A Novel IoT-Enabled Healthcare Monitoring Framework and Improved Grey Wolf Optimization Algorithm-Based Deep Convolution Neural Network Model for Early Diagnosis of Lung Cancer.

Lung cancer is a high-risk disease that causes mortality worldwide; nevertheless, lung nodules are the main manifestation that can help to diagnose lung cancer at an early stage, lowering the workload of radiologists and boosting the rate of diagnosis. Artificial intelligence-based neural networks are promising technologies for automatically detecting lung nodules employing patient monitoring data acquired from sensor technology through an Internet-of-Things (IoT)-based patient monitoring system. However, the standard neural networks rely on manually acquired features, which reduces the effectiveness of detection. In this paper, we provide a novel IoT-enabled healthcare monitoring platform and an improved grey-wolf optimization (IGWO)-based deep convulution neural network (DCNN) model for lung cancer detection. The Tasmanian Devil Optimization (TDO) algorithm is utilized to select the most pertinent features for diagnosing lung nodules, and the convergence rate of the standard grey wolf optimization (GWO) algorithm is modified, resulting in an improved GWO algorithm. Consequently, an IGWO-based DCNN is trained on the optimal features obtained from the IoT platform, and the findings are saved in the cloud for the doctor's judgment. The model is built on an Android platform with DCNN-enabled Python libraries, and the findings are evaluated against cutting-edge lung cancer detection models.

A Clinical Score For Predicting Complications Following Breast Reduction.

Objectives: To establish a clinical score for morbidity prediction based on patient-related risk factors after breast reduction surgery. Method: The retrospective study was conducted at the Department of Plastic and Reconstructive Surgery, Kafrelsheikh University Hospital, Egypt, and comprised data of female patients with bilateral macromastia who underwent breast reduction, using the inferior pedicle invertedT technique between February 2019 and June 2020. After data retrieval, risk factors and complications were documented and related to the patients'risk factors Data was analysed using SPSS 20. RESULTS: Of the 30 cases, 20(66.7%) were aged ≥35 years, 16(53.3%) had body massindex ≥37kg/m2 and 27(90%) were non-smokers. The mean preoperative haemoglobin level was 12.15±1.115g/dL and the mean weight of tissue resected on both sides was 2074.17±696.12gm. Factors significantly associated with complications included smoking, suprasternal notch to nipple distance ≥38cm, haemoglobin <12.5g/dL, the weight of excised tissue ≥2000gm and a positive family history of macromastia. The total score of the morbidity prediction scale ranged 2-190, with the best cut-off value being ≥93. The scale had 100% sensitivity,specificity, positive predictive value, negative predictive value and 100 percent accuracy. CONCLUSIONS: Ability to predict postoperative surgical-site morbidity may optimise safety as well as outcome after reduction mammaplasty.

Outcomes Of Mesh Fixation Versus Non Fixation In Laparoscopic Transabdominal Preperitoneal Inguinal Hernia Repair: A Randomized Clinical Study.

Objectives: The present study aimed to compare the results of laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair with and without mesh fixation regarding postoperative pain, recurrence, operative time, and complications. METHODS: This randomized controlled clinical trial included 100 patients who underwent TAPP inguinal hernia with mesh fixation (group A) or a fixation-free procedure (group B) for early onset inguinal hernia at the General Surgery Department, Kafrelsheikh University Hospital, from January 2021 to June 2022. RESULTS: The parameters for pain assessment (NRS) in the first week (mean 7 (5 - 8)), the first month (mean 3 (1 - 5)), and after three months(mean 0 - (70% of patients), (mean 1- (30% of patients) were significantly higher in the fixation group (p<0.001). The fixation group had significantly more operative time than non fixation, with a mean (69.34±13.55, 60.92±10.18) respectively. Recurrence rate and postoperative complications did not show any significant difference between the studied groups. CONCLUSIONS: Mesh non-fixation for laparoscopic TAPP hernia repair is safe, practical, and effective with minimal postoperative pain and no increased risk of recurrence.

Safe Stapleless Laparoscopic Splenectomy; Use Of Hem-O-Lok To Control The Splenic Hilum.

Objectives: To evaluate Hem-o-Lok polymer clips' feasibility, safety and cost-effectiveness in controlling the splenic pedicle during paediatric laparoscopic splenectomy. Method: The prospective study was conducted from May 2019 to December 2021 at Kafrelsheikh University Hospital, Egypt, and comprised children of either gender aged <18 years who had benign haematological diseases and were indicated for laparoscopic splenectomy. During the procedure, Hem-o-Lok clips were used for controlling the splenic pedicle. Patients were encouraged to ambulate the same day, and the drain was removed 24hours postoperatively. The cases were followed up for three months postoperatively. RESULTS: Of the 23 subjects, 11(47.8%) were boys and 12(52.2%) were girls. The overall mean age was 8.74±3.44 years (range: 4-15 years). There were 6(26%) cases of spherocytosis, 1(4.3%) immune thrombocytopenic purpura and 16(69.6%) with thalassemia major. The mean operative time was 93.43±29.87 minutes(range: 65-180 minutes). There was no conversion to open splenectomy and no mortality. There were 2(8.7%) cases of minor and 1(4.3%) of major intraoperative bleeding. All the 3(100%) cases were controlled laparoscopically. No postoperative bleeding occurred and no cases required postoperative blood transfusion. CONCLUSIONS: Controlling both the splenic artery and vein using Hem-o-Lok clips was found to be feasible, safe and cost-effective.

Expanding Scope About Factors Influencing Seroma Formation After Breast Cancer Surgery.

Objectives: To determine the incidence of seroma formation after breast cancer surgery, and its association with common risk factors. Method: The correlationalstudy was conducted at the General Surgery department of Kafrelsheikh University Hospital, Egypt, from March 2020 to March 2022 and comprised patients having breast cancerstage I, II or III, as per the Tumour Node-Metastasis classification, who were scheduled to undergo modified radical mastectomy, breast conserving surgery or reconstructive surgery. Baseline, intraoperative and postoperative data was collected on a proforma. Data was analysed using SPSS 22. RESULTS: Of the 50 female patients with mean age 45±5.20 (range: 20-70 years), 30(60%) were in the elderly group aged >45 years, while 20(40%) were aged <45years. Overall, 12(24%) cases developed seroma; 9(30%) in the elderly group. There were 24(48%) cases of modified radical mastectomy, and 8(33.3%) had seroma. Electrocautery was used for breast dissection in 30(60%) cases, and, among them, seroma developed in 10(33.3%) patients. CONCLUSIONS: Age, body weight, afflicted breast side, site, and size of breast mass were not found to be significant predictors of seroma formation following breast cancer surgery.

Oncoplastic Volume Displacement Surgical Techniques For Early Primary Breast Cancer: A Case Series.

Oncoplastic breast surgery (OPS) is a new strategy for expanding breast-conserving surgical options, lowering mastectomies rates, and preventing deformities. OPS is based on the use of plastic surgical reconstruction after breast cancer removal. The study aims to assess volume displacement oncoplastic procedures for early primary breast cancer in terms of recurrence and cosmoses. A case series study was done on 20 patients with early breast cancer who underwent oncoplastic volume displacement techniques in the period from March 2019 to March 2021 in Kafrelsheikh University Hospital, Egypt. OPS techniques included were Racquet, Benelli, Batwing and Grisotti technique. The study concluded that OPS are oncologically safe (100%) with no recurrence and a better aesthetic outcome (90%).

Relation Between Baseline CXCR1 Expression And Neoadjuvant Chemotherapy Response In Breast Cancer Patients.

Objectives: To examine the C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues prior to neo-adjuvant chemotherapy, and its relationship to neo-adjuvant chemotherapy effectiveness and other prognostic variables. Method: The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2018 to March 2021, and comprised patients with recent histopathologically proven breast cancer cases eligible for chemotherapy. Paraffin blocks of tumourspecimens were stained by immunohistochemicalstain using concentrating rabbit anti-human C-X-C Motif Chemokine Receptor 1 polyclonal antibody kits. C-X-C Motif Chemokine Receptor 1 expression was classified into low and high categories. Patients were followed for 2 years for treatment response, disease recurrence and mortality. Data was analysed using SPSS 25. RESULTS: Of the 100 females with mean age 50.2±12.1 years, 52(52%) had their left side affected, while 48(48%) had their rightside affected. There were 52(52%) cases with mean age 49.2±12.9 years having high C-X-C Motif Chemokine Receptor 1 expresssion, while 48(48%) with mean age 51.4±11.2 years had low expression. There was a significant association between high expression and advanced tumour grade, advanced tumourstage, higher frequency of triple negative breast cancer and higher frequency of Ki-67-positive cancers (p<0.05). Patients with high C-X-C Motif Chemokine Receptor 1 expression had significantly lower frequency of complete pathological response when compared with patients with low expression (p<0.001). Patients with high expression had higher frequency of recurrence, shorter disease-free survival, higher mortality and shorter overall survival, but the difference was not significant (p>0.05). Multivariate logistic regression analysis identified triple negative hormonal status (p=0.031) and high baseline C-X-C Motif Chemokine Receptor 1 expression (p<0.001) as significant predictors of complete pathological response. CONCLUSIONS: There was found to be a link between baseline C-X-C Motif Chemokine Receptor 1 expression in breast cancer tissues and pathological response to neoadjuvant therapy in breast cancer patients.

Needlescopic Primary Paediatric Inguinal Hernia Repair By Hernia Sac Disconnection And Peritoneal Closure.

Objectives: To evaluate the short-term outcome of the needlescopic hernia sac disconnection and peritoneal closure in the treatment of primary paediatric inguinal hernia. Method: The prospective study was conducted from April 2019 to April 2021 at the Paediatric Surgery Unit of the General Surgery Department at Kafrelsheikh University Hospital, Egypt, and comprised patients aged 6-144 months having uncomplicated paediatric inguinal hernia. The patients were subjected to needlescopic hernia sac disconnection and peritoneal closure. The follow-up protocol included outpatient visits at 1 week and at 1, 3 and 6 months postoperatively to check for recurrence and other complications. Data was analysed using SPSS 24. RESULTS: Of the 50 patients with 65 hernias, 37(74%) were males and 13(26%) were females. The overall mean age was 50.78± 31.74 months (range: 9-120 months) and mean internal ring diameter was 11.90±3.518mm (range: 8-20mm). The mean operative time was 20.66±2.94 minutesfor unilateral cases and 30.60±5.15 minutesfor bilateral cases. There was no conversion to conventional laparoscopy or to open herniotomy. All cases were followed up for a mean of 11.56± 3.99 months. No recurrence was encountered in any case and the scars were invisible in 40(80%) cases 6 months postoperatively. CONCLUSIONS: Needlescopic hernia sac disconnection and peritoneal closure wasfound to be feasible,safe and effective in the treatment of primary paediatric inguinal hernia.

Effect Of Laparoscopic Sleeve Gastrectomy On Vitamin D, Parathormone Hormone, And Serum Calcium Levels.

Objectives: To evaluate the effect of laparoscopic sleeve gastrectomy on vitamin D status, parathyroid hormone,serum calcium and the effectiveness of vitamin D supplementation. Method: The prospective study was conducted at the General Surgery Department of Kafrelsheikh University Hospital, Egypt, in November 2019, and comprised morbidly obese patients of either gender who were managed with laparoscopic sleeve gastrectomy. Serum levels of vitamin D, calcium and parathyroid hormone were assessed at baseline and at 6 and 12 months after the surgery. All subjects were given 400 IU/day of vitamin D. If the level of vitamin D was <30ng/ml, further doses of calcifediol 200,000 IU were added every two weeks. Data was analysed using SPSS 22. RESULTS: Of the 40 patients, 28(70%) were females and 12(30%) were males. The overall mean age was 33.9±10.8, mean weight was 136±18.29kg and mean body massindex was 50±4.9kg/m2 . The mean operative time was 64.5±13.6 minutes, and the mean hospitalstay was 1.8±1.1 days. There wassignificant reduction in body massindex values after the surgery (p<0.05). Vitamin D level was 19.2±3.2 ng/ml at baseline, which rose to 21.4±2.7 ng/ml at 6 months and 26.6±2.8 ng/ml at 12 months post-surgery (p<0.05). Preoperative parathyroid hormone level was 58.3±7.8 pg/ml , which went down to 48.6±7.4 pg/ml at 6 months, and 41.3±6.5 pg/ml at 12 months postoperatively (p<0.05). The mean serum calcium level at baseline was 9±0.4mg/dL, which rose to 9.2 ±0.3mg/dL and 9.5±0.4 mg/dL at 6 and 12 months post-surgery (p<0.05). CONCLUSIONS: Low vitamin D complications could be decreased postoperatively by administering vitamin D as a routine treatment. Postoperative monitoring of vitamin D, parathyroid hormone and serum calcium levels is essential.

Clinical Significance Of Baseline And Post-Treatment CXCR1 Expression In Women With Breast Cancer Having Received Neoadjuvant Chemo Therapy.

Objectives: To examine the chemokine receptor type 1 expression in breast cancer tissues before and after neoadjuvant chemotherapy, and its relationship with pathological response to neoadjuvant chemotherapy and other clinical variables. Method: The prospective study was conducted at Kafrelsheikh University Hospital, Egypt, from November 2018 to March 2021, and comprised female patients with new histopathologically proven breast cancer eligible for chemotherapy. Paraffin blocks of tumourspecimens were stained immunohistochemically using concentrated rabbit anti-human chemokine receptor type 1 polyclonal antibody kits. The patients were followed up for treatment response, disease recurrence and mortality. Data was analysed using SPSS 25. RESULTS: Of the 100 patients with mean age 50.2±12.1 years, 40(40%) in group A with mean age 55.1±9.3 showed marked response and 60(60%) in group B with mean age 47.0±12.7 yearsshowed mild/moderate response (p<0.001). Group A patients had significantly lower baseline and post-treatment chemokine receptor type 1 expression compared to group B patients (p<0.05). The change in chemokine receptor type 1 expression was not significantly different (p>0.05). Patients with tumour grade 3 had significantly higher baseline chemokine receptor type 1 expression compared to patients with tumour grade 2. Tumourstage and post-treatment chemokine receptor type 1 expression were also significantly interlinked (p<0.05). Multivariate regression analysisidentified patients'age, baseline chemokine receptor type 1 and post-treatment chemokine receptor type 1 expressions as predictors of treatment response. CONCLUSIONS: There was found to be an association between baseline and post-treatment chemokine receptor type 1 expression in breast cancer tissues and pathological response to neoadjuvant chemo therapy in such patients.

Physician Awareness of Immune-Related Adverse Events of Immune Checkpoint Inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have been proven to be very effective in the treatment of multiple cancers. They have a unique side-effect profile distinct from conventional chemotherapy that can manifest as immune-related adverse events (irAEs). With expanding ICI use, clinicians will increasingly encounter irAEs, and thus adequate physician knowledge on their recognition and management is crucial. METHODS: To assess physician knowledge of irAEs due to ICIs, an online survey was administered to resident physicians in internal medicine (IM), emergency medicine, and family medicine (FM), as well as to faculty physicians in IM and FM. RESULTS: We sent the survey to 413 physicians and received responses from 155 (38%), of which 110 were residents and 45 were faculty. Pembrolizumab was identified as an ICI by 79% of physicians, nivolumab by 64%, and ipilimumab by 55%. Twenty-five percent incorrectly thought infliximab and adalimumab were ICIs. Most physicians (93%) were able to identify the gastrointestinal tract as an irAE site, whereas only 57% and 67% were able to identify cardiovascular and renal systems as irAE sites, respectively. A total of 59% believed steroids negatively affect efficacy of ICIs and should be used with caution to treat irAEs, 65% incorrectly thought endocrinopathies due to irAEs are usually reversible, and 45% of FM residents considered antibiotics as the mainstay of treatment in ICI-mediated colitis. On a self-rated scale from 0 to 100, the median comfort level for all physicians in recognizing irAEs was 15 and for treatment of irAEs was 10. CONCLUSIONS: Significant knowledge gaps exist among residents and faculty physicians across multiple specialties regarding the recognition and treatment of irAEs due to ICIs. Given that these physicians are usually the first point of contact with patients, physician education on identification and treatment of irAEs is needed. Early detection of these toxicities is critical for their resolution.

Multi-step Synthesis, Characterization and Photophysical Investigation of Novel Biologically Active Heterocyclic Chalcone (AECO).

Novel alkylated heterocyclic chalcone (E)-1-(2-(allyloxy)phenyl)-3-(9-ethyl-9H-carbazol-3-yl)prop-2-en-1-one (AECO) with extended π-bond was prepared by the multi-steps synthesis. The structure of the AECO was established by the spectroscopic technics and purity of the compound was confirmed by the elemental analysis. Physicochemical parameters of the AECO such as molar absorption coefficient, transition dipole moments, stokes shift, oscillator strength and fluorescence quantum yield were calculated in ten various solvents on the basis of polarity of the solvents to see the effect of the solvent with AECO. Interaction of the AECO chromophore with cationic CTAB and anionic SDS surfactants were determined by using the fluorescence spectroscopy techniques. The intensity of the florescence spectrum increase with increasing the concentrations of surfactants. This suggests that strong interaction occurs between AECO with surfactants and this interaction arise from electrostatic forces. So, AECO chromophore could be used as analysis to define the Critical Micelle Concentration (CMC) of the surfactants. In addition the in-vitro antibacterial active of novel heterocyclic chalcone agents four bacteria's strain were evaluated and result showed AECO is beater antibacterial agent against Gram-Negative Bacteria (E. coli and S. flexneri) as compare to the Gram Negative Bacteria with respected to the standard drug Tetracycline.

Hierarchical Tubular Architecture Constructed by Vertically Aligned CoS2 -MoS2 Nanosheets for Hydrogen Evolution Electrocatalysis.

Developing efficient electrocatalysts for the hydrogen evolution reaction (HER) is crucial for establishing a sustainable and environmentally friendly energy system, but it is still a challenging issue. Herein, hierarchical tubular-structured CoS2 -MoS2 /C as efficient electrocatalysts are fabricated through a unique metal-organic framework (MOF) mediated self-sacrificial templating. Core-shell structured MoO3 @ZIF-67 nanorods are used both as a precursor and a sacrificial template to form the one-dimensional tubular heterostructure where vertically aligned two-dimensional CoS2 -MoS2 nanosheets are formed on the MOF-derived carbon tube. Trace amounts of noble metals (Pd, Rh, and Ru) are successfully introduced to enhance the electrocatalytic property of the CoS2 -MoS2 /C nanocomposites. The as-synthesized hierarchical tubular heterostructures exhibit excellent HER catalytic performance owing to the merits of the hierarchical hollow architecture with abundantly exposed edges and the uniformly dispersed active sites. Impressively, the optimal Pd-CoS2 -MoS2 /C-600 catalyst delivers a current density of 10 mA cm-2 at a low overpotential of 144 mV and a small Tafel slope of 59.9 mV/dec in 0.5 m H2 SO4 . Overall, this MOF-mediated strategy can be extended to the rational design and synthesis of other hollow heterogeneous catalysts for scalable hydrogen generation.

Synthesis, photophysical properties, and density functional theory studies of phenothiazine festooned vinylcyclohexenyl-malononitrile.

A novel phenothiazine derivative conjugated with vinylcyclohexenyl-malononitrile (PTZ-CDN) was synthesized through the Knoevenagel reaction of 10-octyl-10H-phenothiazine-3,7-dicarbaldehyde with 2-(3,5,5-trimethylcyclohex-2-en-1-ylidene)-malononitrile and fully characterized. The UV-vis absorption spectra of PTZ-CDN in different solvents showed a λmax band at 497-531 nm with a high molar extinction coefficient attributed to intramolecular charge transfer (ICT) with the characteristics of a π-π* transition. Increasing the solvent polarity resulted in a bathochromic shift of λmax . The PTZ-CDN fluorescence emission spectra were more sensitive to increasing the solvent polarity than the absorption spectra; they displayed a blue shift of λem by 85 nm. To understand the behaviour of the PTZ-CDN derivative, Stokes' shift ( Δ ν ¯ ) with respect to the solvent polarity, Lippert-Mataga and linear solvation-energy relationship (LSER) models were applied in which the LSER showed better regression than the Lippert-Mataga plots (r2 = 0.9627). Finally, the TD-density functional theory (DFT) electronic transition spectra in dioxane and dimethyl formamide (DMF) were calculated. The DFT data showed that λmax resulted from the support of the highest occupied molecular orbital to the lowest unoccupied molecular orbital transition with 74% and 99% in dioxane and DMF, respectively.

Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene.

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13 × 10(-14) for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32-1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94-1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47-9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions.

Pharmacology and therapeutics resource session attendance and academic performance of pre-clerkship medical students in problem-based learning curricula.

BACKGROUND: The relationship between large-group classroom attendance by students and test achievement in problem-based learning (PBL) curricula is unclear. This study examined the correlation between attendance at resource sessions (hybrid lectures in the PBL curriculum) and test scores achieved in pharmacology and determined whether the score achieved was related to student gender. METHODS: A cross-sectional observational study over one academic year of 1404 pre-clerkship medical students was performed. Class attendance during pharmacology resource sessions and MCQ test scores achieved in pharmacology were analysed. RESULTS: The percentage of students' attendance in resource sessions declined over three years of the programme, from 78.7 ± 27.5 in unit I to 22.1 ± 35.6 (mean ± SD) in unit IX. A significant but weakly positive correlation was evident between attendance and achievement in pharmacology (r = 0.280; p < 0.0001). The mean score of the students who attended > 50% of the resource sessions was significantly higher (p < 0.0001). Students who attended ≤50% were more likely to achieve lower tertile scores. The mean score achieved and the number of higher tertile scorers were higher among students who attended > 50% of the resource sessions. Although female students' attendance was significantly higher, no significant gender-related differences in either mean scores or top grades achieved were found. CONCLUSIONS: In a PBL curriculum, the classroom attendance of students in pharmacology declined during the pre-clerkship phase. A weak positive correlation was found between attendance and academic achievement, as measured by MCQ test scores. Factors other than motivation and attendance may confound gender-based academic performance and merit further research.

Bio-thermal responses and heat balance of a hair coat sheep breed raised under an equatorial semi-arid environment.

Long-term assessments of bio-thermal responses in a hair coat sheep breed were performed to investigate the effect of the thermal environment on their physiological performance and thermal balance. Twelve healthy non-lactating Morada Nova ewes (3 ±â€¯1.2 years old, body mass 32.7 ±â€¯3.7 kg) were assigned in two 12 × 12 latin square designs (from 07:00 to 19:00 h and from 19:00 to 07:00 h, respectively) for assessments of their bio-thermal responses during 24 consecutive days. There was a monophasic pattern in the ambient temperature (TA), which ranged between 21 and 38 °C, thereby exposing the ewes to different levels of surrounding TA over the day and influencing several of their bio-thermal responses (P = 0.0001). Their body temperatures (i.e., rectal, skin, and hair coat surface temperatures) gradually increased (P = 0.0001) from 04:00 h. The mean peak for rectal temperature (39.3 °C) was recorded at 19:00 h, while for skin and hair coat surface temperatures it occurred at 13:00 and 14:00 h, respectively. The sensible heat loss by long wave radiation and surface convection exceeded the metabolism of ewes when the TA was below 24 °C, which usually occurred between 24:00 and 06:00 h. During exposure to higher ambient temperatures, the sheep increased respiratory evaporative heat loss, without panting. In conclusion, the sheep regulated rectal temperature within a relatively narrow range of 1.4 °C over 24 h, and appear to be well adapted to coping with heat. Minimum 24 h body temperature was correlated with minimum TA, indicating that heat conservation strategies are likely to be important for Morada Nova sheep in a tropical biotype at night, when rates of sensible heat loss exceed the heat generated by metabolism.

Erlotinib, cabozantinib, or erlotinib plus cabozantinib as second-line or third-line treatment of patients with EGFR wild-type advanced non-small-cell lung cancer (ECOG-ACRIN 1512): a randomised, controlled, open-label, multicentre, phase 2 trial.

BACKGROUND: Erlotinib is approved for the treatment of all patients with advanced non-small-cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We compared the efficacy of cabozantinib alone or in combination with erlotinib versus erlotinib alone in patients with EGFR wild-type NSCLC. METHODS: This three group, randomised, controlled, open-label, multicentre, phase 2 trial was done in 37 academic and community oncology practices in the USA. Patients were eligible if they had received one or two previous treatments for advanced non-squamous, EGFR wild-type, NSCLC. Patients were stratified by performance status and line of therapy, and randomly assigned using permuted blocks within strata to receive open-label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was done every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single-drug group to receive combination treatment. The primary endpoint was to compare progression-free survival in patients given erlotinib alone versus cabozantinib alone, and in patients given erlotinib alone versus the combination of erlotinib plus cabozantinib. We assessed the primary endpoint in the per-protocol population, which was defined as all patients who were eligible, randomly assigned, and received at least one dose of treatment. The safety analysis population included all patients who received study treatment irrespective of eligibility. This trial is registered with ClinicalTrials.gov, number NCT01708954. FINDINGS: Between Feb 7, 2013, and July 1, 2014, we enrolled and randomly assigned 42 patients to erlotinib treatment, 40 patients to cabozantinib treatment, and 43 patients to erlotinib plus cabozantinib treatment, of whom 111 (89%) in total were included in the primary analysis (erlotinib [n=38], cabozantinib [n=38], erlotinib plus cabozantinib [n=35]). Compared with erlotinib alone (median 1·8 months [95% CI 1·7-2·2]), progression-free survival was significantly improved in the cabozantinib group (4·3 months [3·6-7·4]; hazard ratio [HR] 0·39, 80% CI 0·27-0·55; one-sided p=0·0003) and in the erlotinib plus cabozantinib group (4·7 months [2·4-7·4]; HR 0·37, 0·25-0·53; one-sided p=0·0003). Among participants included in the safety analysis of the erlotinib (n=40), cabozantinib (n=40), and erlotinib plus cabozantinib (n=39) groups, the most common grade 3 or 4 adverse events were diarrhoea (three [8%] cases in the erlotinib group vs three [8%] in the cabozantinib group vs 11 [28%] in the erlotinib plus cabozantinib group), hypertension (none vs ten [25%] vs one [3%]), fatigue (five [13%] vs six [15%] vs six [15%]), oral mucositis (none vs four [10%] vs one [3%]), and thromboembolic event (none vs three [8%] vs two [5%]). One death due to respiratory failure occurred in the cabozantinib group, deemed possibly related to either drug, and one death due to pneumonitis occurred in the erlotinib plus cabozantinib group, deemed related to either drug or the combination. INTERPRETATION: Despite its small sample size, this trial showed that, in patients with EGFR wild-type NSCLC, cabozantinib alone or combined with erlotinib has clinically meaningful, superior efficacy to that of erlotinib alone, with additional toxicity that was generally manageable. Cabozantinib-based regimens are promising for further investigation in this patient population. FUNDING: ECOG-ACRIN Cancer Research Group, National Cancer Institute of the National Institutes of Health.

Assessment of heat tolerance and production performance of Aardi, Damascus, and their crossbred goats.

The question of whether the adaptability and production performance in goats may be enhanced using a crossbreeding program between bucks of a native and heat-tolerant breed and does of an exotic and dual-purpose breed was approached and examined herein by comparing purebred Aardi and Damascus goats and their crossbred lines (i.e., (1)/2 Aardi (1)/2 Damascus (½A½D) and (1)/4 Aardi (3)/4 Damascus (»A¾D)) reared in a region characterized by dry and hot bioclimatic conditions. Twenty-four male 6-month-old kids randomly segregated into four groups (six replicates/group) were used for the experiment. Climatic, thermo-physiological, biophysiological, metabolic, blood hematological, and biochemical measurements were all determined. The obtained results indicated that such a program was proven to be successful. This conclusion was demonstrated by the findings that crossbred goats (i.e., (1)/2A(1)/2D and (1)/4A(3)/4D) under such bioclimatic conditions were able to show (P < 0.05) higher heat tolerance capabilities compared to purebred Damascus goats as well as manifested (P < 0.05) higher production performance compared to the purebred Aardi goats. Accordingly, these evidences could emphasize that the crossbreeding may enable these animals to display a simultaneous improvement of both traits by the possible benefits that could arise from heterosis and breed complementarity. Researches dealing with this aspect may very well improve our understanding of goat's production and welfare under harsh environmental conditions. Future studies should include an economic analysis of traits that have the potential to impact the overall profitability to a vertically coordinated system.