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In 2010, the United States Congress placed a moratorium on earmarks – congressionally mandated spending projects. But did the earmark moratorium actually rid public policy of earmarks? I use earmark data and 2010–2020 state-level highway funding metrics to examine the relationship between previously expired transportation earmarks and federal highway funding during the earmark moratorium. Earmarks in the 2005 surface transportation law (SAFETEA-LU) continued to benefit certain states in 2020, even though the projects technically expired in 2009. This is because the funding “formulas” established by all post-2009 surface transportation laws were fully determined by the highway allocation percentage each state received in the preceding year, inclusive of earmarks. Further, I find the relationship between SAFETEA-LU earmarks and state funding disparities strengthened from 2010 to 2020, meaning the expired earmarks increased in policy significance during the moratorium. Highly earmarked states became even more advantaged after the earmarks were institutionalised into the highway funding formula.

Bringing home federal spending projects to the district is a common reelection strategy for members of the U.S. Congress, and congresswomen tend to outperform congressmen in securing district spending. However, for legislators to turn distributive benefits into higher approval and electoral rewards, constituents must recognize that public spending has taken place in their community and attribute credit to the correct public official. I theorize that congresswomen face a gender bias when claiming credit for federal projects, and I test this theory through an online survey experiment. Contrary to expectations, I find no evidence that legislator gender influences the public’s reaction to congressional credit claims, indicating that congresswomen can effectively use distributive politics to counter gendered vulnerability in the U.S. Congress. This research advances the literature on gender and politics by investigating whether a gender bias in credit claiming prevents congresswomen from turning their representational efforts into electoral capital.

Conventional wisdom has long assumed veteran status to be a beneficial credential for political candidates, but the evidence is mixed on the direct association between military experience and electoral success. Rather than a uniformly advantageous candidate characteristic, we argue veteran status is best understood as an influential source cue and issue ownership factor that can be capitalized on by effective campaign messaging. We outline three potential mechanisms through which veteran candidates unlock electoral gains – solidified issue ownership, enhanced trait ownership, and increased salience of advantageous policy issues. We test these expectations with two online survey experiments, randomizing a fictional candidate’s veteran status and the policy topic discussed in campaign messaging. We find veteran candidates can use a combination of veteran cues and policy messaging to gain an advantage over nonveterans. However, veteran candidates stand to benefit most by talking about crime rather than national defense, as a ceiling effect limits veterans’ ability to enhance their service-related issue and trait ownership ratings by messaging on national defense. By reconceptualizing military service as an effective communication tool rather than a uniformly advantageous biographical line, we clarify the substantial electoral value of veteran status in American politics. More broadly, our findings show that voters respond not just to individual cues derived from partisanship or a candidate’s background, but to the interaction of these cues with campaign messaging.

Standard treatments for indolent non-Hodgkin lymphomas are often toxic, and most patients ultimately relapse. Lenalidomide, an immunomodulatory agent, is effective as monotherapy for relapsed indolent non-Hodgkin lymphoma. We assessed the efficacy and safety of lenalidomide plus rituximab in patients with untreated, advanced stage indolent non-Hodgkin lymphoma. In this phase 2 trial, undertaken at one instution, patients with follicular lymphoma and marginal zone lymphoma were given lenalidomide, orally, at 20 mg/day on days 1–21 of each 28-day cycle. For patients with small lymphocytic lymphoma, dosing began at 10 mg/day to avoid tumour flare, with an escalation of 5 mg/month to 20 mg/day. Rituximab was given at 375 mg/m2 as an intravenous infusion on day 1 of each cycle. Patients responding after six cycles could continue therapy for up to 12 cycles. The primary endpoint was overall response, defined as the proportion of patients who achieved a partial or complete response; patients were assessed for response if they had any post-baseline tumour assessment. This trial is registered with ClinicalTrials.gov, number NCT00695786. 110 patients with follicular lymphoma (n=50), marginal zone lymphoma (n=30), and small lymphocytic lymphoma (n=30) were enrolled from June 30, 2008, until Aug 12, 2011. 93 of 103 evaluable patients had an overall response (90%, 95% CI 83–95). Complete responses occurred in 65 (63%, 95% CI 53–72) and partial responses in 28 patients (27%, 19–37). Of 46 evaluable patients with follicular lymphoma, 40 (87%) patients had a complete response and five (11%) had a partial response. Of 27 evaluable patients with marginal zone lymphoma, 18 (67%) had a complete response and six (22%) had a partial response. Of 30 evaluable patients with small lymphocytic lymphoma, seven (23%) had a complete response and 17 (57%) had a partial response. The most common grade 3 or 4 adverse events were neutropenia (38 [35%] of 110 patients), muscle pain (ten [9%]), rash (eight [7%]), cough, dyspnoea, or other pulmonary symptoms (five [5%]), fatigue (five [5%]), thrombosis (five [5%]), and thrombocytopenia (four [4%]). Lenalidomide plus rituximab is well tolerated and highly active as initial treatment for indolent non-Hodgkin lymphoma. An international phase 3 study (NCT01476787) to compare this regimen with chemotherapy in patients with untreated follicular lymphoma is in progress. Celgene Corporation and Richard Spencer Lewis Memorial Foundation and Cancer Center Support Grant.

While a large body of research explores the federal-level influences over distributive politics decisions, very little attention has been given to the active role state and local governments play in the geographic distribution of federal funds. Before presidents, legislators, and agency leaders can influence the selection of federal grants, state and local governments must expend time and resources to submit grant proposals. We focus on grant applications as our unit of analysis and advance a theory that congressional representation influences the grant application behavior of state and local governments. We analyze US Department of Transportation grant applications and awards from 2009 to 2022 and find evidence that congressional representation meaningfully influences state-level grant application behavior. States apply more aggressively for federal transportation grants when represented by senators in the Senate majority party, and states apply more efficiently for grants when represented by a senator holding an advantageous committee leadership post.

The combination of rituximab and lenalidomide has shown promise for the treatment of mantle-cell lymphoma (MCL) in preclinical studies. We aimed to identify the maximum tolerated dose (MTD) of lenalidomide when combined with rituximab in a phase 1 trial and to assess the efficacy and safety of this combination in a phase 2 trial in patients with relapsed or refractory MCL. Patients with relapsed or refractory MCL who had received one to four previous lines of treatment were enrolled in this single-arm, open-label, phase 1/2 trial at MD Anderson Cancer Center. In phase 1, to identify the MTD of lenalidomide, four patient cohorts received escalating doses (10, 15, 20, and 25 mg) of daily oral lenalidomide on days 1–21 of each 28-day cycle. 375 mg/m2 intravenous rituximab was also administered in four weekly doses during cycle 1 only. In phase 2, patients received rituximab plus the MTD of lenalidomide, following the same cycles as for phase 1. Treatment in both phases continued until disease progression, stem-cell transplantation, or severe toxicity. The primary efficacy endpoint was overall response (complete or partial response). The secondary efficacy endpoint was survival. We used the Kaplan-Meier method to estimate response duration, progression-free survival, and overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00294632. 52 patients were enrolled between Feb 10, 2006 and July 30, 2009, 14 in phase 1 and 44 (including six patients who received the MTD of lenalidomide in the phase 1 portion) in phase 2. The MTD was 20 mg lenalidomide. One patient who was treated with 25 mg lenalidomide developed a grade 4 non-neutropenic infection and died. In the phase 2 portion of the study, grade 3–4 haematological toxicities included neutropenia (29 patients), lymphopenia (16 patients), leucopenia (13 patients), and thrombocytopenia (ten patients). There were only two episodes of febrile neutropenia. Among 44 patients in phase 2, 25 (57%) had an overall response: 16 (36%) had a complete response and nine (20%) had a partial response. The median response duration was 18·9 months (95% CI 17·0 months to not reached [NR]). The median progression-free survival was 11·1 months (95% CI 8·3 to 24·9 months), and the median overall survival was 24·3 months (19·8 months to NR). Five of 14 patients who had received bortezomib treatment before enrolment achieved an overall response. Oral lenalidomide plus rituximab is well tolerated and effective for patients with relapsed or refractory MCL. Celgene.

Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.

The serotonergic 5-HT1A receptor is known to be involved in both impulsivity and anxiety-related behavior. Although anxiety and impulsivity are different constructs, it has been shown that anxiogenesis can result in impulsiveness. It is therefore important to determine if the 5-HT1A receptor is involved in the commission of impulsive actions independent of its effects on anxiety. The 5-HT1A agonist 8-OH-DPAT (0.0125–0.1 mg/kg subcutaneous) increased impulsive action at low doses, but decreased it at higher doses, on the novel paced variable consecutive number with discriminative stimulus task (VCN). Neither the 5-HT1A antagonist WAY 100,635 (0.2–1.2 mg/kg subcutaneous), nor the noradrenergic antagonist and pharmacological stressor yohimbine (1–2 mg/kg intraperitoneal) altered measures of impulsivity. Stress induced by yohimbine was sufficient to produce anxiety-like behavior in the elevated zero maze, confirming that the VCN task is a selective assay of impulsive action that is not affected by anxiety. We hypothesize that the biphasic effect of 8-OH-DPAT is due to actions on presynaptic raphe 5-HT1A autoreceptors, and also postsynaptic 5-HT1A receptors. These results suggest that this receptor mediates impulsive action and that this is not secondary to its role in anxiety.

Drugs that interfere with cannabinoid CB1 transmission suppress various food-motivated behaviors, and it has been suggested that such drugs could be useful as appetite suppressants. Biochemical studies indicate that most of these drugs assessed thus far have been CB1 inverse agonists, and although they have been shown to suppress food intake, they also appear to induce nausea and malaise. The present studies were undertaken to characterize the behavioral effects of AM4113, which is a CB1 neutral antagonist, and to examine whether this drug can reduce food-reinforced behaviors and feeding on diets with varying macronutrient compositions. Biochemical data demonstrated that AM4113 binds to CB1 receptors, but does not show inverse agonist properties (ie no effects on cyclic-AMP production). In tests of spontaneous locomotion and analgesia, AM4113 reversed the effects of the CB1 agonist AM411. AM4113 suppressed food-reinforced operant responding with rats responding on fixed ratio (FR) 1 and 5 schedules of reinforcement in a dose-dependent manner, and also suppressed feeding on high-fat, high-carbohydrate, and lab chow diets. However, in the same dose range that suppressed feeding, AM4113 did not induce conditioned gaping, which is a sign of nausea and food-related malaise in rats. These results suggest that AM4113 may decrease appetite by blocking endogenous cannabinoid tone, and that this drug may be less associated with nausea than CB1 inverse agonists.