeding on probing was associated with elevated CPR levels (p=0.05), and ESR was associated with a greater PD (p=0.044) and presence of red complex (p=0.030). Conclusion Different pharmacological treatments for RA affect the clinical condition and subgingival microbiota.

Medical practitioners record the condition status of a patient through qualitative and quantitative observations. The measurement of vital signs and molecular parameters in the clinics gives a complementary description of abnormal phenotypes associated with the progression of a disease. The Clinical Measurement Ontology (CMO) is used to standardize annotations of these measurable traits. However, researchers have no way to describe how these quantitative traits relate to phenotype concepts in a machine-readable manner. Using the WHO clinical case report form standard for the COVID-19 pandemic, we modeled quantitative traits and developed OWL axioms to formally relate clinical measurement terms with anatomical, biomolecular entities and phenotypes annotated with the Uber-anatomy ontology (Uberon), Chemical Entities of Biological Interest (ChEBI) and the Phenotype and Trait Ontology (PATO) biomedical ontologies. The formal description of these relations allows interoperability between clinical and biological descriptions, and facilitates automated reasoning for analysis of patterns over quantitative and qualitative biomedical observations.

Background Two RCTs found no survival benefit for completion lymphadenectomy after positive sentinel lymph node biopsy compared with observation with ultrasound in patients with melanoma. Recurrence patterns and regional control are not well described for patients undergoing observation alone. Methods All patients with a positive sentinel node biopsy who did not have immediate completion lymphadenectomy were identified from a single-institution database (1995–2018). First recurrences were classified as node only, local and in-transit (LCIT) only, LCIT and nodal, or systemic. Regional control and factors associated with recurrence survival were analysed. Results Median follow-up was 33 months. Of 370 patients, 158 (42·7 per cent) had a recurrence. The sites of first recurrence were node only (13·2 per cent), LCIT only (11·9 per cent), LCIT and nodal (3·5 per cent), and systemic (13·8 per cent). The 3-year postrecurrence melanoma-specific survival rate was 73 (95 per cent c.i. 54 to 86) per cent for patients with node-only first recurrence, and 51 (31 to 68) per cent for those with initial systemic recurrence. In multivariable analysis, ulceration in the primary lesion (hazard ratio (HR) 2·53, 95 per cent c.i. 1·27 to 5·04), disease-free interval 12 months or less (HR 2·38, 1·28 to 4·35), and systemic (HR 2·57, 1·16 to 5·65) or LCIT and nodal (HR 2·94, 1·11 to 7·79) first recurrence were associated significantly with decreased postrecurrence survival. Maintenance of regional control required therapeutic lymphadenectomy in 13·0 per cent of patients during follow-up. Conclusion Observation after a positive sentinel lymph node biopsy is associated with good regional control, permits assessment of the time to and pattern of recurrence, and spares lymphadenectomy-related morbidity in patients with melanoma.

Background and importance Despite the clinical benefits of therapy with control point inhibitors in several malignancies, this inhibition is closely linked to a series of immune related adverse events (irAEs). The early detection and management of these is of vital importance. Aim and objectives To identify and describe irAEs with programmed cell death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors in clinical practice. Material and methods A retrospective, descriptive, observational study was conducted in a 400 bed hospital in patients treated with immunotherapy (IT) from 1 January 2016 to 30 October 2018. Variables were age, gender, type of tumour, stage, IT, irAEs and grade, cycles until irAE appearance, irAE treatment and IT suspension. The electronic medical history was reviewed in OrionClinic and IT treatment in Farmis-Oncofarm. The causality of irAEs was ascertained on the basis of the European Society for Medical Oncology (ESMO) algorithms. Statistical analysis was performed with SPSS V.15. Results A total of 127 patients were treated with an average age of 65 years (range 36–88) and 75% were women: 76% of patients had non-microcytic lung cancer, 7% head–neck, 6% bladder, 5% breast, 4% renal, 2% melanoma and colorectal cancer. In 67% of patients, stage IV tumours were found, in 27% stage III, in 4% stage II and in 2% stage I. Nivolumab was prescribed in 54% of patients, pembrolizumab in 26%, atezolizumab in 13% and durvalumab in 7%. Fifty-two irAEs were identified. The average number of cycles until irAE appearance was 3.25 (range 1–57). The main irAEs were cutaneous (37%), gastrointestinal (23%), pneumonitis (14%) and endocrinological (8%); 64% grade I, 25% grade II, 12% grade III and no grade IV. Treatment was given for 66% of irAEs: oral corticoids (52%), topical corticoids (17%), antihistamines (12%) and hormone replacement therapy (5%). IT was resumed in 83% of patients. By the end of the study period, 31% of patients remained on therapy. Non-continuity was due to progression (55%), irAEs (10%) and other reasons (4%). Conclusion and relevance The most frequent irAEs in patients receiving IT were cutaneous and gastrointestinal, mostly transitory and grades I–II. They were mostly resolved with corticotherapy and antihistamines. Management of irAEs was presented on the basis of clinical experience; cooperation of patients, caregivers and healthcare professionals is required to watch over their safety to obtain the maximum efficacy with the lowest irAEs possible. References and/or acknowledgements No conflict of interest.

Structural equation models (SEM) are a type of multi-trait model increasingly being used for inferring functional relationships between multiple outcomes using operational data from livestock production systems. These data often present a hierarchical architecture given by clustering of observations at multiple levels including animals, cohorts and farms. A hierarchical data architecture introduces correlation patterns that, if ignored, can have detrimental effects on parameter estimation and inference. Here, we evaluate the inferential implications of accounting for, or conversely, misspecifying data architecture in the context of SEM. Motivated by beef cattle feedlot data, we designed simulation scenarios consisting of multiple responses in a clustered architecture. Competing fitted SEMs differed in their model specification so that data architecture was explicitly accounted for (M1; true model) or misspecified due to disregarding either the cluster-level correlation between responses (M2) or the correlation between observations of a response within a cluster (M3), or ignored all together (M4). Model fit was increasingly impaired when data architecture was misspecified or ignored. Both accuracy and precision of estimation were also negatively affected when data architecture was disregarded. Our findings are further illustrated using data from feedlot operations from the US Great Plains. Standing statistical recommendations that call for proper model specification capturing relevant hierarchical levels in data structure extend to the multivariate context of structural equation modeling. Supplementary materials accompanying this paper appear on-line.

The biotechnology industry is a relatively new a distinct field that involve using living organism to produce desired product. This industry includes firms that develop, manufacture, and market pharmaceutical products, agricultural products, environmental control product, e.t.c. based on advanced biotechnology research. Although the growth in the global biotechnology industry neared double digits the past two years, the threat of entry into the market is weak due to high barriers to entry. However, because of the ease and low-cost production using biotechnology, it has increased competition in some product. Leading European nations with strong biotech sectors such as the UK and Germany are investing heavily in regenerative medicine (RM), seeking competitive advantage in this emerging sector. However, in the broader biopharmaceutical sector the European Union (EU) is outperformed by the US on all metrics, reflecting longstanding problems: limited venture capital finance, a fragmented patent system, and relatively weak relations between academia and industry. The current global downturn has exacerbated these difficulties. The crisis comes at a time when the European Union is reframing its approach to the governance of innovation and renewing its commitment to the goal of making Europe the leading player in the global knowledge economy.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN Guidelines Panel meets at least annually to review comments from reviewers within the NCCN Member Institutions, examine relevant data, and reevaluate and update the recommendations. These NCCN Guidelines Insights summarize recent updates centered on treatment considerations for relapsed/refractory classic HL.

Introduction: Patients (pts) with hematological malignancies (HMs) are at increased risk for severe COVID19 infection and death (Grivas, 2021). Currently, vaccination represents the most effective prevention approach. HM pts have been shown to have lower immune responses to COVID19 vaccine, particularly those with lymphoid malignancies (LMs) (Herishanu, 2021; Thakkar 2021; Tzarfari 2021). We conducted an observational cohort study at Moffitt Cancer Center (MCC) to evaluate the immune response following one and two doses of the mRNA1273 (Moderna) vaccine in cancer pts. Here we report the results for pts with LMs and assessed associated factors. Methods: MCC pts who presented for the first mRNA-1273 vaccine dose from 1/12/2021-1/25/2021 and who provided consent were enrolled. Blood samples were collected prior to the 1 st and 2 nd doses (Days 1 and 29) and ~28 days after the 2 nd dose (Day 57). The IgG response against the SARS-CoV-2 spike (S) protein was measured using a two-step ELISA adapted from the Krammer (Icahn School of Medicine at Mount Sinai) protocol. The total 103 LM pts who received both vaccine doses and had samples at all time points were included in analyses. The 214 pts with solid tumors (ST) were included as comparison. Associations of seroconversion (SV) rates with pt characteristics were evaluated using the Fisher exact test or Chi-square test as appropriate. Associations of antibody (Ab) titers with pt characteristics were examined using Kruskal Wallis test. Factors independently associated with SV rates were evaluated using multivariable logistic regression. All analyses were performed using SAS 9.4 and R studio. Results: Baseline characteristics, cancer treatments and SV rates by these factors are listed in Tables 1 and 2. 55 pts had B-cell non-Hodgkin lymphoma (B-NHL), 23 had chronic lymphocytic leukemia (CLL), 15 had T- or NK-cell lymphoma (T/NK lymphoma) and 10 had Hodgkin lymphoma (HL). SV rates were significantly lower for LM pts compared to ST pts (49.5% vs 86.9% after the 1st dose and 68.9% vs 98.1% after the 2 nd dose, respectively, p12 months ago and 6 pts were in remission and have not received any cancer treatment after CAR-T. Pts with CLL and B-NHL but not on CD20 mAb/BTKi/PI3Ki/venetoclax or post CAR-T had much higher SV rates (31.3-60.5% after dose 1 and 79.0-81.3% after dose 2, Table 3). Other factors associated with lack of SV after 2 doses included: lymphocyte In the univariate model, Ab titers after 1 and 2 doses were significantly lower in pts with diagnosis of CLL/B-NHL, low lymphocyte count, low IgG and on cancer treatment (Figures 1-3). HL and T/NK lymphoma had titers comparable to solid tumors (Figure 1). Conclusions: Pts with CLL and B-NHL had low SV rates and Ab titers after receiving the mRNA-1273 vaccine when compared with ST, HL and T/NK-lymphoma. Current or past treatments with CD20 mAb/BTKi/PI3Ki/venetoclax and CAR-T were associated with lower immune response, with pooled SV rates of 16.7% after 2 doses. In general, LM pts had lower SV rates and Ab titers after the 1 st dose vs ST, but responses improved after the 2 nd dose. Further studies are needed to improve immune responses to COVID19 vaccines in LM pts, including the potential role of a 3 rd booster dose. Figure 1 Figure 1. Disclosures Gaballa: Adaptive Biotechnologies: Research Funding; Epizyme: Consultancy, Research Funding; TG therapeutics: Consultancy, Speakers Bureau; Beigene: Consultancy; ADC Therapeutics: Consultancy. Saeed: Bristol-Myers Squibb Company: Consultancy; sano-aventis U.S.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceutica Products, LP: Consultancy, Other: investigator; Celgene Corporation: Consultancy, Other: investigator; MEI Pharma Inc: Consultancy, Other: investigator; Kite Pharma: Consultancy, Other: investigator; Other-TG therapeutics: Consultancy, Other: investigator; Nektar Therapeutics: Consultancy, Other: research investigator; MorphoSys AG: Consultancy, Membership on an entity's Board of Directors or advisory committees; Other-Epizyme, Inc.: Consultancy; Other-Secura Bio, Inc.: Consultancy; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees. Shah: Pharmacyclics/Janssen: Honoraria, Other: Expenses; Pfizer: Consultancy, Other: Expenses; BeiGene: Consultancy, Honoraria; Servier Genetics: Other; Jazz Pharmaceuticals: Research Funding; Precision Biosciences: Consultancy; Amgen: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Acrotech/Spectrum: Honoraria; Novartis: Consultancy, Other: Expenses; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy; Incyte: Research Funding. Locke: Janssen: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; EcoR1: Consultancy; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding; Calibr: Consultancy, Other: Scientific Advisory Role; Amgen: Consultancy, Other: Scientific Advisory Role; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; Umoja: Consultancy, Other; Cowen: Consultancy; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Emerging Therapy Solutions: Consultancy; Gerson Lehrman Group: Consultancy; Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Wugen: Consultancy, Other; Takeda: Consultancy, Other; Novartis: Consultancy, Other, Research Funding; Legend Biotech: Consultancy, Other. Chavez: Abbvie: Consultancy; AstraZeneca: Research Funding; Kite/Gilead: Consultancy; Karyopharm Therapeutics: Consultancy; MorphoSys: Speakers Bureau; Epizyme: Speakers Bureau; Bristol Myers Squibb: Speakers Bureau; Merck: Research Funding; Adaptive: Research Funding; BeiGene: Speakers Bureau; Novartis: Consultancy; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lancet: AbbVie: Consultancy; ElevateBio Management: Consultancy; Daiichi Sankyo: Consultancy; Celgene/BMS: Consultancy; Millenium Pharma/Takeda: Consultancy; BerGenBio: Consultancy; Agios: Consultancy; Astellas: Consultancy; Jazz: Consultancy. Sokol: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Pinilla Ibarz: AbbVie, Janssen, AstraZeneca, Novartis, TG Therapeutics, Takeda: Consultancy, Other: Advisory; Sellas: Other: ), patents/royalties/other intellectual property; MEI, Sunesis: Research Funding; AbbVie, Janssen, AstraZeneca, Takeda: Speakers Bureau. Giuliano: Merck & CO: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Cattle are a reservoir for Escherichia coli O157 and they shed the pathogen in their feces. Fecal contaminants on the hides can be transferred onto carcasses during processing at slaughter plants, thereby serving as a source of foodborne infection in humans. The detection of E. coli O157 in cattle feces is based on culture, immunological, and molecular methods We evaluated the diagnostic sensitivity and specificity of one culture- and two PCR-based tests for the detection of E. coli O157 in cattle feces, and its true prevalence using a Bayesian implementation of latent class models. A total of 576 fecal samples were collected from the floor of pens of finishing feedlot cattle in the central United States during summer 2013. Samples were enriched and subjected to detection of E. coli O157 by culture (immunomagnetic separation, plating on a selective medium, latex agglutination, and indole testing), conventional PCR (cPCR), and multiplex quantitative PCR (mqPCR). The statistical models assumed conditional dependence of the PCR tests and high specificity for culture (mode=99%; 5th percentile=97%). Prior estimates of test parameters were elicited from three experts. Estimated posterior sensitivity (posterior median and 95% highest posterior density intervals) of culture, cPCR, and mqPCR was 49.1% (44.8-53.4%), 59.7% (55.3-63.9%), and 97.3% (95.1-99.0%), respectively. Estimated posterior specificity of culture, cPCR, and mqPCR were 98.7% (96.8-99.8%), 94.1% (87.4-99.1%), and 94.8% (84.1-99.9%), respectively. True prevalence was estimated at 91.3% (88.1-94.2%). There was evidence of a weak conditional dependence between cPCR and mqPCR amongst test positive samples, but no evidence of conditional dependence amongst test negative samples. Sensitivity analyses showed that overall our posterior inference was rather robust to the choice of priors, except for inference on specificity of mqPCR, which was estimated with considerable uncertainty. Our study evaluates performance of three diagnostic tests for detection of E. coli O157 in feces of feedlot cattle which is important for quantifying true fecal prevalence and adjusting for test error in risk modeling.

Introduction: Vyxeos® is a liposomal formulation employing a 1:5 molar ratio of daunorubicin:cytarabine. Clinical trials in high risk acute myeloid leukemias demonstrated a significant benefit in CR rates and median OS, culminating in FDA approval August 2017. Emerging pediatric data suggest this benefit may extend to acute lymphoblastic leukemia (ALL). The following pilot trial was performed to better understand the activity and toxicity profile in adults with relapsed and refractory ALL. Methods: Adults with ALL or mixed phenotype leukemia were eligible if >5% lymphoblasts and/or extramedullary disease >1x1cm. Induction consisted of Vyxeos 100 units/m2 on days 1, 3 and 5. Those with clinical benefit could receive up to 3 cycles of consolidation delivered at 65 units/m2 on days 1 & 3 after recovery of neutrophils (>500 cells/uL) and platelets (>50,000 cells/uL). Response: 11 patients (pts) have been treated to date, with median age of 39y (22-74y), 9 male, and 3 Caucasian. Six pts had B-ALL, including 1 B-myeloid. Four of 5 T-ALL pts had early T-cell precursor (ETP) phenotype. NGS was available in 9 pts, and included TP53 mutation (n=4), and PH-like changes (n=2). Median prior lines of therapy was 3, with 7 pts showing primary refractory disease. Prior blinatumomab, inotuzumab, CAR-T cell therapy, and allogeneic transplant were noted in 5, 2, 1, and 3 pts. Pancytopenia was uniform during induction, with febrile neutropenia noted in 9 pts. One pt passed from pneumonia after moving to comfort measures in lieu of intubation 20 days after Vyxeos, and is non-evaluable for response. A second pt developed grade 3 sepsis. The remainder of infections were grade 1-2. One pt had grade 3 gastrointestinal bleed, and 3 pts had grade 1 spontaneous subdural bleeding. One pt developed recurrent pericarditis in setting of anterior mediastinal mass. One case of veno-occlusive disease was observed in a pt with prior allogeneic transplant and inotuzumab. Median time to ANC recovery was 33.5 days among 10 evaluable pts. Two pts with refractory disease failed to recover platelets; among the remaining pts, median time to platelet recovery was 30.5 days. Adverse events were uncommon during consolidation, and include foot cellulitis and myopericarditis, each in 1 pt. Among 10 evaluable pts, 3 achieved CR/CRi, including 2 ETP T-ALL and one B-ALL. Two pts with TP53 mutation demonstrated >50% blast reduction with hematologic recovery, allowing for prolonged time to subsequent therapy. Four pts received 1-3 cycles consolidation. One pt was bridged to donor leukocyte infusion. Responses were noted in only 2 pts after progression following Vyxeos, highlighting refractory status of those enrolled. Median PFS was 57 days (95%CI: 10, 105), time to next therapy 76 days (95%CI: 47, 105), and OS 223 days (95%CI: 144, 302). Conclusions Vyxeos in high-risk refractory adult ALL was overall well tolerated and active, with median OS of approximately 7.5 months in this pilot trial. Confirmation of benefit in a larger study is warranted, incorporating a second induction course and/or the addition of novel agents to further improve on remission rate and duration of response. Disclosures Shah: Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Servier Genetics: Other; BeiGene: Consultancy, Honoraria; Acrotech/Spectrum: Honoraria; Pharmacyclics/Janssen: Honoraria, Other: Expenses; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Precision Biosciences: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Other: Expenses; Pfizer: Consultancy, Other: Expenses; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy. Chavez: Astra Zeneca: Research Funding; Novartis: Consultancy; Merck: Research Funding; Morphosys: Speakers Bureau; Adaptive Biotech: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Beigene: Speakers Bureau; Kite/Gilead: Consultancy; karyopharm: Consultancy; Epizyme: Speakers Bureau; Abbvie: Consultancy. Sokol: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Lancet: Celgene/BMS: Consultancy; Millenium Pharma/Takeda: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy; BerGenBio: Consultancy; ElevateBio Management: Consultancy; Agios: Consultancy; Astellas: Consultancy; Jazz: Consultancy. OffLabel Disclosure: Vyxeos is being evaluated in the described trial for the treatment of relapsed or refractory acute lymphoblastic leukemia in adults.

The COVID-19 pandemic has hugely impacted global public health and economy. The COVID-19 has also shown potential impacts on maternal perinatal and neonatal outcomes. This systematic review aimed to summarize the evidence from existing systematic reviews about the effects of SARS-CoV-2 infections on maternal perinatal and neonatal outcomes. We searched PubMed, MEDLINE, Embase, and Web of Science in accordance with PRISMA guidelines, from 1 December 2019 to 7 July 2021, for published review studies that included case reports, primary studies, clinical practice guidelines, overviews, case-control studies, and observational studies. Systematic reviews that reported the plausibility of mother-to-child transmission of COVID-19 (also known as vertical transmission), maternal perinatal and neonatal outcomes, and review studies that addressed the effect of SARS-CoV-2 infection during pregnancy were also included. We identified 947 citations, of which 69 studies were included for further analysis. Most (>70%) of the mother-to-child infection was likely due to environmental exposure, although a significant proportion (about 20%) was attributable to potential vertical transmission of SARS-CoV-2. Further results of the review indicated that the mode of delivery of pregnant women infected with SARS-CoV-2 could not increase or decrease the risk of infection for the newborns (outcomes), thereby emphasizing the significance of breastfeeding. The issue of maternal perinatal and neonatal outcomes with SARS-CoV-2 infection continues to worsen during the ongoing COVID-19 pandemic, increasing maternal and neonatal mortality, stillbirth, ruptured ectopic pregnancies, and maternal depression. Based on this study, we observed increasing rates of cesarean delivery from mothers with SARS-CoV-2 infection. We also found that SARS-CoV-2 could be potentially transmitted vertically during the gestation period. However, more data are needed to further investigate and follow-up, especially with reports of newborns infected with SARS-CoV-2, in order to examine a possible long-term adverse effect.

Context/Objective Marginal zone lymphoma (MZL) is an indolent non-Hodgkin lymphoma (NHL) accounting for 8–12% of NHL. Extra-nodal MZL (EMZL) is the most common subgroup, comprising ~70% of cases. Bendamustine and rituximab (BR) are commonly used as frontline therapy based on trials involving other indolent NHL, mainly follicular NHL. No trials have prospectively assessed frontline BR specifically in EMZL. We retrospectively report outcomes among EMZL patients receiving frontline BR. Design All patients with EMZL receiving frontline BR between 2011–2021 were identified in tumor registry. Treatment responses were assessed per 2007 Cheson criteria. Statistical analysis was performed using SPSS. Results Twenty-five patients met inclusion criteria. Median age was 69 years (40–81). Patients were White (80.0%), Asian (4.0%), or Other (16.0%). Five patients (20.0%) were stage I/II, and 19 (76.0%) were stage III/IV. MALT-IPI was low, intermediate, and high risk in 2 (10.5%), 9 (37.5%), and 8 (42.1%) patients, respectively. ECOG was Conclusion BR is safe/effective as frontline therapy for patients with EMZL. Responses were similar to previous reports of frontline BR in other indolent lymphomas.

This portion of the NCCN Guidelines for Hodgkin lymphoma (HL) focuses on the management of classical HL. Current management of classical HL involves initial treatment with chemotherapy or combined modality therapy followed by restaging with PET/CT to assess treatment response using the Deauville criteria (5-point scale). The introduction of less toxic and more effective regimens has significantly advanced HL cure rates. However, long-term follow-up after completion of treatment is essential to determine potential long-term effects.

Background: The aim of this study was to evaluate the outcomes of priming salvage radioimmunotherapy (RIT) with a low dose of external beam radiotherapy (EBRT) in patients with relapsed low grade non-Hodgkin lymphoma (LG-NHL). Methods: Patients who received salvage RIT with or without 2 × 2 Gy EBRT between March 2009 and February 2013 were retrospectively reviewed at a single institution. Planning target volume (PTV) for EBRT was created by adding a 1–2 cm expansion to the gross tumor volume depending on the anatomical location. Kaplan−Meier method via log-rank was employed to analyze the endpoints freedom from progression (FFP) and overall survival (OS). Results: We identified 22 patients who received salvage RIT without chemotherapy with a median follow up of 34 months. Of these, 9 (41%) patients were treated with EBRT immediately prior to RIT, and 13 (59%) received salvage RIT alone. Median FFP was not reached in patients who underwent combination treatment, while it was 9 months for patients treated with RIT alone ( p = 0.02). OS for all patients at 36 months was 80.3% with no significant difference between the two groups ( p = 0.88). On univariate analysis, the addition of EBRT was associated with improved FFP [hazard ratio (HR) = 4.17; 95% confidence interval (CI), 1.24–19.1; p = 0.02)]. No long term toxicities were reported in both groups. Conclusions: RIT outcomes and effects were improved with addition of low-dose EBRT immediately prior to it, in the treatment of relapsed LG-NHL with no additional toxicity. This study is hypothesis-generating and the findings should be validated in prospective studies.

ELISA-Based detection of HBV infection in correctional facilities in Sokoto metropolis, Sokoto state Nigeria was carried out using a questionnaire survey to determine the associated risk factors of the disease and serological method using [Enzyme link immunosorbent Assay (ELISA)] to determine hepatitis B surface antigen (HBSAg) among inmates. Of the 180 participants from the two correctional facilities in Sokoto state (Sokoto central prison and Remand home) overall prevalence rate of (42.2%) was obtained. The distribution of HBV infection according to age was statistically significant, and the age groups of 21-25 and 36-40 years had the highest prevalence rates (61.3%). However higher prevalence was recorded among males (42.6%) than females (36.4%). Analysis of spatial distribution of prevalence of HBV infection showed that Remand home (juvenile detention centre) had the highest prevalence rate of (75%). It was concluded that hepatitis B virus infection was found to be prevalent in correctional facilities in Sokoto state in which duration of stay and multiple sexual partners were the main risk factors. Furthermore there is need for Nigerian government to establish a policy that would make general screening of all the inmates in correctional facilities for HBV infection and vaccinate them against the disease.