This paper studies the expansion of US child support policies from 1977 to 1992 and its consequences for marriage and fertility decisions. I develop a model showing that child support enforces ex ...ante commitment from men to provide financial support in the event of a child, which (1) increases premarital sex among couples unlikely to marry and (2) reduces the abortion rate by reducing the cost of child-rearing to single moms. Using variation in the rollout relative to the timing of nonmarital pregnancy, I find that child support policies reduced the likelihood of marriage and reduced the abortion rate.
While the social costs of gun violence are high, opponents of gun restrictions argue that gun ownership deters crime and creates a positive externality by increasing unobserved risk to criminals. ...This paper investigates the evidence for these two deterrence channels, exploiting the sudden disclosure of all handgun permit holders' names and addresses in two New York counties. Permit holders have more crime incidents at their homes relative to non-permit holders in the baseline, which is not driven by selection into neighborhoods. I find little evidence in favor of direct deterrence, and little evidence of peer deterrence. Instead, I find that victimization is associated with a higher likelihood of future gun ownership.
•Permit holders have more crime incidents at their homes relative to non-permit holders who live on the same street.•Disclosing permit holders’ names and addresses does not have a detectible effect on crime.•Revealing a higher density of permit holders around an address does not have a detectible effect on crime.•Victimization is associated with a higher likelihood of future gun ownership.
•There is heterogeneity in the management of bleeding during platelet transfusion refractoriness (PTR).•Antifibrinolytics are more commonly used in patients who suffered severe bleeding.•Grade A and ...B1U HLA-matched platelets are not always readily available.•The HLA typing and HLA antibody screen/identification testing are not always performed prior to PTR.•There is a significant morbidity impact on clinical outcomes due to PTR and its bleeding related complications.
Platelet transfusion refractoriness (PTR) secondary to human leukocyte antigen (HLA) alloimmunization is a challenge in the treatment of hematology-oncologypatients and increases the risk of morbidity and mortality from bleeding events. Guidelines for treating PTR have not been clearly described in literature. We aim to describe the practice patterns for the management of PTR secondary to HLA alloimmunization, and to assess the mortality, thrombosis and bleeding-related clinical outcomes at 30 days from diagnosis.
A retrospective review of 51 cases of PTR secondary to HLA alloimmunization were analyzed.
The majority of patients (98 %) had a diagnosis of hematological malignancy of which 88.2 % were undergoing active chemotherapy. Clinically relevant bleeding, by ISTH criteria, was observed in 33.3 %; hemorrhagic shock was diagnosed in 7%. The rate of bleeding-related mortality was estimated at 7.8 %. The use of antifibrinolytics and plasma products (including intravenous immunoglobulin) was more common in cases with major versus non-major bleeding. Grade A or B1U HLA matched products were available in less than half of cases.
There is heterogeneity in the management of the bleeding risk and bleeding events during PTR, with antifibrinolytics more commonly used in patients who suffered severe bleeding. Grade A and B1U HLA-matched platelets are not always readily available, and HLA-typing and HLA-antibody testing are not always performed prior to PTR. Prospective randomized control trials may help to determine the safety and efficacy of antifibrinolytics and other supportive measures in the management of PTR.
The Evolution of Work in the United States Atalay, Enghin; Phongthiengtham, Phai; Sotelo, Sebastian ...
American economic journal. Applied economics,
04/2020, Letnik:
12, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Using the text from job ads, we introduce a new dataset to describe the evolution of work from 1950 to 2000. We show that the transformation of the US labor market away from routine cognitive and ...manual tasks and toward nonroutine interactive and analytic tasks has been larger than prior research has found, with a substantial fraction of total changes occurring within narrowly defined job titles. We provide narrative and systematic evidence on changes in task content within job titles and on the emergence and disappearance of individual job titles.
New technologies and the labor market Atalay, Enghin; Phongthiengtham, Phai; Sotelo, Sebastian ...
Journal of monetary economics,
08/2018, Letnik:
97
Journal Article
Recenzirano
Odprti dostop
Using newspaper job ad text from 1960 to 2000, we measure job tasks and the adoption of individual information and communication technologies (ICTs). Most new technologies are associated with an ...increase in nonroutine analytic tasks, and a decrease in nonroutine interactive, routine cognitive, and routine manual tasks. We embed these interactions in a quantitative model of worker sorting across occupations and technology adoption. Through the lens of the model, the arrival of ICTs broadly shifts workers away from routine tasks, which increases the college premium. A notable exception is the Microsoft Office suite, which has the opposite set of effects.
Eviction and Poverty in American Cities Collinson, Robert; Humphries, John Eric; Mader, Nicholas ...
The Quarterly journal of economics,
02/2024, Letnik:
139, Številka:
1
Journal Article
Recenzirano
Abstract
More than two million U.S. households have an eviction case filed against them each year. Policy makers at the federal, state, and local levels are increasingly pursuing policies to reduce ...the number of evictions, citing harm to tenants and high public expenditures related to homelessness. We study the consequences of eviction for tenants using newly linked administrative data from two major urban areas: Cook County (which includes Chicago) and New York City. We document that before housing court, tenants experience declines in earnings and employment and increases in financial distress and hospital visits. These pre trends pose a challenge for disentangling correlation and causation. To address this problem, we use an instrumental variables approach based on cases randomly assigned to judges of varying leniency. We find that an eviction order increases homelessness and hospital visits and reduces earnings, durable goods consumption, and access to credit in the first two years. Effects on housing and labor market outcomes are driven by effects for female and Black tenants. In the longer run, eviction increases indebtedness and reduces credit scores.
Introduction
Platelet transfusion refractoriness (PTR) secondary to human leukocyte antigen (HLA) alloimmunization is a challenge in the treatment of hematology oncology patients and increases the ...risk of morbidity and mortality from bleeding events. Guidelines for treating PTR have not been clearly described in literature and the use of TPO mimetics or antifibrinolytics in routine clinical practice in the setting of PTR has not been well studied.
Aim
In this study, we aimed to describe the practice patterns for the management of PTR secondary to HLA alloimmunization, its supportive care interventions and to assess the mortality, thrombosis and bleeding related clinical outcomes at 30 days from the diagnosis of PTR and HLA alloimmunization.
Methods
A retrospective review was conducted of all PTR in adult hematology oncology patients at MD Anderson Cancer Center between May 2017 and April 2019. PTR was defined as post-transfusion platelet count increment < 10,000 per microliter in at least two consecutive occasions and within 24 hours after platelet transfusion. HLA typing, HLA antibody and platelet transfusion data were obtained from the Blood Bank Electronic records. Patient demographics and clinical data were obtained from the patients electronic medical records. The study was approved by the Institutional Review Board.
Results
A total of 51 cases of PTR secondary to HLA alloimmunization were analyzed. The majority of patients (98%) had a diagnosis of hematological malignancy of which 88.2% were undergoing active chemotherapy. Clinically relevant bleeding was observed in 33.3% while hemorrhagic shock was diagnosed in 7%. The rate of bleeding related-mortality was estimated at 7.8% (Table 1a). There was great heterogeneity in the management of bleeding risk and events. The use of antifibrinolytics and plasma products (including intravenous immunoglobulin) was more common in cases with major versus non-major bleeding (Table 1b). Grade A or B1U HLA matched products were available in less than half of cases.
Conclusions
Our study depicts several important observations related to clinical practice and supportive care during HLA platelet alloimmunization and PTR.
1. There is heterogeneity in the management of the bleeding risk and bleeding events during platelet refractoriness.
2. Antifibrinolytics are more commonly used in the patients who suffered severe bleeding.
3. Grade A and BU HLA-matched platelets are not always readily available.
4. The HLA typing and HLA antibody screen/identification testing are not always performed prior to PTR.
5. There is a significant morbidity impact on clinical outcomes due to PTR and its bleeding related complications.
Limitations of our retrospective study include the underestimation of actual bleeding outcomes and clinical reasons for the selection of supportive measures (i.e. concern for thrombosis, renal failure). Prospective randomized control trials may be able to determine the safety and efficacy of antifibrinolytics and other supportive measures in the management of PTR.
Display omitted
No relevant conflicts of interest to declare.
Phase 3 trials for patients with metastatic colorectal cancer (mCRC) have been conducted with varying designs and often with surrogate end points for overall survival (OS).
To critically examine the ...factors associated with clinically relevant improvement in OS (defined as ≥2 months) in these trials and to evaluate their association with outcomes reflected in Surveillance, Epidemiology, and End Results (SEER) registry data.
Medline, EMBASE, Cochrane, Web of Science, ClinicalTrials.gov, EU Clinical Trials Register, and the International Clinical Trials Registry Platform were searched for phase 3 trials of systemic therapy for patients with mCRC by decade (1986-1996, 1997-2006, and 2007-2016), excluding early or pilot studies, studies that did not involve an anticancer drug, studies on cancer screening and prevention, reports of pooled data from multiple trials, and studies with nonpharmaceutical approaches. The association of drug development with OS outside the clinical trial setting was evaluated using data from the SEER registry, including adult patients with a primary cancer site in the colon or rectum, including adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma; a distant stage; and receipt of chemotherapy as first-line therapy. Kaplan-Meier curves and log-rank tests were used to assess OS.
The literature search identified 150 phase III clinical trials with 77 494 total enrollments, and 67 126 patients with mCRC were identified from the SEER database. Significant increases in survival were noted over time, best reflected in the experimental arm of first-line therapy (OS increased by 5.7 months per 10 years; 95% CI, 4.7-6.6 months; progression-free survival increased by 1.4 months per 10 years; 95% CI, 0.7-2.1 months). Although 69 of 148 trials (46.6%) met their predefined primary end point (including 20 of 44 trials 45.5% with OS as the primary end point), only 35 of 132 trials (26.5%) resulted in improvement in OS by 2 months or more (including 13 of 42 trials 31.0% with OS as the primary end point). Multivariable logistic regression showed that third-line therapies or later (odds ratio, 0.57; 95% CI, 0.51-0.63) and funding by pharmaceutical companies (odds ratio, 0.57; 95% CI, 0.54-0.60) were less often associated with improvement in OS. Furthermore, there was a decrease in the novelty of targets and agents over time, with trials that evaluated regimens composed entirely of previously approved drugs for mCRC increasing from 28% to 50%. Data from the SEER database showed that median OS increased from 12 months (95% CI, 12-13 months) (1986-1996) to 21 months (95% CI, 21-22 months) (2007-2015) (P < .001), but the 5-year OS continued to be low at 12.2% in 2011.
In this systematic review, OS for patients with mCRC appeared to improve significantly in trials, translating into meaningful benefits outside the clinical trial setting; however, these advances, although significant cumulatively, are largely incremental individually. These data should be a call to aim for larger gains from future trials with novel drugs, building on the increasing understanding of the biology of mCRC and sophisticated translational research tools.
Current strategies to suppress graft-versus-host disease (GVHD) also compromise graft-versus-tumor (GVT) responses. Furthermore, most experimental strategies to separate GVHD and GVT responses merely ...spare GVT function without actually enhancing it. We have previously shown that endogenously expressed TNF-related apoptosis-inducing ligand (TRAIL) is required for optimal GVT activity against certain malignancies in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In order to model a donor-derived cellular therapy, we genetically engineered T cells to overexpress TRAIL and adoptively transferred donor-type unsorted TRAIL+ T cells into mouse models of allo-HSCT. We found that murine TRAIL+ T cells induced apoptosis of alloreactive T cells, thereby reducing GVHD in a DR5-dependent manner. Furthermore, murine TRAIL+ T cells mediated enhanced in vitro and in vivo antilymphoma GVT response. Moreover, human TRAIL+ T cells mediated enhanced in vitro cytotoxicity against both human leukemia cell lines and against freshly isolated chronic lymphocytic leukemia (CLL) cells. Finally, as a model of off-the-shelf, donor-unrestricted antitumor cellular therapy, in vitro-generated TRAIL+ precursor T cells from third-party donors also mediated enhanced GVT response in the absence of GVHD. These data indicate that TRAIL-overexpressing donor T cells could potentially enhance the curative potential of allo-HSCT by increasing GVT response and suppressing GVHD.
Abstract 1847
Aminopeptidases (AP) are necessary for the growth and development of malignant cells and have a selectively important role in the maintenance of intracellular amino acid (AA) levels in ...neoplastic cells. CHR2797 is a novel, low nanomolar inhibitor of the M1 family of AP, a group of metalloenzymes containing a central Zn2+ ion. CHR2797 has antiproliferative and apoptotic effects against MM in vitro by inducing the AA deprivation response (AADR). TST, an oral, chronically administered agent with a good safety profile has demonstrated activity in patients with relapsed/refractory AML and is currently under study as part of combination therapy for untreated elderly patients with AML. At the epigenetic regulatory level, Zn-dependent histone deacetylase (HDAC) cause the deacetylation of histone and non-histone cellular proteins which are critical for gene expression, inducing apoptosis and cell cycle arrest in cancer cells. LBH589 (Panobinostat) is an established pan-HDAC inhibitor with potent in vitro anti-cancer activity in many hematological malignancies. The clinical efficacy of Panobinostat is currently being studied in several Phase II/III clinical trials with particular promise seen in the treatment of MM. Here we examined the potential therapeutic effect of CHR2797, alone and with LBH589, against MM cells. Using MTS and CTG assays, CHR2797, at clinically achievable concentrations, decreased survival and proliferation in MM1S and IL-6-dependent ANBL6 cells, in the presence or absence of bone marrow stromal cells following 72 hours incubation. CHR2797 induces apoptosis in MM cells via activation of Caspase 3/7 and 9 but not Caspase 8. Significantly, CHR2797 (10 μM) induced apoptosis in patient MM cells, as seen by % of annexin V and PI from 22 + 1.5% to 39 + 2.3% after 48h incubation. Combined treatment with CHR2797 and LBH589 in MM cells (MM1S, ANBL6, and INA6) further reduced cell viability following 72 hour incubation when compared with CHR2797 treatment alone, as determined by CTG viability luminescent assay. Both drugs together also augmented growth inhibitory effects when compared with single agent alone, after 72 hours incubation followed by MTS assay. Importantly, the combination of both drugs increased caspase 3/7- & 9-mediated apoptosis than CHR2797 alone in these MM cells following 24h-treatment. Cell cycle analysis (CHR2797 at 1μM; LBH589 at 1 nM) showed an increased growth arrest in G0/G1 cells in MM1R cells treated with both drugs versus CHR2797 alone after 24 hours: 68.5±3.3% versus 36±2.5%. Furthermore, CHR2797 inhibited anti-apoptotic protein Mcl-1 in MM1R and U266 MM cells by immunoblottings. Combined treatment with CHR2797 and LBH589 further blocked Mcl-1 when compared with either treatment alone after 24 hours incubation. Together, these results show that the combination of CHR2797 and LBH589 enhanced anti-myeloma effects when compared with either drug alone. This combination, which also has the potential of being without overlapping clinical toxicities, provides a promising novel approach to anti-myeloma therapy.
Singer:Cell Therapeutics, Inc: Employment, Equity Ownership. Richardson:Novartis: Membership on an entity's Board of Directors or advisory committees.
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