Governing biological material at the intersection of care and research: the use of dried blood spots for biobanking

A series of governance issues currently surrounds the multiple uses and multiple users of dried blood spots (DBS) for research purposes. Internationally there is a discussion on storing DBS resulting from newborn screening for public health and using them as the basis for large biobank-like collections to facilitate biomedical research. If such a transformation were to be formalized, then DBS would sit at the intersection of care (ie, public health) and research, with the mechanisms through which such a collection could be managed not totally self-evident. What is more, a DBS collection raises questions about the fuzzy boundaries between privacy and anonymity; how to control or define quality control uses of DBS; medical vs nonmedical uses; as well as benefit sharing and stakeholder involvement. Our goal here is to explore some of the key questions relating to DBS governance by way of the bio-objects and bio-objectification concepts. By embracing – rather than resisting to – the blurring of boundaries and problems in categorization that have come to characterize bio-objects and bio-objectification processes recently described in this journal, we attempt to highlight some issues that might not be currently considered, and to point to some possible directions to go (or avoid). Building from our knowledge of the current DBS situation in the Netherlands, we outline questions concerning the uses, management, collection, and storage of DBS

Giant Alcohol: A Worthy Opponent for the Children of the Band of Hope

From its foundation in 1847, the temperance organisation the Band of Hope addressed its young members as consumers, victims, and agents. In the first two roles they encountered the effects of drink of necessity, but in the third role they were encouraged to seek it out, attempting to influence individuals and wider society against 'Giant Alcohol'. With an estimated membership of half the school-age population by the early twentieth century, well over three million, the Band of Hope also acted more directly to influence policy, and encouraged young people to consider issues of policy and politics. With its wide range of activities and material to educate, entertain and empower millions of children, and its radical view of the place of the child, the Band of Hope not only mobilised its child members to lobby for legal change, including prohibition, but took an active part in pointing out the cost of alcohol to society, particularly during the 14-18 war. The organisation began to decline post 1918, and this paper focuses on the address made to children by the Band of Hope in the late nineteenth and early twentieth centuries, at a time when its innovative view of children as able to understand and influence policy decisions reflected developments in the construction of childhood. This article draws on the archive of the British National Temperance League, over 50,000 items located in the Livesey Collection, University of Central Lancashire

D1-D5 on ALE Space

We construct a two-dimensional N=(0,4) quiver gauge theory on D1-brane probing D5-branes on ALE space, and study its IR behavior. This can be thought of as a gauged linear sigma model for the NS5-branes on ALE space.Comment: 17 pages, 1 figure, lanlmac; v2: reference adde

Thermodynamics of doubly charged CGHS model and D1-D5-KK black holes of IIB supergravity

We study the doubly charged Callan-Giddings-Harvey-Strominger (CGHS) model, which has black hole solutions that were found to be U-dual to the D1-D5-KK black holes of the IIB supergravity. We derive the action of the model via a spontaneous compactification on S^3 of the IIB supergravity on S^1*T^4 and obtain the general static solutions including black holes corresponding to certain non-asymptotically flat black holes in the IIB supergravity. Thermodynamics of them is established by computing the entropy, temperature, chemical potentials, and mass in the two-dimensional setup, and the first law of thermodynamics is explicitly verified. The entropy is in precise agreement with that of the D1-D5-KK black holes, and the mass turns out to be consistent with the infinite Lorentz boost along the M theory circle that is a part of the aforementioned U-dual chain.Comment: 21 pages, Revte

String Tensions and Three Dimensional Confining Gauge Theories

In the context of gauge/gravity duality, we try to understand better the proposed duality between the fractional D2-brane supergravity solutions of (Nucl. Phys. B 606 (2001) 18, hep-th/0101096) and a confining 2+1 dimensional gauge theory. Based on the similarities between this fractional D2-brane solution and D3-brane supergravity solutions with more firmly established gauge theory duals, we conjecture that a confining q-string in the 2+1 dimensional gauge theory is dual to a wrapped D4-brane. In particular, the D4-brane looks like a string in the gauge theory directions but wraps a S**3 in S**4 in the transverse geometry. For one of the supergravity solutions, we find a near quadratic scaling law for the tension: $T \sim q (N-q)$. Based on the tension, we conjecture that the gauge theory dual is SU(N) far in the infrared. We also conjecture that a quadratic or near quadratic scaling is a generic feature of confining 2+1 dimensional SU(N) gauge theories.Comment: 23 pages, 2 figure

Effectiveness of Efavirenz-Based Regimens in Young HIV-Infected Children Treated for Tuberculosis: A Treatment Option for Resource-Limited Settings

Background: Antiretroviral treatment (ART) options for young children co-infected with HIV and tuberculosis are limited in resource-poor settings due to limited data on the use of efavirenz (EFV). Using available pharmacokinetic data, an EFV dosing schedule was developed for young co-infected children and implemented as the standard of care at Macha Hospital in Southern Province, Zambia. Treatment outcomes inchildren younger than 3 years of age or weighing less than 10 kg receiving either EFV-based ART plus anti-tuberculous treatment or nevirapine-based (NVP) ART were compared. Methods: Treatment outcomes were measured in a cohort of HIV-infected children seeking care at Macha Hospital in rural Zambia from 2007 to 2010. Informationon the diagnosis and treatment of tuberculosis was abstracted from medical records. Results: Forty-five children treated for tuberculosis initiated an EFV-based regimen and 69 children initiated a NVP-based regimen, 7 of whom also were treated for tuberculosis. Children receiving both regimens were comparable in age, but children receiving EFV started ART with a lower CD4+ T-cell percentage and weight-for-age z-score. Children receiving EFV experienced increases in both CD4+ T-cell percentage and weight-for-age z-score during follow-up, such that levels were comparable to children receiving NVP after two years of ART. Cumulative survival after 12 months of ART did not differ between groups (NVP:87%;EFV:80%;p = 0.25). Eleven children experienced virologic failure during follow-up.The adjusted hazard ratio of virologic failure comparing EFV to NVP was 0.25 (95% CI:0.05,1.24) and 0.13 (95% CI:0.03,0.62) using thresholds of 5000 and 400 copies/mL, respectively.Five children receiving EFV were reported to have had convulsions after ART initiation compared to only one child receiving NVP (p = 0.04). Conclusions: Despite poorer health at ART initiation, children treated for tuberculosis and receiving EFV-based regimens showed significant improvements comparable to children receiving NVP-based regimens. EFV-based regimens should be considered for young HIV-infected children co-infected with tuberculosis in resource-limited settings

Probing partially localized supergravity background of fundamental string ending on Dp-brane

We study the dynamics of the probe fundamental string in the field background of the partially localized supergravity solution for the fundamental string ending on Dp-brane. We separately analyze the probe dynamics for its motion along the worldvolume direction and the transverse direction of the source Dp-brane. We compare the dynamics of the probe along the Dp-brane worldvolume direction to the BIon dynamics.Comment: 20 pages, LaTeX, revised version to appear in Phys. Rev.

Noncommutative Differential Calculus for D-brane in Non-Constant B Field Background

In this paper we try to construct noncommutative Yang-Mills theory for generic Poisson manifolds. It turns out that the noncommutative differential calculus defined in an old work is exactly what we need. Using this calculus, we generalize results about the Seiberg-Witten map, the Dirac-Born-Infeld action, the matrix model and the open string quantization for constant B field to non-constant background with H=0.Comment: 21 pages, Latex file, references added, minor modificatio

Scattered Results in 2D String Theory

The nonperturbative $1\to N$ tachyon scattering amplitude in 2D type 0A string theory is computed. The probability that $N$ particles are produced is a monotonically decreasing function of $N$ whenever $N$ is large enough that statistical methods apply. The results are compared with expectations from black hole thermodynamics.Comment: 22 pages, 5 figures, harvmac. v2: minor comments added, typos correcte

Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness

BACKGROUND: There are conflicting data on the effects of antipsychotic medications on delirium in patients in the intensive care unit (ICU). METHODS: In a randomized, double-blind, placebo-controlled trial, we assigned patients with acute respiratory failure or shock and hypoactive or hyperactive delirium to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo. The volume and dose of a trial drug or placebo was halved or doubled at 12-hour intervals on the basis of the presence or absence of delirium, as detected with the use of the Confusion Assessment Method for the ICU, and of side effects of the intervention. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. Secondary end points included 30-day and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge. Safety end points included extrapyramidal symptoms and excessive sedation. RESULTS: Written informed consent was obtained from 1183 patients or their authorized representatives. Delirium developed in 566 patients (48%), of whom 89% had hypoactive delirium and 11% had hyperactive delirium. Of the 566 patients, 184 were randomly assigned to receive placebo, 192 to receive haloperidol, and 190 to receive ziprasidone. The median duration of exposure to a trial drug or placebo was 4 days (interquartile range, 3 to 7). The median number of days alive without delirium or coma was 8.5 (95% confidence interval [CI], 5.6 to 9.9) in the placebo group, 7.9 (95% CI, 4.4 to 9.6) in the haloperidol group, and 8.7 (95% CI, 5.9 to 10.0) in the ziprasidone group (P=0.26 for overall effect across trial groups). The use of haloperidol or ziprasidone, as compared with placebo, had no significant effect on the primary end point (odds ratios, 0.88 [95% CI, 0.64 to 1.21] and 1.04 [95% CI, 0.73 to 1.48], respectively). There were no significant between-group differences with respect to the secondary end points or the frequency of extrapyramidal symptoms. CONCLUSIONS: The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the ICU did not significantly alter the duration of delirium. (Funded by the National Institutes of Health and the VA Geriatric Research Education and Clinical Center; MIND-USA ClinicalTrials.gov number, NCT01211522 .)