The Much Maligned 527 and Institutional Choice

The continuing controversy over “527” organizations has led Congress to impose extensive disclosure requirements on these political organizations and to consider imposing extensive restrictions on their funding as well. The debate about what laws should govern these entities has, however, so far almost completely ignored the fact that such laws raise a complicated institutional choice question. This Article seeks to resolve that question by developing a new institutional choice framework to guide this and similar choices. The Article first explores the context for making this determination by describing the current laws governing 527s, including both federal election laws administered by the Federal Election Commission and federal tax laws administered by the Internal Revenue Service. The Article then proposes and applies an institutional choice framework to guide the decision of into which body of substantive law the current and proposed rules for 527s should be incorporated. The Article concludes that while regulation of political activity through both election law and tax law can work reasonably well, the different tasks for which these bodies of law and their implementing agencies are best suited require a different allocation of responsibilities than both current and proposed laws governing 527s provides. Finally, the Article identifies other areas that may benefit from application of this framework

Globalization Without a Safety Net: The Challenge of Protecting Cross-Border Funding of NGOs

More than 50 countries around the world have sharply increased legal restrictions on both domestic non-governmental organizations (“NGOs”) that receive funding from outside their home country and the foreign NGOs that provide such funding and other support. These restrictions include requiring advance government approval before a domestic NGO can accept cross-border funding, requiring such funding to be routed through government agencies, and prohibiting such funding for NGOs engaged in certain activities. Publicly justified by national security, accountability, and other concerns, these measures often go well beyond what is reasonably supported by such legitimate interests. These restrictions therefore violate international law, which provides that the right to receive such funding is an essential aspect of freedom of association. Yet affected NGOs cannot rely on the international human rights treaties that codify this right because those treaties have limited reach and lack effective avenues for remedying these violations. There is, however, a growing web of international investment treaties designed to protect cross-border flows of funds, leading some supporters of cross-border funding for NGOs to argue that NGOs can instead use these investment treaties to protect such funding. In this Article, I provide the most thorough consideration of this proposal to date, including taking into account not only the legal hurdles to invoking investment treaty protections in this context but also the practical hurdles based on recently gathered information regarding the costs to parties who pursue claims under these treaties. I conclude that while it may be possible to overcome both sets of hurdles in some situations, these hurdles are higher than previous commentators have acknowledged. In particular, overcoming the high costs of bringing claims under these treaties would at a minimum require a concerted effort to fund or reduce such costs through either securing substantial third party financing or recruiting significant pro bono assistance. Given these obstacles to invoking the protections of international investment treaties, I then explore the insights that the remarkable growth in such treaties provide regarding the conditions that would need to exist for countries to be convinced to enact a similar set of agreements to protect cross-border funding of NGOs. I conclude that such conditions are currently absent and that it will take many years to see if they could develop, even assuming that many countries continue to increasingly restrict or effectively prohibit such funding. In the meantime, both recipients and providers of cross-border funding for NGOs will need to consider alternate strategies that do not rely on international law to counter such restrictions

Allocating State Authority Over Charitable Nonprofit Organizations

This Essay considers the allocation of state authority to enforce the legal obligations particular to charities and their leaders among state officials, including attorneys general, judges, and legislators, and private parties. It first describes the existing allocation. It then reviews the most common criticisms of this allocation, which primarily focus on two concerns: politicization and lack of sufficient enforcement. Finally, it evaluates the most notable proposals for reallocating this authority, including the reallocation of this authority in part to private parties. This Essay concludes that reform proposals have two fundamental flaws. First, proposals aimed at countering the political nature of state attorney general decisions fail to consider both the advantages of that nature and the existing restraints placed on it by state courts and resource limitations. Second, proposals aimed at addressing the admittedly low level of oversight provided by state attorneys general assume that there is significant undiscovered malfeasance at charities, the countering of which would justify the burdens these proposals would place on all charities, even though empirical data supporting this assumption are lacking. That said, this Essay supports more modest reforms. These are: requiring all attorney general negotiated settlements to be submitted to state courts for approval; permitting derivative suits by current fiduciaries, as is the law in most states, and by a significant proportion of members, as is the law in some states; and modestly expanding donor standing to allow substantial donors (but not their successors or heirs) to enforce explicit written terms on substantial gifts. These reforms would strengthen existing state oversight while being unlikely to significantly burden most charities

Enteroendocrine cells express functional Toll-like receptors

Intestinal epithelial cells (IECs) provide a physical and immunological barrier against enteric microbial flora. Toll-like receptors (TLRs), through interactions with conserved microbial patterns, activate inflammatory gene expression in cells of the innate immune system. Previous studies of the expression and function of TLRs in IECs have reported varying results. Therefore, TLR expression was characterized in human and murine intestinal sections, and TLR function was tested in an IEC line. TLR1, TLR2, and TLR4 are coexpressed on a subpopulation of human and murine IECs that reside predominantly in the intestinal crypt and belong to the enteroendocrine lineage. An enteroendocrine cell (EEC) line demonstrated a similar expression pattern of TLRs as primary cells. The murine EEC line STC-1 was activated with specific TLR ligands: LPS or synthetic bacterial lipoprotein. In STC-1 cells stimulated with bacterial ligands, NF-κB and MAPK activation was demonstrated. Furthermore, the expression of TNF and macrophage inhibitory protein-2 were induced. Additionally, bacterial ligands induced the expression of the anti-inflammatory gene transforming growth factor-β. LPS triggered a calcium flux in STC-1 cells, resulting in a rapid increase in CCK secretion. Finally, conditioned media from STC-1 cells inhibited the production of nitric oxide and IL-12 p40 by activated macrophages. In conclusion, human and murine IECs that express TLRs belong to the enteroendocrine lineage. Using a murine EEC model, a broad range of functional effects of TLR activation was demonstrated. This study suggests a potential role for EECs in innate immune responses

The natural history of egg allergy in an observational cohort

There are few studies on the natural history of egg allergy and most are single site, not longitudinal, and have not identified early predictors of outcomes

The natural history of milk allergy in an observational cohort

There are few studies on the natural history of milk allergy. Most are single-site and not longitudinal, and these have not identified a means for early prediction of outcomes

Rare region effects at classical, quantum, and non-equilibrium phase transitions

Rare regions, i.e., rare large spatial disorder fluctuations, can dramatically change the properties of a phase transition in a quenched disordered system. In generic classical equilibrium systems, they lead to an essential singularity, the so-called Griffiths singularity, of the free energy in the vicinity of the phase transition. Stronger effects can be observed at zero-temperature quantum phase transitions, at nonequilibrium phase transitions, and in systems with correlated disorder. In some cases, rare regions can actually completely destroy the sharp phase transition by smearing. This topical review presents a unifying framework for rare region effects at weakly disordered classical, quantum, and nonequilibrium phase transitions based on the effective dimensionality of the rare regions. Explicit examples include disordered classical Ising and Heisenberg models, insulating and metallic random quantum magnets, and the disordered contact process.Comment: Topical review, 68 pages, 14 figures, final version as publishe

Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3

The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease compared to non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to Crohn’s disease etiology in this population, most notably at NOD2, in which three causal, uncommon, and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes which showed significantly greater association to Crohn’s disease in the Ashkenazi Jewish population compared to a non-Jewish population (145 haplotypes and no haplotypes with P-value < 10−3, respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established Crohn’s disease loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in TRPM2 on chromosome 21. Within the chromosome 16 region, R642S of HEATR3 and rs9922362 of BRD7 showed genome-wide significance. Expression studies of HEATR3 demonstrated a positive role in NOD2-mediated NF-κB signaling. The BRD7 signal showed conditional dependence with only the downstream rare Crohn’s disease-causal variants in NOD2, but not with the background haplotype; this elaborates NOD2 as a key illustration of synthetic association

Tacrolimus for the treatment of fistulas in patients with crohn’s disease: a randomized, placebo-controlled trial

AbstractBackground & Aims:This study determined the effectiveness of tacrolimus for the treatment of Crohn's disease fistulas.Methods:The study was a randomized, double-blind, placebo-controlled, multicenter clinical trial. Forty-eight patients with Crohn's disease and draining perianal or enterocutaneous fistulas were randomized to treatment with oral tacrolimus 0.2 mg · kg−1 · day−1 or placebo for 10 weeks. The primary outcome measure was fistula improvement as defined by closure of ≥50% of particular fistulas that were draining at baseline and maintenance of that closure for at least 4 weeks. A secondary outcome measure was fistula remission as defined by closure of all fistulas and maintenance of that closure for at least 4 weeks.Results:Forty-three percent of tacrolimus-treated patients had fistula improvement compared with 8% of placebo-treated patients (P = 0.004). Ten percent of tacrolimus-treated patients had fistula remission compared with 8% of placebo-treated patients (P = 0.86). Adverse events significantly associated with tacrolimus, including headache, increased serum creatinine level, insomnia, leg cramps, paresthesias, and tremor, were managed with dose reduction.Conclusions:Oral tacrolimus 0.2 mg · kg−1 · day−1 is effective for fistula improvement, but not fistula remission, in patients with perianal Crohn's disease. Adverse events associated with tacrolimus can be managed by dose reduction. Lower doses of tacrolimus should be evaluated