Efficient and targeted COVID-19 border testing via reinforcement learning.

Throughout the coronavirus disease 2019 (COVID-19) pandemic, countries have relied on a variety of ad hoc border control protocols to allow for non-essential travel while safeguarding public health, from quarantining all travellers to restricting entry from select nations on the basis of population-level epidemiological metrics such as cases, deaths or testing positivity rates1,2. Here we report the design and performance of a reinforcement learning system, nicknamed Eva. In the summer of 2020, Eva was deployed across all Greek borders to limit the influx of asymptomatic travellers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and to inform border policies through real-time estimates of COVID-19 prevalence. In contrast to country-wide protocols, Eva allocated Greece's limited testing resources on the basis of incoming travellers' demographic information and testing results from previous travellers. By comparing Eva's performance against modelled counterfactual scenarios, we show that Eva identified 1.85 times as many asymptomatic, infected travellers as random surveillance testing, with up to 2-4 times as many during peak travel, and 1.25-1.45 times as many asymptomatic, infected travellers as testing policies that utilize only epidemiological metrics. We demonstrate that this latter benefit arises, at least partially, because population-level epidemiological metrics had limited predictive value for the actual prevalence of SARS-CoV-2 among asymptomatic travellers and exhibited strong country-specific idiosyncrasies in the summer of 2020. Our results raise serious concerns on the effectiveness of country-agnostic internationally proposed border control policies3 that are based on population-level epidemiological metrics. Instead, our work represents a successful example of the potential of reinforcement learning and real-time data for safeguarding public health.

Impact and torsional behavior of additive layer-manufactured biopolymer: An advancement for orthopedic applications.

Distal ulna locking bone plates (DLBPs) are commonly employed in the treatment of distal ulna fractures. However, commercially available metallic bone plates experience stress shielding and lack corrosion resistance. Poly lactic acid (PLA) is highly favored biopolymer due to its biocompatible and bioabsorbable nature with human tissues. The use of additive layer manufacturing (ALM) is gaining attention for creating customized implants with intricate structures tailored to patient autonomy. ALM-based PLA bone plates must provide high resistance against impact and torsional forces, necessitating the adjustment of printing process parameters. This study focuses on examining the influence of key printing parameters, on the impact strength and torque-withstanding capability of DLBPs. Experimental results, along with microscopic images, reveal that an increase in infill density (IF) and wall thickness imparts strong resistance to layers against crack propagation under impact and torsional loads. On the contrary, an increase in layer height and printing speed leads to delamination and early fracture of layers during impact and torsional testing. IF significantly contributes to improving the impact strength and torque-withstanding capability of DLBPs by 70.53% and 80.65%, respectively. The study highlights the potential of the ALM technique in developing DLBPs with sufficient mechanical strength for biomedical applications.

Dose and fractionation regimen for brachytherapy boost in cervical cancer in the US.

PURPOSE: Curative-intent radiotherapy for locally advanced and select early stage cervical cancer in the US includes external beam radiotherapy (EBRT) with brachytherapy. Although there are guidelines for brachytherapy dose and fractionation regimens, there are limited data on practice patterns. This study aims to evaluate the contemporary utilization of cervical cancer brachytherapy in the US and its association with patient demographics and facility characteristics. METHODS: We retrospectively analyzed clinical covariates of cervical cancer patients diagnosed and treated in 2018-2020 with curative-intent radiotherapy from the 2020 National Cancer Database. Associations between patient and institutional factors with the number of brachytherapy fractions were identified with logistic regression. Factors with association (p < 0.10) were then included in a multivariable logistic regression model. All tests were two-sided with significance <0.05 unless specified otherwise. RESULTS: Among the eligible 2517 patients, 97.3% received HDR or LDR and is further analyzed. More patients received HDR than LDR brachytherapy (98.9% vs 1.1%) and intracavitary than interstitial brachytherapy (86.4% vs 13.6%). The most common number of HDR fractions prescribed were 5 (51.0%), 4 (32.9%), and 3 (8.6%). After adjusting for the other variables in the model, ethnicity, private insurance status, overall insurance status, and facility type were the only factors that were significantly associated with the number of brachytherapy factions (p < 0.0001, p = 0.028, p = 0.001, and p < 0.0001, respectively, n = 2184). CONCLUSIONS: In the US, various HDR brachytherapy regimens are utilized depending on patient and institutional factors. Future research may optimize cervical cancer brachytherapy by correlating specific dose and fractionation regimens with patient outcomes.

A Novel Method for Prediction of Raised Intracranial Pressure Through Automated ONSD and ETD Ratio Measurement From Ocular Ultrasound.

The paper presents a novel framework for the prediction of the raised Intracranial Pressure (ICP) from ocular ultrasound images of traumatic patients through automated measurement of Optic Nerve Sheath Diameter (ONSD) and Eyeball Transverse Diameter (ETD). The measurement of ONSD using an ocular ultrasound scan is non-invasive and correlates with the raised ICP. However, the existing studies suggested that the ONSD value alone is insufficient to indicate the ICP condition. Since the ONSD and ETD values may vary among patients belonging to different ethnicity/origins, there is a need for developing an independent global biomarker for predicting raised ICP condition. The proposed work develops an automated framework for the prediction of raised ICP by developing algorithms for the automated measurement of ONSD and ETD values. It is established that the ONSD and ETD ratio (OER) is a potential biomarker for ICP prediction independent of ethnicity and origin. The OER threshold value is determined by performing statistical analysis on the data of 57 trauma patients obtained from the AIIMS, New Delhi. The automated OER is computed and compared with the conventionally measured ICP by determining suitable correlation coefficients. It is found that there is a significant correlation of OER with ICP (r = .81, p ≤ .01), whereas the correlation of ONSD alone with ICP is relatively less (r = .69, p = .004). These correlation values indicate that OER is a better parameter for the prediction of ICP. Further, the threshold value of OER is found to be 0.21 for predicting raised ICP conditions in this study. Scatter plot and Heat map analysis of OER and corresponding ICP reveal that patients with OER ≥ 0.21, have ICP in the range of 17 to 35 mm Hg. In the data available for this research work, OER ranges from 0.17 to 0.35.

Association of pre-treatment lymphocyte-monocyte ratio with survival outcome in patients with head and neck cancer treated with chemoradiation.

BACKGROUND: Given the role of systematic inflammation in cancer progression, lymphocyte-monocyte ratio (LMR) from peripheral blood has been suggested as a biomarker to assess the extent of inflammation in several solid malignancies. However, the role of LMR as a prognostic factor in head and neck cancer was unclear in several meta-analyses, and there is a paucity of literature including patients in North America. We performed an observational cohort study to evaluate the association of LMR with survival outcomes in North American patients with head and neck cancer. METHODS: A single-institution, retrospective database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation from June 2007 to April 2021 at the Roswell Park Comprehensive Cancer Center. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The association of LMR with OS and CSS was examined using nonlinear Cox proportional hazard model using restricted cubic splines (RCS). Cox multivariable analysis (MVA) and Kaplan-Meier method were used to analyze OS and CSS. Pre-radiation LMR was then stratified into high and low based on its median value. Propensity scored matching was used to reduce the selection bias. RESULTS: A total of 476 patients met our criteria. Median follow up was 45.3 months (interquartile range 22.8-74.0). The nonlinear Cox regression model showed that low LMR was associated with worse OS and CSS in a continuous fashion without plateau for both OS and CSS. On Cox MVA, higher LMR as a continuous variable was associated with improved OS (adjusted hazard ratio [aHR] 0,90, 95% confidence interval [CI] 0.82-0.99, p = 0.03) and CSS (aHR 0.83, 95% CI 0.72-0.95, p = 0.009). The median value of LMR was 3.8. After propensity score matching, a total of 186 pairs were matched. Lower LMR than 3.8 remained to be associated with worse OS (HR 1.59, 95% CI 1.12-2.26, p = 0.009) and CSS (HR 1.68, 95% CI 1.08-2.63, p = 0.02). CONCLUSION: Low LMR, both as a continuous variable and dichotomized variable, was associated with worse OS and CSS. Further studies would be warranted to evaluate the role of such prognostic marker to tailor interventions.

Recent advancement in functional properties and toxicity assessment of plant-derived bioactive peptides using bioinformatic approaches.

Nowadays, biopeptides have gained considerable interest by the food industries, given their potent biological effect on health. BPs, when released from the sequence of their precursors by proteolytic enzymes, improved the various physiological functions of the body. Diabetic and hypertension are the two most common life-threatening diseases linked to dietary patterns. Angiotensin-converting enzyme (ACE) (hypertension-responsible glycoprotein) and dipeptidyl peptidase IV (DPP-IV) (proline-specific dimeric aminopeptidase) have been widely used as molecular target sites of action of bioactive compounds possessing antihypertensive and antidiabetic effects. Although, BPs possess considerable biological properties (antioxidant, antimicrobial, antiviral, immunomodulating, antiproliferative, antidiabetic, and antihypertensive effects), most of them possess inherent lacunae such as toxicity, allergenicity, bitterness, and lack of detailed mechanistic investigation, limiting their commercial application. The present review provides an overview on various sources of bioactive peptides, conventional and modern methods of extraction, and challenges that need to be addressed before its commercial application. In addition, bioinformatics' role in exploring the functional properties of biopeptides (ACE and DPP-IV inhibitory effects) toxicity, the target site of action with special reference to plant-based peptides, and recent burgeoning proficiencies in biopeptide research have been discussed.

Temperature dependent characteristics of flexible p-PANI/n-ZnO based hybrid heterojunction diode.

This study aims to develop and characterize a flexible p-PANI/n-ZnO heterojunction diode developed from a combination of electrochemical and sputtering technique. Investigation of structural properties and morphology of the thin films has been done from XRD and SEM analysis. To study the temperature effect on the electrical properties of the diode, current-voltage-temperature (I-V-T) measurements were done for the temperature range 25-300 K. Applying the ideal thermionic emission theory, various diode parameters like reverse saturation current, quality factor, series resistance and barrier height were computed utilizing the semilogarithmic plot ofI-Vcurve and Cheungs' method. Barrier height, reverse saturation current and quality factor calculated from ln(I)versusVcurve were observed to vary from 0.0627-0.725 eV, 0.236-98.8 nA and 54.43-3.29 respectively over the temperature range 25-300 K. It has been found that the series resistance falls with a rise in temperature. The barrier height, series resistance and ideality factor were observed to vary from 0.0628-0.692 eV, 15 900-46.8 Kohm and 41.88-2.27 respectively for the temperature range 25-300 K. The activation energy estimated from Arrhenius plot was observed to be 14.51 meV. Additionally, the fabricated PANI/ZnO diode was mechanically robust that can be bent without affecting its performance.

Insights of Endocytosis Signaling in Health and Disease.

Endocytosis in mammalian cells is a fundamental cellular machinery that regulates vital physiological processes, such as the absorption of metabolites, release of neurotransmitters, uptake of hormone cellular defense, and delivery of biomolecules across the plasma membrane. A remarkable characteristic of the endocytic machinery is the sequential assembly of the complex proteins at the plasma membrane, followed by internalization and fusion of various biomolecules to different cellular compartments. In all eukaryotic cells, functional characterization of endocytic pathways is based on dynamics of the protein complex and signal transduction modules. To coordinate the assembly and functions of the numerous parts of the endocytic machinery, the endocytic proteins interact significantly within and between the modules. Clathrin-dependent and -independent endocytosis, caveolar pathway, and receptor mediated endocytosis have been attributed to a greater variety of physiological and pathophysiological roles such as, autophagy, metabolism, cell division, apoptosis, cellular defense, and intestinal permeabilization. Notably, any defect or alteration in the endocytic machinery results in the development of pathological consequences associated with human diseases such as cancer, cardiovascular diseases, neurological diseases, and inflammatory diseases. In this review, an in-depth endeavor has been made to illustrate the process of endocytosis, and associated mechanisms describing pathological manifestation associated with dysregulated endocytosis machinery.

Identification of plastic rice in adulterated raw and cooked rice.

In the present study, attempts have been made to identify the presence of plastic rice in adulterated raw and cooked rice by comparing the compositional and morphological properties of fake rice and real rice using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA) techniques. Various rice samples from the national capital region of India were studied for their compositional and morphological properties. The surface morphology of real rice and plastic rice was analyzed using scanning electron microscopy. Results suggest that plastic rice used as an adulterant in raw or cooked rice is made up of polystyrene, which is a well-known toxic chemical entity. The studies suggest that these techniques can be used as a scientific tool to detect and identify the presence of plastic rice in adulterated raw and cooked rice.

Targeting lysophosphatidic acid receptor with Ki16425 impedes T cell lymphoma progression through apoptosis induction, glycolysis inhibition, and activation of antitumor immune response.

Lysophosphatidic acid (LPA) is a small phospholipid that acts as an extracellular lipid mediator. It promotes cancer progression by altering a wide array of cellular processes, including apoptosis, survival, angiogenesis, invasion, and migration through binding with its cognate receptors. Intriguingly, our previous study showed that in vitro treatment of LPA induced survival of T lymphoma cells. Hence, the present investigation was designed to investigate the antitumor potential of Ki16425, an antagonist of LPA receptors, against T cell lymphoma. Our in vitro results showed inhibition of LPA-mediated survival and metabolic activity of T lymphoma cells by Ki16425. Further, in vivo experimental findings indicated the tumor retarding potential of Ki16425 against T cell lymphoma through apoptosis induction, glycolysis inhibition, and immunoactivation. The administration of Ki16425 triggered apoptosis by down-regulating the expression of Bcl2 and up-regulating p53, Bax, cleaved caspase-3, and Cyt c expression. Further, Ki16425 suppressed glycolytic activity with concomitantly decreased expression of GLUT3 and MCT1. Moreover, we also noticed an elevated level of NO and iNOS in tumor cells after Ki16425 administration which might also be responsible for apoptosis induction and suppressed glycolysis. Additionally, we observed an increased population of total leukocytes, lymphocytes, and monocytes along with increased thymocytes count and IL-2 and IFN-γ levels. Besides, we observed amelioration of tumor-induced kidney and liver damages by Ki16425. Taken together, this is the first study that demonstrates that LPA receptors could be potential future therapeutic targets for designing promising therapeutic strategies against T cell lymphoma.

Phosphodiesterase 5 inhibitor sildenafil potentiates the antitumor activity of cisplatin by ROS-mediated apoptosis: a role of deregulated glucose metabolism.

Cyclic nucleotide phosphodiesterase 5 (PDE5) has been recently identified to play a crucial role in the progression of many cancers. PDE5 promotes tumorigenesis by dysregulating various cellular processes such as proliferation, apoptosis, angiogenesis, and invasion and migration. Interestingly, multiple studies have reported the promising chemosensitizing potential of PDE5 inhibitor sildenafil in breast, colon, prostate, glioma, and lung cancers. However, to date, the chemosensitizing action of sildenafil is not evaluated in T cell lymphoma, a rare and challenging neoplastic disorder. Hence, the present investigation was undertaken to examine the chemosensitizing potential of sildenafil against T cell lymphoma along with elucidation of possible involvement of altered apoptosis and glucose metabolism. The experimental findings of this study showed that sildenafil enhances the cytotoxic ability of cisplatin by apoptosis induction through altering the levels of apoptosis regulatory molecules: Bcl-2, Bax, cytochrome c (Cyt c), cleaved caspase-3, and poly (ADP-ribose) polymerase (PARP). These molecular alterations were possibly driven by sildenafil through reactive oxygen species (ROS). Sildenafil deregulates glucose metabolism by markedly lowering the expression of glycolysis regulatory molecules, namely glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), hexokinase II (HKII), pyruvate kinase M2 (PKM2), and pyruvate dehydrogenase kinase 1 (PDK1) via suppressing hypoxia-inducible factor 1-alpha (HIF-1α) expression. Hence, sildenafil potentiates the tumor cell killing ability of cisplatin by augmenting ROS production through switching the glucose metabolism from glycolysis to oxidative phosphorylation (OXPHOS). Overall, our study demonstrates that sildenafil might be a promising adjunct therapeutic candidate in designing novel combinatorial chemotherapeutic regimens against T cell lymphoma.

Acquired cutis laxa type II (Marshall syndrome) in a 3-month-old boy.

Acquired cutis laxa type II (Marshall syndrome) is a post-inflammatory elastolysis occurring in infancy and childhood. It is challenging to treat with very few effective treatment options available. Herein, we describe the case of a 3-month-old boy with acquired cutis laxa type II secondary to a neutrophilic dermatosis. Early treatment of the initial inflammatory phase is essential to reduce the permanent sequelae.

Gallbladder perforation: A single-center experience in north India and a step-up approach for management.

BACKGROUND: Spontaneous gallbladder perforation (GBP) is an uncommon diagnosis. This study presented the experience of managing spontaneous GBP over nine years at a large, tertiary care university hospital in north India and investigated the outcomes and treatment strategies. METHODS: A retrospective review of prospectively maintained digital database of consecutive patients was performed. All patients received medical and/or surgical treatment for spontaneous GBP in our department between January 2010 and June 2018. RESULTS: We identified 151 patients (81 females and 70 males) with mean age of 53 years. Most common presenting features were pain (96.7%), fever (54.3%) and jaundice (31.1%). Most common cause was gallbladder stones (84.8%) followed by common bile duct stones (30.5%), xanthogranulomatous cholecystitis (17.9%) and malignancy (11.9%). As per Niemeier classification, 8.6% had type 1 GBP (free perforation in peritoneal cavity), 76.2% had type 2 GBP (localized perforation) and 13.2% had type 3 GBP (cholecysto-enteric fistula). About 60% of the perforations were diagnosed preoperatively. Type 1 was more common in patients with diabetes and also had the worst prognosis. Surgery was performed in 109 patients (72.2%). Seven patients (4.6%) had a postoperative morbidity of Clavien-Dindo III or higher. There were three mortalities in patients who underwent surgery. CONCLUSIONS: High index of suspicion is required for preoperative diagnosis of GBP, especially in types 2 and 3. Laparoscopic cholecystectomy can be difficult in these patients and patients may require open or partial cholecystectomy. Early diagnosis and step-up approach for the treatment of GBP is critical.

Personal financial literacy among Indian postgraduate residents.

Background Postgraduate residents' ability to understand and effectively manage their finances is variable. We conducted this study to assess the awareness of personal financial literacy among Indian residents. Methods We circulated a web-based cross-sectional Google Forms multiple-choice questionnaire having questions in three categories including financial awareness, current financial status and plans among 400 Indian residents. Results A total of 215 Indian residents (53.75%) responded to the survey (men 80.9%, unmarried 74.4% and pursuing broad specialties 83.3%). The majority were unaware of stocks, special student/doctor loans, tax planning, life insurance, professional indemnity and tax/financial planning. The majority opined that personal finance and investing should be taught at medical school/residency. A financial pyramid based on the hierarchy of needs is proposed. Conclusion Lack of financial literacy and planning was seen among the majority of Indian residents. Our study highlights this gap in the medical curriculum and the need for formal structured financial education during training.

Extra-pulmonary Manifestations of COVID-19 in Western India.

SARS-CoV-2 is well known disorder to affect respiratory system, although it can also influence several extrapulmonary organs through variety of pathological mechanism. In this study, we aimed to discuss the prevalence of atypical and/or extrapulmonary manifestations in COVID-19, therefor action for early isolation and diagnosis can be initiated to prevent spread of infection. METHODS: This retrospective observational study included 4200 admitted COVID-19 patients. The patient's data concerning medical history, clinical symptoms at presentation and during course of hospitalization, laboratory and radiological diagnosis and underlying chronic medical illness were extracted from their medical records. Data of extrapulmonary and/or atypical presentations of COVID-19 were compiled and tabulated to know prevalence of these manifestations. RESULTS: In this study, 1260 patients (30%) had symptomatic presentation. Major extrapulmonary clinical manifestation includes fatigue in 72.22% patients, impaired sense of taste (ageusia) in 58.73%, loss of appetite in 52.78%, impaired sense of smell (anosmia) in 46.83%, palpitation in 33.33%, headache in 33.17%, nausea/vomiting in 31.43%, diarrhoea in 25.40% patients. Among symptomatic COVID-19 patients, 95.56% patients had sinus tachycardia, 38.49% had lymphocytopenia, 36.83% had hepatitis, 35.48% had leukopenia, 27.83% had gastroenteritis, 22.22% had sepsis, 20.87% had proteinuria, 17.30% had coronary artery disease and 16.34% had acute kidney injury in decreasing order. Prevalence of coagulation defect associated disorder were found to be deep venous thrombosis in 15.56% patients, acute coronary syndrome in 7.78%, brain infarct in 6.35%, pulmonary artery thrombosis in 3.25% and SMA thrombosis in 0.32% of symptomatic patients. CONCLUSION: Patients of SARS-CoV-2 had widespread organ-specific manifestations with involvement of almost all organ system of body. Clinicians must have knowledge of these extrapulmonary symptoms or atypical presentation of COVID-19 as it assists in early diagnosis, isolation of suspected patients and limit the transmission of infection in the hospital settings.

Predictors of Outcome in Acute Respiratory Distress Syndrome in Acute Febrile Illness in Medical Intensive Care Unit.

AIMS: Acute Respiratory Distress Syndrome (ARDS) is a known complication of acute febrile illness (AFI). The in-hospital mortality rate of ARDS is between 35-44%. Our study aimed to identify the different parameters that could be used to detect patients at higher risk of poor outcome in AFI complicated by ARDS. METHODS: 130 patients with AFI complicated by ARDS as per Berlin definition, admitted at the Medical Intensive Care Unit of Seth GS Medical College KEM Hospital Mumbai, were studied over a period of 18 months. Investigations done during the course of MICU stay were noted. From the reports, SOFA score, delta SOFA score, Lung Injury Score (LIS), Disseminated Intravascular Coagulation (DIC) score (by ISTH scoring system) were also calculated. Main outcome was recorded as transfer out from the MICU or death. RESULTS: Etiology of the 130 patients of AFI with ARDS was as follows-dengue 32 patients (24.6%), H1N1 -31(23.8%), undifferentiated fever -30 (23.1%), leptospirosis-22 (16.9%), malaria-15 (11.5%). Our study had a mortality rate of 25.4 %( n=33). 40.8% of the study population required invasive ventilation at admission. SOFA score at admission and 48 hours, delta SOFA score, PaO2/ FiO2 ratio at admission and 48 hours, Blood Urea Nitrogen (BUN), creatinine, bicarbonate and albumin were the significant predictors of overall outcome. Hemoglobin, platelets and leukocyte counts, pH, pO2 , pCO2 at admission and 48 hours, Lung Injury Score (LIS) and DIC score were not significant predictors of outcome. CONCLUSION: SOFA score at admission and 48 hours, delta SOFA score and PaO2 / FiO2 ratio were significant predictors of outcome in patients of acute febrile illness with ARDS. LIS and DIC score were not significant predictors of outcome.

Establishment of SMS Dengue Severity Score.

BACKGROUND: Dengue infection is a disease that progresses rapidly to life-threatening conditions. Our goal was to develop a practical scoring system based on clinical profiles and routine tests to predict the severity of infection. METHODS: This cross-sectional observational study included 500 patients with dengue infection. Patient demographics, clinical symptoms, regular laboratory tests, and results were collected. Dengue infections are divided into three classes, depending on their severity: dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). Based on the total score, patients were divided into three severities. RESULTS: Patients with DSS and DHF scored higher with worsening clinical features and routine laboratory tests compared to DF. Clinical predictors of severity include older age, increased white blood cell (WBC) count, increased hematocrit, increased prothrombin time, decreased platelet count, decreased blood pressure, presence of peri-gallbladder (GB) edema, third space loss, hepatomegaly, and other organ involvement. The severity range is 0-12, and the score is 0-3 for DF, 4-8 for DHF, and 9-12 for DSS. Based on the derived scores, patients were classified according to their original severity in 63% of cases. CONCLUSION: This dengue infection severity scores correctly classified patients according to their original severity grade of DF, DHF, or DSS. This scoring system helps to quickly assess dengue infections and start treatment according to the correct severity category.

Venture creation in the aftermath of COVID-19: The impact of US governor party affiliation and discretion.

In the USA, governors became central figures in the fight against the novel coronavirus. In many cases, state leaders were forced to choose between preserving life and protecting economic livelihood. While prior research has underscored the important role that US governors played in implementing healthcare policies at the onset of the COVID-19 pandemic, we know little about how characteristics of state leaders impacted self-employment. In this paper, we draw from upper echelons theory to examine how governor party and discretion impacted venture creation in the food and restaurant industry. Interestingly, we find no significant relationship between governor party and venture creation. However, we find that when the governor and legislature were unified in their political party - irrespective of party line - there were a higher number of new food and restaurant ventures created. We also found this effect to be strengthened when small business unemployment levels were higher. We explore the implications of these results for how unity of command may be beneficial during times of crisis.

De-Escalated Adjuvant Therapy After Transoral Robotic Surgery for Human Papillomavirus-Related Oropharyngeal Carcinoma: The Sinai Robotic Surgery (SIRS) Trial.

BACKGROUND: Treatment of human papillomavirus-related oropharyngeal squamous cell carcinoma (HPVOPC) results in unprecedented high survival rates but possibly unnecessary toxicity. We hypothesized that upfront surgery and neck dissection followed by reduced-dose adjuvant therapy for early and intermediate HPVOPC would ultimately result in equivalent progression-free survival (PFS) and overall survival while reducing toxicity. METHODS: This study was a nonrandomized phase II trial for early-stage HPVOPC treated with transoral robotic surgery (TORS) followed by reduced-dose radiotherapy. Patients with previously untreated p16-positive HPVOPC and <20 pack years' smoking history were enrolled. After robotic surgery, patients were assigned to group 1 (no poor risk features; surveillance), group 2 (intermediate pathologic risk factors [perineural invasion, lymphovascular invasion]; 50-Gy radiotherapy), or group 3 (poor prognostic pathologic factors [extranodal extension [ENE], more than three positive lymph nodes and positive margin]; concurrent 56-Gy chemoradiotherapy with weekly cisplatin). RESULTS: Fifty-four patients were evaluable; there were 25 in group 1, 15 in group 2, and 14 in group 3. Median follow-up was 43.9 months (9.6-75.8). Disease-specific survival was 98.1%, and PFS was 90.7%. PFS probability via Kaplan-Meier was 91.3% for group 1, 86.7% for group 2, and 93.3% for group 3. There were five locoregional failures (LRFs), including one distant metastasis and one contralateral second primary. Average time to LRF was 18.9 months (9.6-59.0); four LRFs were successfully salvaged, and the patients remain disease free (11.0-42.7 months); one subject remains alive with disease. CONCLUSION: The results indicate that upfront surgery with neck dissection with reduced-dose radiation for T1-2, N1 stage (by the eighth edition American Joint Committee on Cancer staging manual) HPVOPC results in favorable survival with excellent function in this population. These results support radiation dose reduction after TORS as a de-escalation strategy in HPVOPC. IMPLICATIONS FOR PRACTICE: Transoral robotic surgery can provide a safe platform for de-escalation in carefully selected patients with early-stage human papillomavirus-related oropharyngeal cancer. In this clinical trial, disease-specific survival was 100%, over 90% of the cohort had a reduction of therapy from standard of care with excellent functional results, and the five patients with observed locoregional failures were successfully salvaged.