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An entry point medial to the tip of the greater trochanter is considered optimal for antegrade femur nailing. The deforming forces in a subtrochanteric fracture often make it difficult to establish a perfect entry point during antegrade cephalomedullary nailing. To overcome this problem, we report a simple technique of making a retrograde entry portal for select difficult subtrochanteric fractures. The technique was used in 12 subtrochanteric fractures. Our indications were morbid obesity, revision nailing and atypical fractures. The technique involves creating a nail entry portal through the fracture from distal to proximal taking advantage of the abducted proximal fragment. Fracture reduction and nail insertion then proceeds in a standard manner. Additional reaming of the thick endosteal lateral cortex through the fracture was performed in atypical fractures. Satisfactory fracture reduction was achieved in all patients and 11 out of the 12 fractures united in the series. 1 patient developed an infected nonunion and was considered failure of treatment. The retrograde entry portal is a valuable alternative method that can be considered in nailing of difficult subtrochanteric fractures to establish an ideal entry point and nail trajectory.

Objectives To report surgical outcomes, palliative durability, and quality of life (QOL) after palliative robotic cystectomy (RC) for symptomatic advanced prostate cancer (PC). Methods Retrospective review of patients who underwent RC (n=10) at our institution from 2013-2018. European Organization for Research and Treatment of Cancer (EORTC) Functional Assessment of Cancer Therapy – Bladder Cystectomy (FACT-BL-CYS) questionnaire was administered to assess QOL. Patient characteristics, peri-operative outcomes, changes in pre-operative symptoms, and FACT-BL-CYS scores were assessed post-operatively. Results Mean age was 70 years (IQR, 64-72), and median follow up was 505 days. Five patients (50%) had prior radiation therapy (RT). Rates of perioperative and delayed complications were 30% and 30%, respectively. There were no cases of rectal injury. At latest follow up, there were no cases of urinary obstruction, hematuria, or pelvic pain, and 80% of patients remained symptom free. Six of ten patients responded to the questionnaire and completed the FACT-BL-CYS. Individual sub-domain scores (physical, social, functional, emotional, bladder specific) and overall scores were similar to post-operative radical cystectomy populations in other studies. 100% of responding patients would repeat RC. Conclusion RC appears to be a safe and effective option for advanced PC refractory to other interventions. The majority of patients would repeat the procedure. However, given the differences in goals of care for patients undergoing surgery for curative intent vs for palliation, we lack the ability to make true inferences regarding measurable improvements in quality of life; this highlights the need for high quality multi-institutional studies to better understand the impact of RC on QOL.

Background Metaphyseal fracture healing in the distal femur requires a stable biomechanical environment. The presence of arthritis-induced coronal-plane knee deformities can cause deviation of the mechanical axis, which results in asymmetric loading and increased bending forces in fractures of the distal femur metaphysis. This predisposes patients to nonunions or loss of fixation. Concurrent TKA during revision osteosynthesis might facilitate fracture healing, owing to its ability to correct coronal alignment, thereby restoring normal loading patterns at the fracture site, but to our knowledge, this has not been studied. Questions/purposes (1) Does TKA with concurrent revision internal fixation achieve fracture union in patients with coronal-plane deformity from knee arthritis and nonunion or loss of fixation in distal metaphyseal femoral fractures? (2) What is the survivorship and what are the short-term functional outcomes after these reconstructions? (3) What complications occur after these reconstructions? Methods Between 2015 and 2018, one surgeon treated 16 patients with a distal metaphyseal femur fracture nonunion and/or loss of fixation using concurrent TKA plus revision internal fixation. Autologous iliac crest bone grafting was performed in five patients with evident gaps at the fracture site. The indications for the procedure included patients older than 55 years of age presenting with a nonunion and/or loss of fixation of a distal metaphyseal femur fracture in the setting of painful Ahlback Grade III to V knee arthritis with an associated coronal-plane deformity. All patients meeting these indications were treated with this approach during the study period. Fracture union assessed by radiological bridging of at least three cortices, TKA survival free from revision due to any reason, coronal-plane correction using tibiofemoral angle, and patient mobility status assessed presurgery and at follow-up using the Parker mobility score (scored 0-9 points, with 9 indicating best mobility) were assessed by two surgeons who were not involved in the care of the study patients. Immediate and delayed complications were recorded. Patients were followed for a minimum of 24 months. The median (range) follow-up was 38 months (27 to 52 months). Results All fractures united after concurrent TKA plus revision internal fixation. In all, 14 of 16 fractures healed before 5 months, while the remaining two fractures united by 6 months. Survivorship analysis revealed a TKA component survival of 94% (95% CI 63% to 99%) at 52 months. The median (range) preoperative Parker mobility score of 5 points (3 to 8) improved to 7 points (2 to 9) at 12 months postoperatively and was maintained at last follow-up (p = 0.001). Four patients experienced complications; these were (1) prolonged surgical wound drainage resulting in debridement and polyethylene liner exchange, (2) deep knee infection needing a staged revision, (3) popliteal vein thrombosis, and (4) prolonged graft site pain. Conclusion Concurrent TKA plus revision internal fixation is effective for achieving union in patients with distal metaphyseal femur nonunion and loss of fixation in the setting of coronal-plane deformity induced by knee arthritis. Short-term TKA survival and improvement in patient mobility are excellent, although 4 of 16 patients in this report experienced complications, as one might expect with a procedure of this magnitude. Based on our results, correction of arthritis-induced coronal-plane knee malalignment can be considered part of the surgical strategy when treating such distal metaphyseal femur nonunions. Better preoperative evaluation of the deformity and control-based comparative studies can further validate the utility of this technique. Level of evidence Level II, therapeutic study.

Commercially used inorganic phosphors heavily depend on lanthanide doped host materials which are becoming more expensive and also their availability is limited due to scarcity. In this regard, a new lanthanide-free self-activated full-color emission phosphor in Y3+ doped Sr3 Bi(VO4 )3 system was developed by the conventional ceramic route. These phosphors crystallize into a hexagonal-type palmierite mineral structure. They exhibit broad excitation bands in the wavelength region of 250-400 nm, owing to the charge transfer transitions from both O2- and Bi6s2 electrons to V5+ . Upon excitation, these phosphors show bright broad emissions in the 400-750 nm wavelength range, peaking around 535 nm, with a large full width half maximum of 160 nm. The Y substitution allows tuning of the emission from yellowish green to bluish white due to increased distortion of [VO4 ]3- tetrahedron. Consequently, the CIE color coordinates changed from (0.42, 0.50) to (0.31, 0.35) which lies in the near-white region in the chromaticity diagram. Thus, the newly developed Y doped Sr3 Bi(VO4 )3 is a promising lanthanide-free full-color emission phosphor for applications in pc-white light emitting diodes.

Introduction: Classification is one of the most important research and applications of machine learning techniques Research in the area of human-machine interaction and machine learning contributed to the success of Chatbots Objective: This research concentrates on some of the most important developments in machine learning classification research and the issues of Coronavirus Disease 2019 (COVID-19) Since December 2019, COVID-19 has been causing a massive health crisis all over the world resulted in 5,418,237 confirmed and 344,201 death COVID-19 cases to date (24 05 2020) Clinical experts say that COVID-19 patients to be diagnosed in early-stage to save their lives Methods: This study attempted to detect COVID-19 patients who can recover from the disease, using machine learning techniques, so that suitable treatment can be given to the patients to save their lives Support Vector Machines (SVM), Artificial Neural Network (ANN), Decision tree, K-Nearest Neighbors (KNN), Random Forest and Logistic Regression algorithms are used to evaluate the classification performance Result and Conclusion: In this paper, a Chatbot was developed using the best algorithm evaluated to serve the society suffering from COVID-19 © IJCRR

Introduction: It is well known that the SARS-CoV-2 virus that causes COVID-19 could enter the human host through the oral cavity. In patients with periodontal disease, there is an increase of Furin, Cathepsin, and CD14+ CD16+ monocytes. The hypothesis stated here sheds light on the regular need of periodontal management to reduce inflammation and the levels of deleterious host enzymes and cytokines, which could pave the way for deadly viral diseases such as COVID-19. The Hypothesis: Patients with periodontal disease are at increased risk of SARS-CoV-2 infection due to elevated levels of Furin and Cathepsin in oral cavity and COVID-19 complications like cytokine storm could occur with increased frequency in patients with periodontal disease due to the significant increase of CD14+ CD16+ monocytes in blood. Evaluation of the Hypothesis: Oral and periodontal examination of patients with mild, moderate, and severe SARS-CoV-2 infection could shed light on the significant role played by periodontal disease in making an individual more prone to get SARS-CoV-2 infection by elevation of Furin and Cathepsin and the elevation of CD14+CD16+ monocytes and proinflammatory cytokines in the blood that could consequently worsen COVID-19 complications like cytokine storm. The blood counts of CD14+CD16+ monocytes need to be assayed in SARS-CoV-2 patients with and without periodontal disease to observe if periodontal disease as a coexisting condition elevates the proportion of CD14 CD16+ monocytes in SARS-CoV-2 patients. In fact, assessment of monocyte subsets in peripheral blood could be used as an immunosurveillance marker in SARS-CoV-2 patients. Hence, SARS-CoV-2 positive patients with chronic periodontal disease should be closely monitored for potential signs of a cytokine storm and its related complications.

Background In the setting of intra-articular distal radius fractures, the volar lunate facet (VLF) is the only articular segment that resists volar carpal subluxation. So, it is important to achieve a stable fixation of this key fragment. The VLF, when small (also called as volar marginal fragment, VMF) is located distal to the watershed line making fixation with the conventional volar locking plates difficult or impossible. Methods 18 patients with either an AO: 2R3B3 or a C3 fracture consisting of a VMF underwent surgical repair through a volar approach. The VMF was stabilised using a anatomical volar hook plate. Remaining fracture components were stabilised using 2.4/ 2.0 mm locked plates. Fracture healing, ability of the hook plate to maintain reduction of the VMF and complications were assessed during follow up. Functional outcome was evaluated using Mayo score and patient rated wrist evaluation questionnaires. Results All fractures united at follow up. Reduction of the VMF was maintained through healing with a stable radiocarpal and distal radioulnar joint. The mean flexion - extension wrist arc was 105° ± 10.2° The mean grip strength reached 74.6 ± 6% of the opposite side. The mean Mayo wrist score was 75 ± 5.3 and the mean patient rated wrist evaluation (PRWE) score was 15.2 ± 4.3 indicating recovery of wrist function. Conclusion It is important to identify VMFs in intra-articular distal radius fractures. Anatomically designed volar hook plate achieves excellent low-profile stable fixation of this key fragment to allow early mobilisation without fearing loss of reduction and volar carpal subluxation.

Accurate component positioning is the key for successful outcome after total hip arthroplasty (THA). Positioning acetabular and femoral components in a safe zone of 25°–50° on the basis of combined anteversion (CA) has shown to reduce instability and impingement. This safe zone was described for THAs performed through the posterior approach and has not been validated for other surgical approaches. Seventy patients who underwent unilateral uncemented THA were included in the study; 35 patients—using posterior approach and the remaining 35—using trans-gluteal approach. All patients included had a stable and impingement-free THA at a mean follow-up of 39.2 ± 9.5 months. CT scan was performed to assess component positioning by calculating CA. The values were compared between the two groups to study possible differences. CA in the trans-gluteal group was significantly lower (32° ± 3.7° vs 38.4° ± 4.6°, P

The paper confers the use of phytochemicals in resisting of several diseases caused by different microbes/pathogen. In the current scenario, there is a high demand for proven plant therapies, herbal drugs, and other natural products, as well as their therapeutic application, which are often found to be more effective than synthetic pharmaceuticals in chronic diseases. In many cases, plant extracts, herbal formulations, and phytochemicals perfectly supplement the typical therapy and at the same time do not cause side effects for example skin irritation, gastrointestinal problems. It is an urgent demand to find out complete therapeutic potential and adverse effects, of these phytochemical compounds because of the continued rise of drug‐resistant bacterial infections.

According to the state of food security and nutrition, Hunger has increased in many countries in which the economy has slowed down, mostly in middle-income countries. If nothing changes, the immense challenge of achieving the Zero Hunger Target by 2030. The causes of food scarcity might include factors such as unavailability of food due to less production of particular crops/vegetables (due to attack of pests/microbes), it becomes harder to fulfill the basic needs of life especially for poor. Therefore, we need to primarily focus on understanding the interaction between plants and microbes at the molecular level and underlying mechanisms of plant disease and which will help out to solve the global needs of food and resources. Plants have a natural defense mechanism/immune system to react to infections which subdivides into two parts. The first part identifies and reacts to molecules common to different classes of microbes, including non-pathogen. The function of the second part is to react to pathogens virulence factors, either directly or by affecting the host targets. We can also see the intricacies or reciprocation between plants and pathogen attackers. A vast and deep comprehension of plant defense mechanisms will defiantly solve the issue, like food scarcity.

Radiation dose intensification improves outcome in men with high-risk prostate cancer (HR-PCa). A prospective trial was conducted to determine safety, feasibility, and maximal tolerated dose of multilevel magnetic resonance imaging (MRI)-based 5-fraction SABR in patients with HR-PCa.This phase I clinical trial enrolled patients with HR-PCa with grade group ≥4, prostate-specific antigen (PSA) ≥20 ng/mL, or radiographic ≥T3, and well-defined prostatic lesions on multiparametric MRI (mpMRI) into 4 dose-escalation cohorts. The initial cohort received 47.5 Gy to the prostate, 50 Gy to mpMRI-defined intraprostatic lesion(s), and 22.5 Gy to pelvic lymph nodes in 5 fractions. Radiation doses were escalated for pelvic nodes to 25 Gy and mpMRI lesion(s) to 52.5 Gy and then 55 Gy. Escalation was performed sequentially according to rule-based trial design with 7 to 15 patients per cohort and a 90-day observation period. All men received peri-rectal hydrogel spacer, intraprostatic fiducial placement, and 2 years of androgen deprivation. The primary endpoint was maximal tolerated dose according to a 90-day acute dose-limiting toxicity (DLT) rate33%. DLT was defined as National Cancer Institute Common Toxicity Criteria for Adverse Events ≥grade 3 treatment-related toxicity. Secondary outcomes included acute and delayed gastrointestinal (GI)/genitourinary (GU) toxicity graded with Common Toxicity Criteria for Adverse Events.Fifty-five of the 62 enrolled patients were included in the analysis. Dose was escalated through all 4 cohorts without observing any DLTs. Median overall follow-up was 18 months, with a median follow-up of 42, 24, 12, and 7.5 months for cohorts 1 to 4 respectively. Acute and late grade 2 GU toxicities were 25% and 20%, while GI were 13% and 7%, respectively. Late grade 3 GU and GI toxicities were 2% and 0%, respectively.SABR dose for HR-PCa was safely escalated with multilevel dose painting of 47.5 Gy to prostate, 55 Gy to mpMRI-defined intraprostatic lesions, and 25 Gy to pelvic nodal region in 5 fractions. Longer and ongoing follow-up will be required to assess late toxicity.

Conveyor systems persist in being a source of injuries and fatalities in the mining industry. To reduce these incidents, better methods are needed to enhance the monitoring of probable hazards and improve situational awareness during the normal operation and maintenance of conveyor systems. To address these issues, researchers from the National Institute for Occupational Safety and Health (NIOSH) continue to investigate emerging technologies that show the potential to improve miner safety around conveyors. This paper presents a feasibility assessment by NIOSH researchers of a fully integrated, commercially available wireless Internet of Things (IoT) system to improve situational awareness around conveyor systems. Included are discussions of a full-scale laboratory test bed that was designed to simulate a working conveyor system as well as the challenges and successes of integrating the IoT system with the test bed.

Background: ESR1 mutations are acquired following ERα targeted therapies and are a major determinant of therapy-resistance. These ESR1 mutations maintain ESR1 signaling, albeit in a ligand-independent manner. Effective drugs targeting these mutant (MT) ERα proteins represent a significant unmet clinical need. We had previously shown that ERX-11, an ESR1-coregulator binding inhibitor, could block the function of these MT ERα proteins. In this study, we sought to leverage recently published structures of MT ERα to develop more potent analogues of ERX-11. Methods: Virtual screening of >250,000 derivatives of ERX-11 was performed with simulated docking on the MT ERα to identify and design analogues of ERX-11. Several hundred analogues were synthesized and tested in vitro using multiple BC model cells that express wild type (WT) ESR1 or mutant (MT) ESR1 (Y537S or D538G). Mechanistic studies were performed using RNA-Seq, Western blotting, qRT-PCR and reporter gene assays. The in vivo efficacy of the most potent ERX-11 analogue ERX-245 was examined using xenograft, PDX and metastatic models of MT-ER driven BC. Results: From our virtual and functional screen, we identified an ERX-11 analogue, ERX-245 as the most potent hit to target MT-ERα. Docking studies modeled a better fit of ERX-245 into the ligand binding domain of both the Y537S and D538G MT-ERα. ERX-245 potently reduced (IC50 ~250 nM) the cell viability of both WT-ERα and MT-ERα driven BC cells but not ERα negative BC cells. ERX-245 significantly reduced the growth (colony formation, clonogenic and mammosphere assays) of MT-ERα BC cells. ERX-245 exhibited synergistic activity in combination with CDK4/6 inhibitors. In distinction to classic SERDs like fulvestrant (which degrade ERα with in 4h), ERX-245 treatment decreased MT-ERα protein levels over 24 hours. PK studies indicated that ERX-245 is more polar and has better solubility and pharmacokinetic properties than ERX-11. ERX-245 reduced tumor growth of subcutaneous xenograft and PDX models driven by MT-ERα as well as the proliferation of xenograft derived MT-ERα explant models. ERX-245 significantly reduced the invasive capability of MT-ERα BC cells in vitro and inhibited both the metastatic capability and growth of metastatic tumors derived from MT-ERα BC cells injected by intracardiac or intratibial routes. Conclusions: Taken together, these results indicate that ERX-245 is a potent and pharmacologically translatable analog of ERX-11, with activity against both primary and metastatic tumors driven by MT-ERα. Citation Format: Ganesh V Raj, Suryavathi Viswanadhapalli, Karla Parra, Shihong Ma, Tae-Kyung Lee, Xihui Liu, Kara Kassees, Weiwei Tang, Junhao Liu, Zexuan Liu, Uday P Pratap, Behnam Ebrahimi, Rajeshwar Rao Tekmal, Jung-Mo Ann, Ratna K Vadlamudi. Development of a potent mutant-ESR1 targeted agent, ERX-245, for treating metastatic therapy-resistant breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS17-09.

Histone deacetylase inhibitors (HDACi) are identified as novel therapeutic agents, however, recent clinical studies suggested that they are marginally effective in treating triple negative breast cancer (TNBC). Here, we show that first-in-class Leukemia Inhibitory Factor Receptor (LIFRα) inhibitor EC359 could enhance the therapeutic efficacy of HDACi against TNBC. We observed that both targeted knockdown of LIFR with CRISPR or treatment with EC359 enhanced the potency of four different HDACi in reducing cell viability, cell survival, and enhanced apoptosis compared to monotherapy in TNBC cells. RNA-seq studies demonstrated oncogenic/survival signaling pathways activated by HDACi were attenuated by the EC359 + HDACi therapy. Importantly, combination therapy potently inhibited the growth of TNBC patient derived explants, cell derived xenografts and patient-derived xenografts in vivo. Collectively, our results suggest that targeted inhibition of LIFR can enhance the therapeutic efficacy of HDACi in TNBC., Li, Viswanadhapalli et al utilized multiple in vitro, ex vivo and in vivo models of TNBC to investigate LIFR inhibition. The authors reported that HDAC inhibition in TNBC cells led to an increase of LIFR expression and over activation of the downstream signaling elements (e.g., STAT3, mTOR, AKT), enhancing the aggressive potential of TNBC cells, and an LIFR inhibitor, EC359, synergistically enhanced the efficacy of HADC inhibitors in suppressing TNBC in vitro and in vivo.

Introduction: Giant cell tumor (GCT) most commonly involves distal femoral condyles, distal end of radius, proximal tibial plateau, and proximal humerus. GCT is uncommon to occur in small bones of hand and feet. 2% of GCT occur in hand. The incidence of GCT in foot is 1.2–1.8%. Only a few cases have been reported in literature worldwide. GCT is the most common cause of secondary ABC. We report a case of GCT of intermediate cuneiform in a 25-year-old female evolving into aneurysmal bone cyst (ABC). Case Report: A 25-year-old female presented to us with complaints of pain and swelling over the dorsum of right foot for a period of 1 year. On examination, there was a localized ovoid-shaped swelling of 2 by 2 cm over the dorsum of right foot. Radiographs revealed a well-defined osteolytic lesion in the intermediate cuneiform. T2 MRI showed hyper-intense lesion in intermediate cuneiform. The patient was taken up for surgery, and the intermediate cuneiform was excised completely. Removed bone was sent for histopathological examination which confirmed it to be GCT evolving into secondary ABC. The patient was followed for 1 year and had no complaints. The patient was able to weight bear and walk without any difficulty. There was no recurrence of lesion. Conclusion: GCT of the cuneiform evolving into ABC is a very rare presentation. The treatment of choice is excision of the tumor with or without bone grafting. Any osteolytic lesion in the small bones must be evaluated and should be intervened in the early stage. Keywords: Giant cell tumor, osteolytic lesion, surgical resection, intermediate cuneiform.

Optimal design and maintenance are necessary for the sustainability of wastewater treatment systems. In this study, we present the outcome of a novel approach to baseline assessment conducted prior to the design and deployment of a decentralized wastewater treatment system at a school in rural India. The baseline water quality monitoring protocol was deployed to assess (a) the quality and quantity of wastewater (greywater and blackwater) flows from the school and (b) the status of surface water and groundwater quality in the catchment. Hourly greywater flows and water quality trends were monitored across four seasons at the school. Average freshwater consumption at the school was 518 ± 322 L/day for hand washing and 287 ± 97 L/day for cooking meals. Greywater generation showed high hourly variations in COD levels. Greywater generated from hand wash and kitchen sources contributed to 110 g/day and 96 g/day of BOD5 respectively and 214 g/day and 141 g/day of COD respectively. Based on additional data from a self-reporting sanitation survey, the organic contaminant load generated from the toilet was estimated to be 1.5 ± 0.1 kg COD/day. At the catchment scale, both groundwater and surface water quality were monitored seasonally to assess the impact of raw sewage and stormwater inputs. Compared with borewells, high nitrate–N levels (> 10 mg/L) were observed in the village hand pump samples throughout the year. Maximum nitrate–N (16 mg/L) and fecal coliforms (3.9 log MPN/100 mL) levels were observed in surface waters during monsoons, indicating the impact of sewage and surface runoff on water quality. The proposed approach is useful to estimate data on freshwater use and wastewater generation at the school and hence to make the case for, and design of, a sustainable water management intervention.

INTRODUCTION AND OBJECTIVE:Radical nephroureterectomy (RNU) and cystectomy (RC) are commonly performed in urologic oncology, but their concurrent use is rare. Here, we report the perioperative and ...

Introduction: Fulvestrant is currently the only selective estrogen receptor degrader (SERD) that is approved for clinical use in estrogen receptor (ER) positive advanced breast cancer (ABC). The drug is approved as single-agent therapy in the first and second-line setting of metastatic ER-positive breast cancer. Areas covered: In this review, the authors review the preclinical studies that were pivotal in the development of fulvestrant, the pharmacologic properties of the drug, and the key clinical trials that resulted in its approval for clinical use. The authors discuss mechanisms of endocrine resistance and potential targets for endocrine refractory disease while highlighting ongoing studies that assess fulvestrant use with novel agents. Expert opinion: While fulvestrant has limited use in the first-line setting in advanced breast cancer, it is most frequently used in the second line after progression with aromatase inhibitors. The combination of fulvestrant with CDK4/6 inhibitors has shown a clear benefit over monotherapy in patients who progress on prior endocrine therapy. Further study is necessary to assess if patient outcomes can be enhanced by optimizing the sequence of endocrine therapies, targeting resistance pathways with novel agents, and development of new agents in the SERD class.

Alternative donor allogeneic hematopoietic cell transplants (HCTs), such as double umbilical cord blood transplants (dUCBT) and haploidentical related donor transplants (haplo-HCT), have been shown to be safe and effective in adult patients who do not have an HLA-identical sibling or unrelated donor available. Most transplant centers have committed to 1 of the 2 alternative donor sources, even with a lack of published randomized data directly comparing outcomes and comparative data on the cost-effectiveness of dUCBT versus haplo-HCT. We conducted a retrospective study to evaluate and compare the early costs and charges of haplo-HCT and dUCBT in the first 100 days at 2 US transplant centers. Forty-nine recipients of haplo-HCT (at 1 center) and 37 with dUCBT (at another center) were included in the analysis. We compared graft acquisition, inpatient/outpatient, and total charges in the first 100 days. The results of the analysis showed a significantly lower cost of graft acquisition and lower total charges (for 100-day HCT survivors) in favor of haplo-HCT. Importantly, to control for the obvious shortcomings of comparing costs at 2 different transplant centers, adjustments were made based on the current (2018) local wage index and inflation rate. In the absence of further guidance from a prospective study, the cost analysis in this study suggests that haplo-HCT may result in early cost savings over dUCBT and may be preferred by transplant centers and for patients with more limited resources.

Femoral neck nonunion in young patients has always been a difficult problem to deal with for surgeons. Numerous surgical procedures to address either the biological or mechanical issues at the nonunion have been described and most of them have been associated with variable results. Isolated biological augmentation is often associated with poor results and some techniques like vascularized grafting may require not so commonly available expertise. Valgus osteotomy is aimed to correct the abnormal fracture biomechanics associated with femoral neck fractures. By altering the nature of force transmission across the nonunion, shear forces are converted into compressive forces that lead to rapid osseous union without the need for bone grafting. Though the principles are sound and were described a long time ago, the technical aspects have evolved over time. Various modifications have been described to overcome shortcomings such as limb length discrepancy, reduction of femoral offset, alteration in mechanical axis, and the overall proximal femur anatomy. In this review, we look back at the fundamental principles and recent literature on the results of valgus intertrochanteric osteotomy for femoral neck pseudoarthrosis. We also highlight the important need for accurate preoperative planning and surgical execution. Lastly, we elaborate on the technical improvisations that have happened over time in order to improve functional results and to minimize complications and poor outcome after a valgus osteotomy.

Summary Background We report the clinical efficacy against COVID-19 infection of BBV152, a whole virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) in Indian adults. Methods We did a randomised, double-blind, placebo-controlled, multicentre, phase 3 clinical trial in 25 Indian hospitals or medical clinics to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Adults (age γ18 years) who were healthy or had stable chronic medical conditions (not an immunocompromising condition or requiring treatment with immunosuppressive therapy) were randomised 1:1 with a computer-generated randomisation scheme (stratified for the presence or absence of chronic conditions) to receive two intramuscular doses of vaccine or placebo administered 4 weeks apart. Participants, investigators, study coordinators, study-related personnel, the sponsor, and nurses who administered the vaccines were masked to treatment group allocation; an unmasked contract research organisation and a masked expert adjudication panel assessed outcomes. The primary outcome was the efficacy of the BBV152 vaccine in preventing a first occurrence of laboratory-confirmed (RT-PCR-positive) symptomatic COVID-19 (any severity), occurring at least 14 days after the second dose in the per-protocol population. We also assessed safety and reactogenicity throughout the duration of the study in all participants who had received at least one dose of vaccine or placebo. This report contains interim results (data cutoff May 17, 2021) regarding immunogenicity and safety outcomes (captured on days 0 to 56) and efficacy results with a median of 99 days for the study population. The trial was registered on the Indian Clinical Trials Registry India, CTRI/2020/11/028976, and ClinicalTrials.gov, NCT04641481 (active, not recruiting). Findings Between Nov 16, 2020, and Jan 7, 2021, we recruited 25 798 participants who were randomly assigned to receive BBV152 or placebo; 24 419 received two doses of BBV152 (n=12 221) or placebo (n=12 198). Efficacy analysis was dependent on having 130 cases of symptomatic COVID-19, which occurred when 16 973 initially seronegative participants had at least 14 days follow-up after the second dose. 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2–86·4). In the safety population (n=25 753), 5959 adverse events occurred in 3194 participants. BBV152 was well tolerated; the same proportion of participants reported adverse events in the vaccine group (1597 [12·4%] of 12 879) and placebo group (1597 [12·4%] of 12 874), with no clinically significant differences in the distributions of solicited, unsolicited, or serious adverse events between the groups, and no cases of anaphylaxis or vaccine-related deaths. Interpretation BBV152 was highly efficacious against laboratory-confirmed symptomatic COVID-19 disease in adults. Vaccination was well tolerated with no safety concerns raised in this interim analysis. Funding Bharat Biotech International and Indian Council of Medical Research.

Ultrasound-based arterial wall recognition and tracking methods in the literature apply to two-dimensional ultrasound data, either in the form of B-mode images or M-lines radio-frequency (RF) data. We propose a robust dynamic time warping method that is applicable to just one-dimensional single scan-line RF signals. It uniquely analyses the time-varying effects of tissue dynamics on the amplitude and phase features of the RF signals. Its performance was investigated via systemic in-vitro experiments on a pulsatile flow phantom. The recording was performed by an ultrasound imaging system where the B-mode video clips and the raw RF data were saved simultaneously for direct comparison of the proposed method’s versus B-mode reference measurements. The noise of different levels was added to the RF signals to evaluate the method’s robustness. The method detected the arterial walls in 95% -100% of the frames (with SNRs ≥ 10 dB), and for ~100% of those detections, the method accurately localized the walls in the frames. Even when SNR levels were poor (0 dB < SNR < 5 dB) the detection and correct rates were greater than 80% and 90%. The performance figures were consistent for different pulsation rates (0.4 to 3 Hz) emulated. Further, the tracking errors were < 5% for frames with SNR ≥ 5 dB, which improved (errors < 3%) with an increase in SNR. The distension measurements resulting from tracking were repeatable over continuous pulsation cycles (CoV < 0.5%) and were accurate compared to B-mode measurement, with RMSE = 22 μm. The measured versus reference distensions strongly correlated (r = 0.99, p < 0.05) to each other and yielding insignificant (p = 0.17) difference of -6 μm. The method has the potential to facilitate an automated framework for A-mode-based structural and functional analysis of the blood vessels. Therefore, it allows the realization of advanced and cost-effective real-time A-mode systems.

Introduction COVID-19 led to global disruption of healthcare and many students volunteered to provide clinical support. Volunteering to work was a unique medical education opportunity; however, it is unknown whether this was a positive learning experience. Methods The COVID Ready 2 study is a national cross-sectional study of all medical students at UK medical schools. We will compare opinions of those who did and did not volunteer to determine the educational benefit and issues they faced. We will use thematic analysis to identify themes in qualitative responses, in addition to quantitative analysis. Results The primary objective is to explore the effect of volunteering during the pandemic on medical education in comparison to those who did not volunteer. Our secondary objectives are to identify: whether students would be willing to assume similar roles in a non-pandemic setting; if students found the experience more or less beneficial than traditional hospital placements and reasons for this; what the perceived benefits and disadvantages of volunteering were; the difference in perceived preparedness between students who did and did not volunteer for foundation training year one and the next academic year; training received by volunteers; and to explore issues associated with volunteering, including safety issues and issues with role and competence. Conclusions We anticipate this study will help identify volunteer structures that have been beneficial for students, so that similar infrastructures can be used in the future; and help determine whether formal voluntary roles should be introduced into the non-pandemic medical curriculum.

Prostate cancer (PCa) and breast cancer (BCa) are both hormone-dependent cancers that require the androgen receptor (AR) and estrogen receptor (ER, ESR1) for growth and proliferation, respectively. Endocrine therapies that target these nuclear receptors (NRs) provide significant clinical benefit for metastatic patients. However, these therapeutic strategies are seldom curative and therapy resistance is prevalent. Because the vast majority of therapy-resistant PCa and BCa remain dependent on the augmented activity of their primary NR driver, common mechanisms of resistance involve enhanced NR signaling through overexpression, mutation, or alternative splicing of the receptor, coregulator alterations, and increased intracrine hormonal synthesis. In addition, a significant subset of endocrine therapy-resistant tumors become independent of their primary NR and switch to alternative NR or transcriptional drivers. While these hormone-dependent cancers generally employ similar mechanisms of endocrine therapy resistance, distinct differences between the two tumor types have been observed. In this review, we compare and contrast the most frequent mechanisms of antiandrogen and antiestrogen resistance, and provide potential therapeutic strategies for targeting both advanced PCa and BCa.

Rice is the most significant cultivated harvests everywhere throughout the world, specifically in Asian nations. Nowadays the evaluation of rice quality has a great impact on the market due to adulteration by plastic rice and stones. The assessment of rice is prepared physically by experienced a rancher which is a tedious and monotonous errand and in particular it is a dangerous strategy where the rice might be pulverized by growth pollution. In this paper, a quick, programmed and non-destructive assessment practice is endeavored to measure the nature of rice based on deep learning neural system model. The pre-processing is started by the Median channel to expel noises from the input pictures. By utilizing Fuzzy c-means clustering, the edges of the rice pictures are appropriately depicted. The features like contour, edge, and region are chosen with the assistance of a genetic algorithm. A probabilistic neural system is created to characterize the portioned rice picture. The presentation of PNN model is introduced to show its viability with regards to exactness, accuracy, f-score, and review, and the outcomes are compared with the existing SVM method.

Background: Ultrasonographic imaging to record changes in peripheral arterial diameter associated with Flow mediated dilatation or Low flow mediated constriction is routinely used to assess various facets of vascular endothelial function. Imaging poses many challenges including requirement of costly ultrasound machines, trained manpower to perform imaging and effort-intensive steps to analyse the images subsequently using manual or automated methods. We tested the feasibility and validity of using an imaging-free technology to record resting arterial diameters of brachial and radial arteries. Methods: Eight healthy volunteers initially underwent ultrasonographic imaging (M7, Mindray; Shenzhen, P.R. China) of brachial artery and proximal radial artery. The brachial and radial artery ‘zones’ thereby identified through imaging were surface marked on subject’s arm. Imaging-free ARTSENS® Pen device [1] (Healthcare Technology Innovation Centre, IIT Madras, India) consisting of highly integrated hardware for operating a single element broadband ultrasound transducer (centre-frequency = 5 MHz, spatial half angle

Background: Arterial stiffness index (β) is a clinically accepted vascular metric, calculated from arterial pressure and diameter obtained simultaneously from a single arterial site [1]. Hence, accurate measurement of β can only be performed on arteries where pressure can be recorded along with the diameter. We present a method to evaluate β from superficial arteries using arterial force (F) and diameter (D) waveforms, employing mathematical models (shown below) exploiting the non-linear pressure-diameter relationship [2], without requiring absolute pressure. Methods: Pilot functionality assessment was performed on eight participants (24 ± 5 years). A custom-developed frequency-matched system, combining single-element ultrasound and force-sensing transducers, was used to measure D and F waveforms from the common carotid artery. A hemodynamic-loop was formed from these measures and optimised to eliminate viscous components, and evaluate the elastic stiffness index β. Traditional β-formula [2] yielded reference values for comparison. fe(t)=fmx×(eβ(D(t)Dd−1)−1eβ(DsDd−1)−1) fe(t): Viscosity eliminated arterial force fmx: Maxima of viscosity eliminated arterial force β : Stiffness index D(t): Arterial diameter Ds: Systolic diameter Dd: Diastolic diameter Results: The system captured high fidelity D and F waveforms, adequate for reliable β evaluation. Measured group-average β (4.7 ± 0.8) was concurrent with literature. The measured β values statistically agreed (LoA = ±0.83 and bias = –0.32; non-significant p > 0.05) and strongly correlated (r = 0.93, p < 0.001) with the reference values. Further, they exhibited acceptable beat-to-beat repeatability (variation

OBJECTIVE To evaluate the legacy of endocrinologist Jean Wilson, whose discovery in 1969 of 5 alpha-reductase (5AR) and description of dihydrotestosterone (DHT) as the primary hormone associated with prostatic growth ushered in a golden age of collaboration between endocrinologists, oncologists, and urologists that led to some of the critical discoveries in the understanding and treatment of prostatic pathology. MATERIALS AND METHODS A review of the medical literature between 1969 and 2020 was conducted and multiple authors interviewed. RESULTS In 1969, Gloyna and Wilson demonstrated the reduction of testosterone to DHT in the prostate. With Bruchovsky, Wilson established that DHT was the primary hormone associated with prostatic growth. Wilson went on to show that androgens are involved in every aspect of prostate development, growth, and function. Wenderoth and Wilson then showed that a 5AR inhibitor blocked the prostatic growth. Subsequently, clinical trials with therapies targeting 5AR were led by Roehrborn and McConnell. Tilley and Wilson with Marcelli and McPhaul cloned the human androgen receptor at UT Southwestern in 1989 and provided the first evidence that androgen receptor was a transcriptional factor that could regulate its own expression in prostate cancer. Androgen receptor mutations explaining the molecular basis of androgen resistance syndromes were first described by Wilson, McPhaul, et al in the early 1990s. CONCLUSION Basic, translational, and clinical research has played a pivotal role in our current understanding of prostatic disease. Much of this legacy is credited to Jean Wilson and the cross-pollination of world-class scientists across fields, whom he inspired.

Safe surgical dislocation with a trochanteric flip osteotomy has been shown to be a reliable technique that provides excellent exposure for treating femoral-head fractures with minimal complications. This technique also allows associated labral injuries and acetabular fractures to be treated through the same approach. DESCRIPTION: The procedure is performed with use of a conventional Kocher-Langenbeck exposure with the patient in the lateral position. The trochanteric flip is performed, allowing exposure of the anterior capsule, which is incised to dislocate the head anteriorly. Fracture fixation is performed with use of mini-fragment screws followed by relocation of the head, closure of the capsulotomy, and fixation of the osteotomy. ALTERNATIVES: Fixation of femoral-head fractures can also be performed with use of alternate surgical approaches. Anterior-based surgical approaches like the Hueter approach or the Smith-Petersen approach are preferred with the goal of preserving the posterior extraosseous blood supply to the femoral head. The posterior Kocher-Langenbeck approach can also be utilized because there is no clear evidence suggesting that a properly performed posterior approach affects the blood supply of the femoral head. RATIONALE: Surgical hip dislocation is 1 of the preferred techniques for operative treatment of femoral-head fractures and is a versatile approach that provides circumferential exposure of the femoral head and acetabulum through an anterior dislocation. A compromised blood supply to the femoral head is much less likely with use of this approach compared with posterior-based surgical approaches. Compared with anterior-based surgical approaches, which are often restrictive, surgical dislocation is extensile and provides adequate exposure to treat associated injuries to the acetabulum and the labrum of the hip. EXPECTED OUTCOMES: Outcomes following surgical dislocation for femoral-head fractures are reportedly good to excellent in >80% patients. Urgent reduction of the hip joint followed by anatomical reduction of the fracture and stable fixation of the fracture and osteotomy leads to predictably good results. Notable complications include heterotopic ossification, which has been reported in up to 60% patients, as well as osteonecrosis of the femoral head (often related to the initial injury rather than the approach) and degenerative arthritis of the hip joint. IMPORTANT TIPS: The Gibson interval may be utilized to preserve the gluteus maximus. Identify all of the posterior structures starting proximally from the posterior border of the gluteus medius, and continuing to the piriformis, triceps coxae, quadratus femoris, and the vastus lateralis. Aim for a thickness of 1 to 1.5 cm when performing the osteotomy; an osteotomy that is either too thick or too thin can negatively affect outcomes. The osteotomy should begin just anterior to the posterior fibers of the gluteus medius to ensure that the osteotomy is anterior to the piriformis tendon. It should exit distally to the vastus lateralis origin. Carefully elevate the posterior margin of the gluteus minimis from the capsule to avoid the tethering effect during anterior translation of the osteotomized fragment. Capsular tears during the initial dislocation are common and should be incorporated into the anterior capsulotomy. Repair of large posterosuperior labral tears may improve outcomes. Fixation of the fracture can be performed with mini-fragment screws or headless screws. Non-fixable small fragments can be excised. The osteotomy should be reduced and fixed in a stable manner to prevent trochanteric nonunion and preserve abductor function.

PURPOSE Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services. METHODS A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider). RESULTS Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing—initial testing of priority genes followed by expanded testing—was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM, for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM, and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches. CONCLUSION This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

BackgroundResistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a significant clinical problem. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis. A benzothiazole-based glutamate release inhibitor with several context-dependent mechanism(s) of action, Riluzole has shown anti-tumor activity in multiple malignancies, including melanoma, glioblastoma, and breast cancer. We previously reported that the acquisition of Tamoxifen resistance in a cellular model of invasive lobular breast cancer is accompanied by the upregulation of GRM mRNA expression and growth inhibition by Riluzole.MethodsWe tested the ability of Riluzole to reduce cell growth, alone and in combination with endocrine therapy, in a diverse set of ER+ invasive ductal and lobular breast cancer-derived cell lines, primary breast tumor explant cultures, and the estrogen-independent,ESR1-mutated invasive lobular breast cancer patient-derived xenograft model HCI-013EI.ResultsSingle-agent Riluzole suppressed the growth of ER+ invasive ductal and lobular breast cancer cell linesin vitro, inducing a histologic subtype-associated cell cycle arrest (G0-G1 for ductal, G2-M for lobular). Riluzole induced apoptosis and ferroptosis and reduced phosphorylation of multiple pro-survival signaling molecules, including Akt/mTOR, CREB, and Src/Fak family kinases. Riluzole, in combination with either Fulvestrant or 4-hydroxytamoxifen, additively suppressed ER+ breast cancer cell growthin vitro. Single-agent Riluzole significantly inhibited HCI-013EI patient-derived xenograft growthin vivo, and the combination of Riluzole plus Fulvestrant significantly reduced proliferation in primary breast tumor explant cultures.ConclusionsRiluzole, alone or combined with endocrine therapy, may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer.

OBJECTIVES To compare outcomes after surgical treatment of Pipkin I and II femoral head fractures treated with either a surgical dislocation (SD) or a direct anterior approach (the modified Heuter approach). STUDY DESIGN Retrospective, multicentre. SETTING Three Level I trauma care centers. PATIENTS Fourty-nine patients operated for Pipkin types I or II femoral head fractures. Twenty-seven using SD and 22 using the modified Heuter approach. INTERVENTIONS Initial closed reduction of the joint followed by open reduction and internal fixation of the fracture/fragment excision. Fixation was performed using headless or countersunk mini fragment screws. OUTCOME MEASUREMENTS The 2 groups were compared for (1) perioperative measures: blood loss, surgical time, pain [visual analog scale (VAS)], and length of hospital stay; (2) radiological outcome in terms of fracture union, occurrence of posttraumatic hip arthritis, and femoral head osteonecrosis; and (3) functional outcome using the modified Merle d' Aubigne score and Oxford hip scores. RESULTS Surgical time, blood loss, and VAS at 24 hours were significantly lower in the modified Heuter group. The VAS at discharge and length of stay were similar in both groups. All fractures had united. No cases of osteonecrosis were observed. Functional outcome and complications were similar in both groups. CONCLUSIONS Both SD and the modified Heuter approach are effective in treating patients with Pipkin I and II femoral head fractures with comparable radiological and functional outcomes. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Estrogen receptor-positive (ER+) breast cancer is the most commonly diagnosed form of this malignancy. Aromatase inhibitors and selective estrogen receptor modulators or degraders (SERMS, SERDs) can be highly effective in treating ER+ breast cancer, but de novo and acquired resistance to these interventions is a persistent clinical problem. Endocrine therapy resistant breast cancer cells rewire their metabolism to support cellular demands associated with rapid proliferation and/or increased invasion and metastasis. An important feature of this metabolic flexibility is conversion of glutamine to glutamate, an amino acid integral to protection of cells from oxidative stress. Consistent with this, we show multiple cellular models of ER+, endocrine resistant breast cancer cells markedly increase glutamate release and upregulate expression of essential glutamine/glutamate metabolic enzymes and transporters, including the glutamate/cystine antiporter xCT, glutamate dehydrogenase (GLUD1/2), and/or the glutamine importer SLC1A5. Riluzole (RIL) is FDA-approved for the treatment of amyotrophic lateral sclerosis (ALS), and has several proposed mechanisms of action, including suppression of glutamate release and increased glutamate uptake. We show ER+, endocrine responsive and resistant breast cancer cells are growth-inhibited by RIL. This is due to an increase in cell death, particularly in endocrine resistant breast cancer cells, and cell cycle arrest. Interestingly, histologic subtype confers a different cell cycle arrest profile, with invasive ductal cancer (IDC) models arresting in G1 but invasive lobular cancer (ILC) models arresting in G2/M. Isobologram analysis of RIL plus SERMs or SERDs shows additive-to-synergistic activity in a subset of ER+ cell line models, and preliminary studies show combination activity in patient-derived explants (PDEs). Mechanistically, we tested whether signaling through metabotropic glutamate receptors (mGluRs, GRMs) and/or cystine import contribute to RIL’s growth-inhibitory phenotype. Antagonists of mGluRs/GRMs don’t phenocopy the effects of RIL, suggesting extracellular glutamate signaling through these receptors is not a key mechanism. Rescue experiments with β-mercaptoethanol to promote cystine uptake through transporters other than xCT show partial reversal of RIL-mediated cell cycle arrest in some cells, suggesting xCT may contribute to RIL-induced growth inhibition. In summary, we show RIL may be a viable addition to endocrine therapy in ER+ breast cancer. Ongoing studies will test additional mechanism(s) by which RIL may attenuate the growth of ER+ breast cancer models in vitro, including inhibition of protein kinase C and casein kinase 1 delta. We are further testing RIL efficacy alone and in combination with a SERD in primary tumors and lung metastases in a ER+ patient-derived xenograft (PDX) model.

The treatment and management of prostate cancer continues to evolve; newer classes of agents and combination therapies are being developed and some are being investigated in early phase clinical trials.We discuss investigational hormonal agents for the treatment of prostate cancer and focus primarily on luteinizing hormone releasing hormone (LHRH) agonists in early stage trials. We look at agents that target the hormonal axis, including anti-androgens, gonadotropins, estrogenic agents and progestogenic agents and other non-hormonal agents often used in combination with LHRH agonists. We review these candidates in the specific clinical niche in which they might find utility.Of all candidate compounds being evaluated in clinical trials, very few will receive FDA approval. Few, if any of the investigational agents discussed here will be used routinely in clinical practice for treating prostate cancer. Recognizing the reasons for the failure of agents to advance to later stage trials is important. Furthermore, a thorough understanding of the mechanisms underlying prostate cancer pathogenesis, including various points in the HGPA and parallel pathways, will help identify potentially actionable targets.

In recent years latent heat energy storage (LHES) has received a worldwide focus in the area of solar still applications. Among various techniques available to improve the productivity of solar stills, heat storage is one of the proverbial areas in the present scenario. LHES surpasses sensible heat energy storage (SHES) in solar still applications owing to its properties like latent heat, thermal conductivity, etc. Focus has to be given in the selection of suitable LHES material since its properties are very significant during the performance and operation of solar stills. Though previous reviews on LHES in solar stills focus only on the productivity enhancement, this paper presents an up to date comprehensive review exclusively about LHES in solar stills focusing on its productivity, properties of LHES materials and the mechanisms behind the variation in properties of LHES materials. Further, in addition to this, a detailed analysis is also presented in this paper by employing analytical hierarchy process (AHP) which enable the researchers to prioritize the properties during the selection of LHES in solar still applications. Besides AHP analysis, we also evaluate the relative efficiency of the available LHES materials for solar still application by data envelopment analysis (DEA) to find the frontier LHES materials thereby suggesting the methods to augment the properties of the frontier material (identified through DEA analysis). Thus, this paper may be a reference guide in the near future for the academicians, researchers to get an overview about the various LHES materials used in solar stills and significance of their properties for improving the yield in solar still applications.

Objectives To determine the implications of different prostate sampling schemes on the diagnosis of clinically significant prostate cancer (csPCA, ISUP group 2–5) and clinically insignificant prostate cancer (ciPCA, ISUP group 1) in men with abnormal multiparametric magnetic resonance imaging (mpMRI) undergoing MRI-transrectal ulrasound fusion targeted biopsies. Materials and Methods This is a retrospective analysis of a cohort including all men who had a single lesion on mpMRI of the prostate performed between January 2016 and June 2017. All men underwent an MRI-transrectal ulrasound fusion biopsy and systematic (SBx) sampling of the prostate, which combined and were considered the standard of reference. The hypothetical 3 biopsy sampling schemes were defined as follows: Targeted biopsy only (TBx), TBx + ipsilateral SBx (ipsi-SBx) and TBx + contralateral SBx (contra-SBx) and were evaluated for the detection of csPCA and ciPCA. Sensitivity and 95% intervals were calculated, McNemar test was used to compare sensitivities between the various sampling schemes. Results TBx + SBx detected csPCa in 47% (55 of 116) of the 116 men who met eligibility criteria. Sensitivity and 95% confidence intervals for csPCa detection was 85.5% (73.3%–93.5%), 96.4% (87.5%–99.6%), and 92.7 (82.4%–98%) for TBx alone, TBx + ipsi-SBx and TBx + contra-SBx, respectively. csPCa detection rates were higher for both TBx + ipsi-SBx and TBx + contra-SBx compared to TBx alone. Clinically insignificant cancers alone were detected in 7.7% (9 of 116), 10.3% (12 of 116), and 14.6% (17 of 116) of the cohort by TBx only and TBx + ipsi-SBx, and TBx + contra-SBx, respectively. Conclusions TBx + ipsi-SBx may increase the detection of csPCa while limiting overdiagnosis of indolent cancers.

Background: Radiofrequency probes have been used extensively in various arthroscopic procedures. Measurable cartilage damage occurs after radiofrequency probe application. However, the histological changes of cartilage damage following radiofrequency chondroplasty have not been extensively studied. Materials & Methods: Articular cartilage specimens were obtained from patients undergoing total knee replacement surgeries. Radiofrequency probes were applied at 1, 3 and 5 seconds and samples were sent to histopathology laboratory. The histological changes of cartilage damage were analyzed using the International Cartilage Repair Society (ICRS) assessment scale. Safranin O staining was done to assess the proteoglycan content. Results: Histologically measurable articular cartilage damage occurs after radiofrequency probes Conclusions: The time of application of radiofrequency probes should be optimized so as to minimize cartilage damage.

T cell–replete post-transplant cyclophosphamide (PTCy)-based protocols have led to increasing use of haploidentical allogeneic hematopoietic cell transplantation (haploHCT). With this approach, bidirectional alloreactivity causing nonengraftment or severe graft-versus-host disease (GVHD) is no a longer major barrier to haploHCT. PTCy eliminates alloreactive lymphocytes but spares CD34+ stem cells and regulatory T lymphocytes, resulting in reliable hematopoietic recovery with relatively low incidence of GVHD. The immediate post-haploHCT course, usually before PTCy administration, is often complicated by cytokine release syndrome (CRS). The predictors of CRS and its effect on outcomes post-transplant have not been fully ascertained. We analyzed the outcomes of 66 patients who received haploHCT at our institution. Using published CRS criteria we identified 48 patients who developed CRS. In multivariate analysis peripheral blood grafts were significantly associated with grade ≥ 2 CRS, compared with bone marrow. Grade ≥ 2 CRS (compared with grade

BACKGROUND: Recently,CDK4/6 inhibitors in combination with endocrine therapy (AE/AI/SERDs) is approved for the treatment of ER+ advanced breastcancer (BCa). However, not all patients benefit from CDK4/6 inhibitors therapy. Emerging studies indicate many therapy-resistant tumors retainER signaling, via interaction with critical oncogenic coregulatorproteins. Considering complex signaling interplay of ER and CDK4/6 axis, combination therapy of CDK inhibitor with other potent ER-targeted agents that block ER coregulatory signaling may extend the efficacy and may prevent the development of resistance to the CDK4/6 inhibitors. We recently developed a small organic molecule, ER coregulator binding modulator ERX-11 (EtiraRx-11). The objective of this study is to test the utility of novel combination therapy of ERX-11 with CDK4/6 inhibitor palbociclib in treating therapy resistant advanced BCa. METHODS: We have utilized multiple therapy sensitive and therapy-resistant BCa models with various genetic backgrounds. We tested efficacy using both acquired resistance and engineered models that express ER mutations or oncogenes. Efficacy of combination therapy was tested using established in vitro assays including, MTT, colony formation, apoptosis, and cell cycle progression. Mechanistic studies were conducted using reporter gene assays, gene expression, RNA-seq analysis and signaling alterations. Patient-derived BCa explant and Xenograft studies were used to determine the in vivo efficacy of the combination therapy. RESULTS: ERX-11 effectively blocked ER-mediated and ER-coregulator mediated oncogenic signaling and has potent anti-proliferative activity against both endocrine therapy-sensitive and therapy-resistant BCa cells. Mechanistic studies using IP-Mass spectrometry showed that ERX-11 blocks the interaction between a subset of coregulators with ER in resistant BCa models. ERX-11 exhibited potent anti-proliferative activity against therapy-sensitive and therapy-resistant ER-driven BCa cells in vitro, in xenograft models in vivo and in patient-derived breast tumor explants ex vivo. Co-treatment of ERX-11 with palbociclib synergistically reduced cell viability and induced apoptosis of therapy sensitive and resistant BCa model cells. Importantly, combination therapy of ERX-11 and the palbociclib synergistically reduced the growth and induced apoptosis of tamoxifen and letrozole resistant xenograft tumors compared to either drug alone. RNA-seq studies revealed that combinational treatment with ERX-11 and palbociclib uniquely activated p53 and unfolded response mediated apoptotic pathways and suppressed E2F and Myc target genes. Biochemical studies confirmed combination therapy significantly altered E2F1 and ER signaling pathways and promoted apoptosis. CONCLUSIONS: Our data support a critical role of blocking ER coregulator signaling in treating therapy resistance in advanced ER+ BCa. Combinational treatment with ERX-11 and palbociclib may overcome/delay endocrine therapy resistance. Citation Format: Viswanadhapalli S, Sareddy GR, Zhou M, Ali E, Li X, Ma S-H, Lee T-K, Tekmal RR, Ahn J-M, Raj GV, Vadlamudi RK. Blocking ER coregulator signaling enhances CDK4/6 inhibitor palbociclib therapy in ER-positive advanced breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-09-06.

Objective To describe epidemiologic patterns, stage at presentation, histology, and treatment differences associated with Hispanic men diagnosed with testicular germ cell tumor (TGCT). Hispanics are the fastest growing demographic in the United States and reports suggest that the incidence of TGCT is rising most rapidly in this demographic, yet little is known about TGCTs in Hispanic patients. Materials and Methods We compared patient factors, tumor characteristics, treatment patterns, and outcomes of non-Hispanic white (NHW) vs Hispanic patients at our own institution in North Texas from 2010 to 2016. The findings were corroborated by analyzing the National Cancer Database testicular cancer registry from 2004 to 2014. Results We identified 154 patients with TGCT at our institution, of which 89 were NHW (56.0%) and 65 were Hispanic (40.9%). A review of the National Cancer Database identified 49,607 NHW patients (81.5%) and 6724 Hispanic patients (11.0%) diagnosed with TGCT. At presentation, Hispanic patients were approximately 5 years younger than NHW patients, delay seeking care for testicular cancer, were more likely to have nonseminomatous histology, had a larger tumor size, and had a higher disease burden at presentation. Additionally, we identified differences in treatment patterns at the national level. Conclusion Differences in outcomes and treatment patterns of Hispanic and NHW patients with TGCT may represent underlying socioeconomic issues and access to care; however, discrepancies in age of onset and histology of TGCT between Hispanic and NHW patients may signify differences in tumor biology or risk factors. We suggest that this possibility be explored further as we embark upon the genomic classification of TGCT.

Desalination using solar stills is an ancient economic method for water desalination. Over the years, research and development in the area of solar still has resulted in increased distillate yield by means of integration of PCM (phase change material), photo-voltaic thermal (PVT), etc with the still. Nano-PCM is an upcoming technology which modifies the thermal performance of PCM. The aim of this research is to analyze the efficiency of 20 solar stills including nano-PCM based solar stills considering various input and output criteria using integrated fuzzy analytical hierarchy process (AHP) and data envelopment analysis (DEA). The efficiency derived here is relative with regard to the parameters and stills considered in this study. The result infers that, even though the productivity of stepped solar still with sun tracking system was high, but when techno-economic aspects were considered it is not among the top solar stills. The analysis indicated pyramid type solar still, single slope solar still with PVT, solar still with NPCM (paraffin + copper oxide), solar still with NPCM (paraffin + titanium dioxide) and solar still with PCM (paraffin) occupies the top five positions with relative efficiency of 100, 100, 88.47, 88.46 and 76.93% respectively.

This paper describes the design of a real-time non-contact vibration measurement system which can be used to measure both amplitude and frequency of vibration accurately in two dimensions (X-Y plane). This measurement scheme is optical in nature and uses 2D position sensitive detector (PSD) as the primary sensor for measuring the displacement amplitude of vibration directly. For the first time, to the best of our knowledge, a micro-electro-mechanical systems (MEMS) digital accelerometer is integrated on the same platform where the PSD is mounted to nullify the effect of self-vibration. The complete measurement system is configured over National Instruments-field programmable gate array (NI-FPGA), which enables it to be entirely digitalized, stand alone and reconfigurable. The entire system is enabled to be remotely monitored on a mobile phone with the help of NI-Data dashboard android application within the effective range of a Wi-Fi network. This system can very accurately measure the vibration frequency from 20 Hz to 800 Hz for minimum peak to peak amplitude of 6.36 μm along X-axis and 8.54 μm along Y axis with a maximum 0.058% error in measured frequency.

A smart city is defined as a sustainable and efficient city center providing high quality of life by optimally using its resources. Managing its resources especially energy is a very crucial factor owing to the complexity of various interlinked parameters. In this paper, the importance of various criteria for sustainability in a smart city are determined using fuzzy and fuzzy-AHP method. The sustainability indicators for designing a smart city in a developing country has been identified. DEA:AR-CCR model is adopted to determine the relative efficiency of each of the sustainability indicators for a smart city in the context of input and output criteria. The decomposition efficiency measures clearly highlight which sustainability indicator the country needs to focus based on the importance of the input criteria to achieve the desired outputs. It was found policy makers and administrators have to design policies for economic development (0.85) and energy (0.82) for achieving economic prosperity of the nation.

The overall recurrence rate of T1 renal cell carcinoma is low. We evaluated abdominal imaging after partial nephrectomy based on current guidelines for T1 renal cell carcinoma surveillance.We retrospectively reviewed the records of patients with T1 renal cell carcinoma who underwent partial nephrectomy between 2006 and 2012 followed by abdominal imaging at our institution. Primary and secondary outcomes were the incidence and timing, respectively, of imaging diagnosed abdominal recurrences. A literature review was performed to summarize prior reports of recurrence incidence and timing after partial nephrectomy for T1 disease.A total of 160 patients with stage T1a and 37 with T1b underwent partial nephrectomy. Seven patients had an abdominal recurrence, including 3 with local and distant recurrences, and 4 with a metachronous contralateral kidney recurrence. The incidence of abdominal recurrence detected by imaging was higher in the T1b than in the T1a group (10.8% vs 1.9%, p = 0.024). Although it was not significant, median time to recurrence was earlier in T1b vs T1a cases (13 vs 37 months, p = 0.480). In each group recurrences developed after 3 years of suggested guideline surveillance. In the literature combined with the current study the time to median recurrence for T1b vs T1a was 24 vs 29 months (p = 0.226).Recurrences detected by abdominal imaging developed earlier and more frequently in T1b than in T1a cases. Future recommendations for surveillance strategies after partial nephrectomy should distinguish T1a from T1b with less intense frequency of imaging for T1a. A longer period of surveillance should be considered since recurrences can develop beyond 3 years.

New high IR reflecting yellow pigments are developed in BiVO 4 -CaMoO 4 powellite type system. The resulting colorants were characterized for their structural as well as optical properties. These solid solutions allow fine tuning of the band gap resulting various shades of yellow hues with high IR reflectance. The yellow hue component ( b*) values have been significantly improved to 75.7 in the solid solutions of (BiV) x (CaMo) 1- x O 4 than that of BiVO 4 . Application study of selected pigments on concrete cement substrate demonstrate their coloring as well as IR reflective property. These pigments exhibit strong chemical stability and light resistance. Thus the developed pigments are potential candidates as environmentally friendly cool pigments for roofing applications.

Novel molybdenum based pyrochlore type red emitting phosphor materials: NaGd 1 −x SnMoO 7 : x Eu 3+ were prepared by the conventional solid state route. The developed phosphors were characterized for their structure as well as luminescent properties. The NaGd 1 −x SnMoO 7 : x Eu 3+ phosphors show strong red emission at 615 nm corresponding to the forced electric dipole transition 5 D 0 → 7 F 2 under near-UV and blue excitation. Further these phosphors exhibit high color purity characterized by sharp red emissions ( fwhm ~6 nm) with high asymmetric ratio. The color coordinates of all the samples under 393 nm excitation were calculated and found to be (0.65, 0.35) which are comparable to the standard color coordinates for red (0.67, 0.33). Thus the synthesized phosphors could be suitable red candidates in phosphor converted white light emitting diode applications.