Neel Shah - Academia.edu (original) (raw)

Papers by Neel Shah

Maternal and Child Health Journal

Introduction In the US, there are striking inequities in maternal health outcomes between racial ... more Introduction In the US, there are striking inequities in maternal health outcomes between racial and ethnic groups. Community-based organizations (CBOs) provide social support services that are critical in addressing the needs of clients of color during and after pregnancy. Methods We conducted a descriptive, cross-sectional mixed methods study of CBOs in Greater Boston that provide social support services to pregnant and postpartum clients. In May-August 2020, we administered an online survey about organizational characteristics, client population, and services offered. In July-August 2020, we conducted semi-structured interviews focused on services provided, gaps in services, and the impact of structural racism on clients. We used descriptive statistics to characterize CBOs and services and used thematic analysis to extract themes from the qualitative data. Results A total of 21 unique CBOs participated with 17 CBOs completing the survey and 14 participating in interviews. CBOs served between 10 and 35,000 pregnant and postpartum clients per year (median = 200), and about half (n = 8) focused their programming on pregnant and postpartum clients. The most significant gaps in social support services were housing and childcare. Respondents identified racism and lack of coordination among organizations as the two primary barriers to accessing social support. Discussion CBOs face multiple challenges to providing social support to pregnant and postpartum clients of color, and significant gaps exist in the types of services currently provided. Improved coordination among CBOs and advocacy efforts to develop community-informed solutions are needed to reduce barriers to social support.

Proceedings of the 19th International Middleware Conference, 2018

Cloud applications are appealing targets to attackers, yet current cloud infrastructures have few... more Cloud applications are appealing targets to attackers, yet current cloud infrastructures have few ways of helping defend their customers from attacks. However, the use of virtual machines, and the economy of scale found in cloud platforms, provides an opportunity to offer strong security guarantees to tenants at low cost to the cloud provider. We present CRIMES, an evidence based, modular security framework for cloud platforms that uses speculative execution coupled with memory introspection tools to detect malicious behavior in real time. By buffering VM outputs (i.e., outgoing network packets and disk writes) until a scan has been completed, CRIMES gives strong guarantees about the amount of damage an attack can do, while minimizing overheads. When an attack is detected, CRIMES rolls back to a recent checkpoint and performs automated forensic analysis to help pinpoint the source of an attack. Our evaluation demonstrates that CRIMES incurs less overhead compared to memory protectio...

Journal of Evolution of medical and Dental Sciences, 2015

SSRN Electronic Journal, 2019

Using 14 major commodity (bullion, base metal, agricultural and energy) futures contracts of Mult... more Using 14 major commodity (bullion, base metal, agricultural and energy) futures contracts of Multi Commodity Exchange (MCX) from July 2009 to December 2018, we examine the effects of margin changes on commodity futures markets in India. Our empirical results indicate that all commodity futures except Aluminium, Copper and Brent Crude, net margin is maximum for the quartile closet to the maturity. Similarly, volatility of margin imposition is the highest for the quartile closet to maturity. The increasing margin has a negative effect for all non-agricultural futures contracts except Aluminium and Brent Crude. The impact of a margin decrease on volume is weaker compared to a margin increase except for Natural Gas and Crude Oil which show that volume increased on days when margin reduced. On the other hand, both increase and decrease in margins have negative impact on open interest in all the commodity futures contracts.

eLife, 2019

Predicting ancestral sequences of protein kinases reveals the molecular details that underlie dif... more Predicting ancestral sequences of protein kinases reveals the molecular details that underlie different modes of activation.

Obstetrics & Gynecology, 2018

OBJECTIVE To demonstrate the association between increases in labor and delivery unit census and ... more OBJECTIVE To demonstrate the association between increases in labor and delivery unit census and delays in patient care decisions using a computer simulation module. METHODS This was an observational cohort study of labor and delivery unit nurse managers. We developed a computer module that simulates the physical layout and clinical activity of the labor and delivery unit at our tertiary care academic medical center, in which players act as clinical managers in dynamically allocating nursing staff and beds as patients arrive, progress in labor, and undergo procedures. We exposed nurse managers to variation in patient census and measured the delays in resource decisions over the course of a simulated shift. We used mixed logistic and linear regression models to analyze the associations between patient census and delays in patient care. RESULTS Thirteen nurse managers participated in the study and completed 17 12-hour shifts, or 204 simulated hours of decision-making. All participants reported the simulation module reflected their real-life experiences at least somewhat well. We observed 1.47-increased odds (95% CI 1.18-1.82) of recommending a patient ambulate in early labor for every additional patient on the labor and delivery unit. For every additional patient on the labor and delivery unit, there was a 15.9-minute delay between delivery and transfer to the postpartum unit (95% CI 2.4-29.3). For every additional patient in the waiting room, we observed a 33.3-minute delay in the time patients spent in the waiting room (95% CI 23.2-43.5) and a 14.3-minute delay in moving a patient in need of a cesarean delivery to the operating room (95% CI 2.8-25.8). CONCLUSION Increasing labor and delivery unit census is associated with patient care delays in a computer simulation. Computer simulation is a feasible and valid method of demonstrating the sensitivity of care decisions to shifts in patient volume.

JAMA internal medicine, 2018

Proceedings of the National Academy of Sciences, 2017

The protein trans-splicing (PTS) activity of naturally split inteins has found widespread use in ... more The protein trans-splicing (PTS) activity of naturally split inteins has found widespread use in chemical biology and biotechnology. However, currently used naturally split inteins suffer from an “extein dependence,” whereby residues surrounding the splice junction strongly affect splicing efficiency, limiting the general applicability of many PTS-based methods. To address this, we describe a mechanism-guided protein engineering approach that imbues ultrafast DnaE split inteins with minimal extein dependence. The resulting “promiscuous” inteins are shown to be superior reagents for protein cyclization and protein semisynthesis, with the latter illustrated through the modification of native cellular chromatin. The promiscuous inteins reported here thus improve the applicability of existing PTS methods and should enable future efforts to engineer promiscuity into other naturally split inteins.

Surgery, Sep 1, 2017

Health care costs are an important policy focus in the United States. The magnitude and drivers o... more Health care costs are an important policy focus in the United States. The magnitude and drivers of variation in the costs of common operative procedures are not well understood. We sought to characterize variation in costs across hospitals. We used data from the Nationwide Inpatient Sample from 2001-2011 for 5 elective operations: colectomy, coronary artery bypass graft, total knee arthroplasty, cesarean section, and lung resection. Hospitals were benchmarked for each using hierarchical risk- and reliability-adjustment methods to generate an observed-to-expected cost ratio, which was adjusted for patient demographics, comorbidity, wage index, and procedure complexity. Hospitals were divided into quintiles. Characteristics of high- and low-quintile hospitals and their adjusted outcomes were examined. Cost observed-to-expected ratios ranged widely for all 5 procedures: 14.9-fold for colectomy, 5.5-fold for coronary artery bypass graft, 12.5-fold for lung resection, 10.6-fold for total...

Nature, Jun 29, 2017

Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens t... more Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens to drive expression of the normally silent E26 transformation-specific (ETS) transcription factor ERG in prostate cells. Recent genomic landscape studies of such cancers have reported recurrent point mutations and focal deletions of another ETS member, the ETS2 repressor factor ERF. Here we show these ERF mutations cause decreased protein stability and mostly occur in tumours without ERG upregulation. ERF loss recapitulates the morphological and phenotypic features of ERG gain in normal mouse prostate cells, including expansion of the androgen receptor transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of Pten loss that yields oncogenic activity by ERG. In the more common scenario of ERG upregulation, chromatin immunoprecipitation followed by sequencing indicates that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites both in ...

The American Journal of Medicine, 2017

eLife, 2016

The sequence of events that initiates T cell signaling is dictated by the specificities and order... more The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues. This mechanism prevents ZAP-70 from phosphorylating its own activation loop, thereby enforcing its strict dependence on Lck for activation. The sequence features in ZAP-70, LAT, and SLP-76 that underlie electrostatic selectivity likely contribute to the specific response...

British Journal of Medicine and Medical Research, 2016

2016 IEEE Applied Power Electronics Conference and Exposition (APEC), 2016

Obstetrics and Gynecology International, 2011

Objectives. We assess whether it is feasible for robotic hysterectomy for endometrial cancer to b... more Objectives. We assess whether it is feasible for robotic hysterectomy for endometrial cancer to be less expensive to society than traditional laparoscopic hysterectomy or abdominal hysterectomy.Methods. We performed a retrospective cohort analysis of patient characteristics, operative times, complications, and hospital charges from all () endometrial cancer patients who underwent hysterectomy in 2009 at our hospital. Per patient costs of each hysterectomy method were examined from the societal perspective. Sensitivity analysis and Monte Carlo simulation were performed using a cost-minimization model.Results. 40 (17.1%) of hysterectomies for endometrial cancer were robotic, 91 (38.9%), were abdominal, and 103 (44.0%) were laparoscopic. 96.3% of the variation in operative cost between patients was predicted by operative time (, ). Mean operative time for robotic hysterectomy was significantly longer than other methods (). Abdominal hysterectomy was consistently the most expensive whil...

Journal of Clinical Oncology, 2005

Purpose The use of gefitinib, the first drug approved to inhibit the epidermal growth factor rece... more Purpose The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non–small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non–small-cell lung cancer. Methods This article reviews gefitinib’s indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. Results We present our recommendations for the management of rash and diarrhea caused by this agent. Conclusion This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.

Journal of Cancer Survivorship, 2011

Breast cancer is the leading cause of cancer, and the second leading cause of cancer death in wom... more Breast cancer is the leading cause of cancer, and the second leading cause of cancer death in women. Due to advances in medicine, the 10 year survival rate is 80%, resulting in a large and growing number of breast cancer survivors. Definitions of cancer survivorship from a number of professional organizations and researchers vary, but the research is scant on the meaning of cancer survivorship to people with and without a prior cancer history. Two studies were conducted (1) to compare individuals with and without a prior personal cancer diagnosis in terms of those who identified as survivors vs. those who did not identify as survivors and (2) to explore explanations of those with and without a prior personal cancer for the term cancer survivor. In Study 1, individuals were surveyed at cancer-themed community health fairs. In Study 2, women were surveyed at a breast oncology clinic. In Study 1 comparing those with and without a prior cancer diagnosis, prior cancer history was the best predictor of survivorship identity, and only three individuals without a prior cancer history included family and friends as survivors. In Study 2 of those with a personal history, longer time since diagnosis, type of cancer (ductal), and comparative risk (higher) were associated with survivor identity. Completion of treatment was seen as a 'rite of passage', and thus, may be seen as a shift from the patient identity, which may have negative connotations, to the positive identity of survivor. Definitions of survivorship vary considerably, and caution should be used when applying the term to those who have no prior personal cancer diagnosis and to those who have had a more recent cancer diagnosis with a more severe disease course.

Maternal and Child Health Journal

Introduction In the US, there are striking inequities in maternal health outcomes between racial ... more Introduction In the US, there are striking inequities in maternal health outcomes between racial and ethnic groups. Community-based organizations (CBOs) provide social support services that are critical in addressing the needs of clients of color during and after pregnancy. Methods We conducted a descriptive, cross-sectional mixed methods study of CBOs in Greater Boston that provide social support services to pregnant and postpartum clients. In May-August 2020, we administered an online survey about organizational characteristics, client population, and services offered. In July-August 2020, we conducted semi-structured interviews focused on services provided, gaps in services, and the impact of structural racism on clients. We used descriptive statistics to characterize CBOs and services and used thematic analysis to extract themes from the qualitative data. Results A total of 21 unique CBOs participated with 17 CBOs completing the survey and 14 participating in interviews. CBOs served between 10 and 35,000 pregnant and postpartum clients per year (median = 200), and about half (n = 8) focused their programming on pregnant and postpartum clients. The most significant gaps in social support services were housing and childcare. Respondents identified racism and lack of coordination among organizations as the two primary barriers to accessing social support. Discussion CBOs face multiple challenges to providing social support to pregnant and postpartum clients of color, and significant gaps exist in the types of services currently provided. Improved coordination among CBOs and advocacy efforts to develop community-informed solutions are needed to reduce barriers to social support.

Proceedings of the 19th International Middleware Conference, 2018

Cloud applications are appealing targets to attackers, yet current cloud infrastructures have few... more Cloud applications are appealing targets to attackers, yet current cloud infrastructures have few ways of helping defend their customers from attacks. However, the use of virtual machines, and the economy of scale found in cloud platforms, provides an opportunity to offer strong security guarantees to tenants at low cost to the cloud provider. We present CRIMES, an evidence based, modular security framework for cloud platforms that uses speculative execution coupled with memory introspection tools to detect malicious behavior in real time. By buffering VM outputs (i.e., outgoing network packets and disk writes) until a scan has been completed, CRIMES gives strong guarantees about the amount of damage an attack can do, while minimizing overheads. When an attack is detected, CRIMES rolls back to a recent checkpoint and performs automated forensic analysis to help pinpoint the source of an attack. Our evaluation demonstrates that CRIMES incurs less overhead compared to memory protectio...

Journal of Evolution of medical and Dental Sciences, 2015

SSRN Electronic Journal, 2019

Using 14 major commodity (bullion, base metal, agricultural and energy) futures contracts of Mult... more Using 14 major commodity (bullion, base metal, agricultural and energy) futures contracts of Multi Commodity Exchange (MCX) from July 2009 to December 2018, we examine the effects of margin changes on commodity futures markets in India. Our empirical results indicate that all commodity futures except Aluminium, Copper and Brent Crude, net margin is maximum for the quartile closet to the maturity. Similarly, volatility of margin imposition is the highest for the quartile closet to maturity. The increasing margin has a negative effect for all non-agricultural futures contracts except Aluminium and Brent Crude. The impact of a margin decrease on volume is weaker compared to a margin increase except for Natural Gas and Crude Oil which show that volume increased on days when margin reduced. On the other hand, both increase and decrease in margins have negative impact on open interest in all the commodity futures contracts.

eLife, 2019

Predicting ancestral sequences of protein kinases reveals the molecular details that underlie dif... more Predicting ancestral sequences of protein kinases reveals the molecular details that underlie different modes of activation.

Obstetrics & Gynecology, 2018

OBJECTIVE To demonstrate the association between increases in labor and delivery unit census and ... more OBJECTIVE To demonstrate the association between increases in labor and delivery unit census and delays in patient care decisions using a computer simulation module. METHODS This was an observational cohort study of labor and delivery unit nurse managers. We developed a computer module that simulates the physical layout and clinical activity of the labor and delivery unit at our tertiary care academic medical center, in which players act as clinical managers in dynamically allocating nursing staff and beds as patients arrive, progress in labor, and undergo procedures. We exposed nurse managers to variation in patient census and measured the delays in resource decisions over the course of a simulated shift. We used mixed logistic and linear regression models to analyze the associations between patient census and delays in patient care. RESULTS Thirteen nurse managers participated in the study and completed 17 12-hour shifts, or 204 simulated hours of decision-making. All participants reported the simulation module reflected their real-life experiences at least somewhat well. We observed 1.47-increased odds (95% CI 1.18-1.82) of recommending a patient ambulate in early labor for every additional patient on the labor and delivery unit. For every additional patient on the labor and delivery unit, there was a 15.9-minute delay between delivery and transfer to the postpartum unit (95% CI 2.4-29.3). For every additional patient in the waiting room, we observed a 33.3-minute delay in the time patients spent in the waiting room (95% CI 23.2-43.5) and a 14.3-minute delay in moving a patient in need of a cesarean delivery to the operating room (95% CI 2.8-25.8). CONCLUSION Increasing labor and delivery unit census is associated with patient care delays in a computer simulation. Computer simulation is a feasible and valid method of demonstrating the sensitivity of care decisions to shifts in patient volume.

JAMA internal medicine, 2018

Proceedings of the National Academy of Sciences, 2017

The protein trans-splicing (PTS) activity of naturally split inteins has found widespread use in ... more The protein trans-splicing (PTS) activity of naturally split inteins has found widespread use in chemical biology and biotechnology. However, currently used naturally split inteins suffer from an “extein dependence,” whereby residues surrounding the splice junction strongly affect splicing efficiency, limiting the general applicability of many PTS-based methods. To address this, we describe a mechanism-guided protein engineering approach that imbues ultrafast DnaE split inteins with minimal extein dependence. The resulting “promiscuous” inteins are shown to be superior reagents for protein cyclization and protein semisynthesis, with the latter illustrated through the modification of native cellular chromatin. The promiscuous inteins reported here thus improve the applicability of existing PTS methods and should enable future efforts to engineer promiscuity into other naturally split inteins.

Surgery, Sep 1, 2017

Health care costs are an important policy focus in the United States. The magnitude and drivers o... more Health care costs are an important policy focus in the United States. The magnitude and drivers of variation in the costs of common operative procedures are not well understood. We sought to characterize variation in costs across hospitals. We used data from the Nationwide Inpatient Sample from 2001-2011 for 5 elective operations: colectomy, coronary artery bypass graft, total knee arthroplasty, cesarean section, and lung resection. Hospitals were benchmarked for each using hierarchical risk- and reliability-adjustment methods to generate an observed-to-expected cost ratio, which was adjusted for patient demographics, comorbidity, wage index, and procedure complexity. Hospitals were divided into quintiles. Characteristics of high- and low-quintile hospitals and their adjusted outcomes were examined. Cost observed-to-expected ratios ranged widely for all 5 procedures: 14.9-fold for colectomy, 5.5-fold for coronary artery bypass graft, 12.5-fold for lung resection, 10.6-fold for total...

Nature, Jun 29, 2017

Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens t... more Half of all prostate cancers are caused by the TMPRSS2-ERG gene-fusion, which enables androgens to drive expression of the normally silent E26 transformation-specific (ETS) transcription factor ERG in prostate cells. Recent genomic landscape studies of such cancers have reported recurrent point mutations and focal deletions of another ETS member, the ETS2 repressor factor ERF. Here we show these ERF mutations cause decreased protein stability and mostly occur in tumours without ERG upregulation. ERF loss recapitulates the morphological and phenotypic features of ERG gain in normal mouse prostate cells, including expansion of the androgen receptor transcriptional repertoire, and ERF has tumour suppressor activity in the same genetic background of Pten loss that yields oncogenic activity by ERG. In the more common scenario of ERG upregulation, chromatin immunoprecipitation followed by sequencing indicates that ERG inhibits the ability of ERF to bind DNA at consensus ETS sites both in ...

The American Journal of Medicine, 2017

eLife, 2016

The sequence of events that initiates T cell signaling is dictated by the specificities and order... more The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues. This mechanism prevents ZAP-70 from phosphorylating its own activation loop, thereby enforcing its strict dependence on Lck for activation. The sequence features in ZAP-70, LAT, and SLP-76 that underlie electrostatic selectivity likely contribute to the specific response...

British Journal of Medicine and Medical Research, 2016

2016 IEEE Applied Power Electronics Conference and Exposition (APEC), 2016

Obstetrics and Gynecology International, 2011

Objectives. We assess whether it is feasible for robotic hysterectomy for endometrial cancer to b... more Objectives. We assess whether it is feasible for robotic hysterectomy for endometrial cancer to be less expensive to society than traditional laparoscopic hysterectomy or abdominal hysterectomy.Methods. We performed a retrospective cohort analysis of patient characteristics, operative times, complications, and hospital charges from all () endometrial cancer patients who underwent hysterectomy in 2009 at our hospital. Per patient costs of each hysterectomy method were examined from the societal perspective. Sensitivity analysis and Monte Carlo simulation were performed using a cost-minimization model.Results. 40 (17.1%) of hysterectomies for endometrial cancer were robotic, 91 (38.9%), were abdominal, and 103 (44.0%) were laparoscopic. 96.3% of the variation in operative cost between patients was predicted by operative time (, ). Mean operative time for robotic hysterectomy was significantly longer than other methods (). Abdominal hysterectomy was consistently the most expensive whil...

Journal of Clinical Oncology, 2005

Purpose The use of gefitinib, the first drug approved to inhibit the epidermal growth factor rece... more Purpose The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non–small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non–small-cell lung cancer. Methods This article reviews gefitinib’s indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. Results We present our recommendations for the management of rash and diarrhea caused by this agent. Conclusion This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib.

Journal of Cancer Survivorship, 2011

Breast cancer is the leading cause of cancer, and the second leading cause of cancer death in wom... more Breast cancer is the leading cause of cancer, and the second leading cause of cancer death in women. Due to advances in medicine, the 10 year survival rate is 80%, resulting in a large and growing number of breast cancer survivors. Definitions of cancer survivorship from a number of professional organizations and researchers vary, but the research is scant on the meaning of cancer survivorship to people with and without a prior cancer history. Two studies were conducted (1) to compare individuals with and without a prior personal cancer diagnosis in terms of those who identified as survivors vs. those who did not identify as survivors and (2) to explore explanations of those with and without a prior personal cancer for the term cancer survivor. In Study 1, individuals were surveyed at cancer-themed community health fairs. In Study 2, women were surveyed at a breast oncology clinic. In Study 1 comparing those with and without a prior cancer diagnosis, prior cancer history was the best predictor of survivorship identity, and only three individuals without a prior cancer history included family and friends as survivors. In Study 2 of those with a personal history, longer time since diagnosis, type of cancer (ductal), and comparative risk (higher) were associated with survivor identity. Completion of treatment was seen as a 'rite of passage', and thus, may be seen as a shift from the patient identity, which may have negative connotations, to the positive identity of survivor. Definitions of survivorship vary considerably, and caution should be used when applying the term to those who have no prior personal cancer diagnosis and to those who have had a more recent cancer diagnosis with a more severe disease course.