Conditional Federal Spending as a Regulatory Device

In this Article, Professor Rosenthal notes that the federal spending power is an important tool for shaping our economy, our government, and our society. However, government money is often used to induce or deter conduct by imposing certain restrictions on its receipt. The questions arises of what are the tests for the constitutionality of conditional spending. The author points out that there has not been a single case in which conditional federal spending has been declared invalid by the Supreme Court. He discusses two Supreme Court cases on the topic of government spending. Due to the importance of the topic and the little attention it has received, the author advocates the formulation of satisfactory principles in order to maintain proper constitutional balance

The Constitution, Congress, and Presidential Elections

It has been recommended by a prestigious commission of the American Bar Association and endorsed by the ABA\u27s House of Delegates. The Bar Association of the City of New York, which had previously recommended a different proposed amendment, has now shifted its support to direct popular vote, as has Senator Birch Bayh, Chairman of the Subcommittee on Constitutional Amendments of the Senate Committee on the Judiciary. A Gallup poll indicates that 66 per cent of the nation supports this amendment, with only 19 per cent opposed. It must be remembered, however, that a decision to amend the Constitution is, as a practical matter, usually an irreversible step. It is the purpose of this Article to examine the gravity of the evils sought to be eliminated, the possibility that the proposed amendment might give rise to undesirable side effects, and the availability of alternative remedies

Use of Balloon-Tipped Catheters in the Critically Ill Child

A retrospective study of our experience in the placement of 19 consecutive balloon-tipped catheters in the pulmonary artery of 18 children disclosed that the procedure can be performed with relative ease in the intensive care unit without the aid of fluoroscopy. Insertion of the catheters was not associated with any serious complications. Catheter malfunction, however, occurred in 9 of 18 patients: balloon rupture in 6 and clot formation in 3. Comparison of pulmonary capillary pressure through a balloon-tipped catheter and venous pressure through a central venous line indicates that, in the absence of significant pulmonary disease requiring high positive end expiratory pressure, or significant left heart dysfunction, a central venous pressure line is frequently adequate for monitoring right heart pressures and as a guidance to fluid therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67256/2/10.1177_000992288202100302.pd

Long and short paths in uniform random recursive dags

In a uniform random recursive k-dag, there is a root, 0, and each node in turn, from 1 to n, chooses k uniform random parents from among the nodes of smaller index. If S_n is the shortest path distance from node n to the root, then we determine the constant \sigma such that S_n/log(n) tends to \sigma in probability as n tends to infinity. We also show that max_{1 \le i \le n} S_i/log(n) tends to \sigma in probability.Comment: 16 page

Sulfadoxine-pyrimethamine plus chloroquine or amodiaquine for uncomplicated falciparum malaria: a randomized, multisite trial to guide national policy in Uganda.

The use of combinations of inexpensive drugs for the treatment of malaria in Africa has been proposed as an interim policy while awaiting the widespread availability of more effective regimens. We compared sulfadoxine-pyrimethamine plus chloroquine or amodiaquine in three districts in Uganda. Patients aged 6 months or greater with uncomplicated falciparum malaria were enrolled and randomized to therapy. Safety, tolerability, and efficacy outcomes, adjusted by genotyping, were assessed over 28 days. Of 1,105 patients enrolled, 1,057 (96%) completed follow-up. For children less than 5 years old, the risk of clinical treatment failure adjusted by genotyping at the three sites ranged from 34% to 67% with chloroquine plus sulfadoxine-pyrimethamine and from 13% to 35% with amodiaquine plus sulfadoxine-pyrimethamine (risk differences 21-32%, P < 0.0001 at all sites). Serious adverse events were uncommon with both regimens. The risk of treatment failure with chloroquine plus sulfadoxine-pyrimethamine, the current standard in Uganda, was unacceptably high. Amodiaquine plus sulfadoxine-pyrimethamine was significantly more efficacious; however, existing levels of resistance raises concern about the useful therapeutic life-span of this regimen

Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Although an increasing number of genetic factors have been connected to this debilitating condition, the proportion of cases that can be attributed to distinct genetic defects is unknown. To provide a comprehensive analysis of the frequency and spectrum of pathogenic missense mutations and coding risk variants in nine genes previously implicated in DLB, we performed exome sequencing in 111 pathologically confirmed DLB patients. All patients were Caucasian individuals from North America. Allele frequencies of identified missense mutations were compared to 222 control exomes. Remarkably, ~ 25% of cases were found to carry a pathogenic mutation or risk variant in APP, GBA or PSEN1, highlighting that genetic defects play a central role in the pathogenesis of this common neurodegenerative disorder. In total, 13% of our cohort carried a pathogenic mutation in GBA, 10% of cases carried a risk variant or mutation in PSEN1, and 2% were found to carry an APP mutation. The APOE ε4 risk allele was significantly overrepresented in DLB patients (p-value < 0.001). Our results conclusively show that mutations in GBA, PSEN1, and APP are common in DLB and consideration should be given to offer genetic testing to patients diagnosed with Lewy body dementia

Artemisinin versus Nonartemisinin Combination Therapy for Uncomplicated Malaria: Randomized Clinical Trials from Four Sites in Uganda

BACKGROUND: Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently to improve efficacy and limit the spread of resistance, but artemisinins are expensive and relatively untested in highly endemic areas. We compared artemisinin-based and other combination therapies in four districts in Uganda with varying transmission intensity. METHODS AND FINDINGS: We enrolled 2,160 patients aged 6 mo or greater with uncomplicated falciparum malaria. Patients were randomized to receive chloroquine (CQ) + sulfadoxine-pyrimethamine (SP); amodiaquine (AQ) + SP; or AQ + artesunate (AS). Primary endpoints were the 28-d risks of parasitological failure either unadjusted or adjusted by genotyping to distinguish recrudescence from new infections. A total of 2,081 patients completed follow-up, of which 1,749 (84%) were under the age of 5 y. The risk of recrudescence after treatment with CQ + SP was high, ranging from 22% to 46% at the four sites. This risk was significantly lower (p < 0.01) after AQ + SP or AQ + AS (7%–18% and 4%–12%, respectively). Compared to AQ + SP, AQ + AS was associated with a lower risk of recrudescence but a higher risk of new infection. The overall risk of repeat therapy due to any recurrent infection (recrudescence or new infection) was similar at two sites and significantly higher for AQ + AS at the two highest transmission sites (risk differences = 15% and 16%, p< 0.003). CONCLUSION: AQ + AS was the most efficacious regimen for preventing recrudescence, but this benefit was outweighed by an increased risk of new infection. Considering all recurrent infections, the efficacy of AQ + SP was at least as efficacious at all sites and superior to AQ + AS at the highest transmission sites. The high endemicity of malaria in Africa may impact on the efficacy of artemisinin-based combination therapy. The registration number for this trial is ISRCTN67520427 (http://www.controlled-trials.com/isrctn/trial/|/0/67520427.html)