Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

Joint evolution of dispersal and inbreeding load.

Inbreeding avoidance is often invoked to explain observed patterns of dispersal, and theoretical models indeed point to a possibly important role. However, while inbreeding load is usually assumed constant in these models, it is actually bound to vary dynamically under the combined influences of mutation, drift, and selection and thus to evolve jointly with dispersal. Here we report the results of individual-based stochastic simulations allowing such a joint evolution. We show that strongly deleterious mutations should play no significant role, owing to the low genomic mutation rate for such mutations. Mildly deleterious mutations, by contrast, may create enough heterosis to affect the evolution of dispersal as an inbreeding-avoidance mechanism, but only provided that they are also strongly recessive. If slightly recessive, they will spread among demes and accumulate at the metapopulation level, thus contributing to mutational load, but not to heterosis. The resulting loss of viability may then combine with demographic stochasticity to promote population fluctuations, which foster indirect incentives for dispersal. Our simulations suggest that, under biologically realistic parameter values, deleterious mutations have a limited impact on the evolution of dispersal, which on average exceeds by only one-third the values expected from kin-competition avoidance.

PPARbeta/delta regulates paneth cell differentiation via controlling the hedgehog signaling pathway.

BACKGROUND & AIMS: All 4 differentiated epithelial cell types found in the intestinal epithelium derive from the intestinal epithelial stem cells present in the crypt unit, in a process whose molecular clues are intensely scrutinized. Peroxisome proliferator-activated receptor beta (PPARbeta) is a nuclear hormone receptor activated by fatty acids and is highly expressed in the digestive tract. However, its function in intestinal epithelium homeostasis is understood poorly. METHODS: To assess the role of PPARbeta in the small intestinal epithelium, we combined various cellular and molecular approaches in wild-type and PPARbeta-mutant mice. RESULTS: We show that the expression of PPARbeta is particularly remarkable at the bottom of the crypt of the small intestine where Paneth cells reside. These cells, which have an important role in the innate immunity, are strikingly affected in PPARbeta-null mice. We then show that Indian hedgehog (Ihh) is a signal sent by mature Paneth cells to their precursors, negatively regulating their differentiation. Importantly, PPARbeta acts on Paneth cell homeostasis by down-regulating the expression of Ihh, an effect that can be mimicked by cyclopamine, a known inhibitor of the hedgehog signaling pathway. CONCLUSIONS: We unraveled the Ihh-dependent regulatory loop that controls mature Paneth cell homeostasis and its modulation by PPARbeta. PPARbeta currently is being assessed as a drug target for metabolic diseases; these results reveal some important clues with respect to the signals controlling epithelial cell fate in the small intestine.

Numerical simulation of gel electrophoresis of DNA knots in weak and strong electric fields.

Gel electrophoresis allows one to separate knotted DNA (nicked circular) of equal length according to the knot type. At low electric fields, complex knots, being more compact, drift faster than simpler knots. Recent experiments have shown that the drift velocity dependence on the knot type is inverted when changing from low to high electric fields. We present a computer simulation on a lattice of a closed, knotted, charged DNA chain drifting in an external electric field in a topologically restricted medium. Using a Monte Carlo algorithm, the dependence of the electrophoretic migration of the DNA molecules on the knot type and on the electric field intensity is investigated. The results are in qualitative and quantitative agreement with electrophoretic experiments done under conditions of low and high electric fields.

Daytime sleepiness with and without cataplexy in Chinese-Taiwanese patients.

BACKGROUND AND PURPOSE: Investigation of Chinese-Taiwanese patients with excessive sleepiness, but no association with other sleep disorders, and with the presence or absence of cataplexy. PATIENTS AND METHODS: Thirty-five patients, successively referred between 2002 and 2004, underwent polysomnography (PSG), repeat multiple sleep latency test (MSLT), and human leukocyte antigen (HLA) typing. Three patients without cataplexy also had cerebrospinal fluid (CSF) hypocretin measurements. RESULTS: DQB1*0602 was associated with cataplexy in over 90% of Chinese-Taiwanese cases. Absence of cataplexy and <2 sleep-onset REM periods (SOREMPs) was seen in only two subjects, but presence of two SOREMPs did not dissociate DQB1*0602 positive and negative or cataplexy positive and negative subjects. As a group, narcoleptics with cataplexy had a higher number of SOREMPs, and the mean sleep latency was much shorter in narcoleptics with cataplexy than in the non-cataplectic patients, independent of the number of SOREMPs. CONCLUSIONS: Chinese-Taiwanese patients with cataplexy present with similar HLA findings as Black and Caucasian patients, but the presence of two or more SOREMPs in Chinese-Taiwanese patients is not a sufficient diagnostic tool to identify narcolepsy. When cataplexy is not present, description of PSG nd HLA findings may be a better approach than using a label with little scientific significance, allowing for better collection of patients' phenotype.

Maintenance therapy with thalidomide improves survival in patients with multiple myeloma.

Newer chemotherapeutic protocols as well as high-dose chemotherapy have increased the response rate in myeloma. However, these treatments are not curative. Effective maintenance strategies are now required to prolong the duration of response. We conducted a randomized trial of maintenance treatment with thalidomide and pamidronate. Two months after high-dose therapy, 597 patients younger than age 65 years were randomly assigned to receive no maintenance (arm A), pamidronate (arm B), or pamidronate plus thalidomide (arm C). A complete or very good partial response was achieved by 55% of patients in arm A, 57% in arm B, and 67% in arm C (P = .03). The 3-year postrandomization probability of event-free survival was 36% in arm A, 37% in arm B, and 52% in arm C (P < .009). The 4-year postdiagnosis probability of survival was 77% in arm A, 74% in arm B, and 87% in arm C (P < .04). The proportion of patients who had skeletal events was 24% in arm A, 21% in arm B, and 18% in arm C (P = .4). Thalidomide is an effective maintenance therapy in patients with multiple myeloma. Maintenance treatment with pamidronate does not decrease the incidence of bone events.

Le refus scolaire [School refusal]

Pediatrician are often questioned by school refusal which relies on a wide range of psychopathological features and necessitates specific approaches. This disabling condition remains underestimated and is still increasing. A poor prognosis associated with a prolonged school absence is the common hallmark of school refusals, regardless of its heterogeneity. Its seriousness warrants early identification and prompt intervention by childhood healthcare professionals, teachers and social workers. A specialized treatment is needed, closely linked with families and school. Promising developments come from a functional rather than symptomatic concept of school refusal. They offer tailored interventions which fit the clinical diversity of school refusals. After a brief historical summary and current definitions of school refusal, the authors review the main clinical features and comorbidity before taking up treatment modalities.

"Lapsista lukeminen alkaa". Lastenkirjallisuuskritiikkien lapsuuskäsitykset 1960-1970-luvun vaihteessa

Analysoin tutkielmassani lapsuuskäsityksiä 1960-1970-luvun vaihteen lastenkirjakritiikeissä. Lähdeaineistona ovat pääasiassa Helsingin Sanomien, Arvostelevan kirjaluettelon ja Lapsi ja nuoriso -lehden arviot. Suhteutan kritiikkiaineiston myös lehdistössä käytyyn keskusteluun. Koska tutkin lehdistössä käytyä keskustelua, metodini on lähellä diskurssianalyysia. Käytän Michel Foucault’n diskurssianalyysiä tutkielman lähtökohtana, mutta en pyri kuitenkaan selvittämään syvällisesti diskurssien välisiä valtasuhteita tai diskurssiin pääsemättömiä näkökulmia. Diskurssi on tutkielmassani lehdistökeskustelun tai -kritiikin synonyymi. Tutkin, miten kriitikot merkityksellistävät lapsuutta 1960-1970-luvun vaihteen lastenkirjakritiikeissä. Pohdin myös ketkä toimivat lastenkirjakriitikkoina, mutta en lähde selvittämään tarkasti arvioijien taustoja. Suomalainen yhteiskunta oli 1960-1970-luvun vaihteessa erityisessä murrosvaiheessa. Hyvinvointivaltiota kehitettiin, väestö kaupungistui ja palkkatason kohotessa kulutus lisääntyi. Kulttuuripoliittinen keskustelu oli vireää ja vasemmistolaissävyiset ajatukset olivat konkreettisesti esillä. Lisäksi tarkastelen tutkielmassani sitä, näkyykö kritiikeissä kulttuurinen muutos. Suuri osa kirjoittajista oli kirjastoalan toimijoita, mutta Helsingin Sanomissa kriitikoina toimivat esimerkiksi myös taiteenalan asiantuntijat. Erityisenä kirjoittajaryhmänä toimivat myös lapset, jotka saivat tasa-arvon nimissä tuoda 1970-luvun alussa mielipiteensä esille omissa kirja-arvioinneissaan. Lastenkirjakritiikkien lapsuuskäsitykset ovat selkeässä yhteydessä muuhun yhteiskunnassa käytyyn keskusteluun. Lapset nähtiin kritiikeissä modernin kaupunkiyhteiskunnan rakentajina ja hyvinvointiyhteiskunnan toimijoina. Uuden sukupolven lapsen tuli sopeutua kriitikoiden näkökulmasta tulevaisuudessa heterogeeniseen kaupunkiyhteiskuntaan, hänen toivottiin ymmärtävän erilaisuutta ja osallistuvan kansainväliseen yhteistyöhön. Lapsen piti varautua tulevaisuuden ennustamattomuuteen, ristiriitaisuuksien kohtaamiseen, jatkuvaan kouluttautumiseen ja lisääntyneen informaation vastaanottamiseen. Kriitikoiden mielestä realistiset ja tietopohjaiset lastenkirjat olivat sopeuttamassa lasta jo nuorena yhteiskunnan jatkuvaan muutokseen. Lapsi nähtiin kritiikeissä myös ajattelevana ja vapaana yksilönä, jolla on oikeus ja mahdollisuudet tulla kuuluksi, tehdä valintoja ja itsenäisiä päätöksiä. Useat kriitikot huomioivat toisaalta myös uuteen kaupunkilaiseen yhteiskuntaan liittyvät vapaa-ajan ja populaarin viihteen leviämisen ongelmat. Lapsilta toivottiin jopa vasemmistokriittisiä kannanottoja kirja-arvioinneissaan ja muissa kirjoituksissaan. Pelkästä viihteen kulutuksesta intoutuneet lapset tuli kriitikoiden taholta ohjata heitä sivistävän ja heidän ajatuksiaan kehittävän kirjallisuuden pariin.

A global marine sedimentary response to the end-Permian mass extinction: Examples from southern Turkey and the western United States

The end-Permian mass extinction greatly diminished marine diversity and brought about a whole-scale restructuring of marine ecosystems; these ecosystem changes also profoundly affected the sedimentary record. Data presented here, attained through facies analyses of strata deposited during the immediate aftermath of the end-Permian mass extinction (southern Turkey) and at the close of the Early Triassic (southwestern United States), in combination with a literature review, show that sedimentary systems were profoundly affected by: (1) a reduction in biotic diversity and abundance and (2) long-term environmental fluctuations that resulted from the end-Permian crisis. Lower Triassic strata display widespread microbialite and carbonate seafloor fan development and contain indicators of suppressed infaunal bioturbation such as flat-pebble conglomerates and wrinkle structures (facies considered unusual in post-Cambrian subtidal deposits). Our observations suggest that depositional systems, too, respond to biotic crises, and that certain facies may act as barometers of ecologic and environmental change independent of fossil assemblage analyses. Close investigation of facies changes during other critical times in Earth history may serve as an important tool in interpreting the ecology of metazoans and their environment.

Deoxyribonucleic acid content as an indicator of progression of squamous cell carcinogenesis in the esophagus: comparative analysis on imprint-cytospin and tissue section preparation.

BACKGROUND: The purpose of this study was to explore the potential use of image analysis on tissue sections preparation as a predictive marker of early malignant changes during squamous cell (SC) carcinogenesis in the esophagus. Results of DNA ploidy quantification on formalin-fixed, paraffin-embedded tissue using two different techniques were compared: imprint-cytospin and 6 microm thick tissue sections preparation. METHODS: This retrospective study included 26 surgical specimens of squamous cell carcinoma (SCC) from patients who underwent surgery alone at the Department of Surgery in CHUV Hospital in Lausanne between January 1993 and December 2000. We analyzed 53 samples of healthy tissue, 43 tumors and 7 lymph node metastases. RESULTS: Diploid DNA histogram patterns were observed in all histologically healthy tissues, either distant or proximal to the lesion. Aneuploidy was observed in 34 (79%) of 43 carcinomas, namely 24 (75%) of 32 early squamous cell carcinomas and 10 (91%) of 11 advanced carcinomas. DNA content was similar in the different tumor stages, whether patients presented with single or multiple synchronous tumors. All lymph node metastases had similar DNA content as their primary tumor. CONCLUSIONS: Early malignant changes in the esophagus are associated with alteration in DNA content, and aneuploidy tends to correlate with progression of invasive SCC. A very good correlation between imprint-cytospin and tissue section analysis was observed. Although each method used here showed advantages and disadvantages; tissue sections preparation provided useful information on aberrant cell-cycle regulation and helped select the optimal treatment for the individual patient along with consideration of other clinical parameters.

Early effects of intravitreal triamcinolone on macular edema: mechanistic implication.

PURPOSE: To evaluate the early effects of intravitreal triamcinolone acetonide (TA) on cystoid macular edema associated with retinal vein occlusion and diabetic retinopathy. DESIGN: Prospective, interventional, small case series. PARTICIPANTS: Four patients with cystoid macular edema resulting from retinal vein occlusion or diabetic retinopathy of more than 4 months' duration and evaluated as suitable for treatment with intravitreous injection of TA. METHODS: After ophthalmic examination, including visual acuity assessment, intraocular pressure (IOP) measurement, and optical coherence tomography (OCT) analysis, the patients received a single intravitreal injection of 4 mg TA. After the injection, consecutive visual acuity assessment, IOP measurement, and OCT analysis were performed after 1 hour, 6 hours, 1 week, and 2 weeks. MAIN OUTCOME MEASURE: Optical coherence tomography assessment of macular thickness. RESULTS: Macular thickness and edema initially were reduced as early as 1 hour after TA injection. A further continuous decrease was observed during the 2 weeks after treatment. CONCLUSIONS: This rapid effect of intravitreal TA is interpreted to indicate that nongenomic effects on retinal or retinal pigment epithelial cell membranes, or both, may be responsible for this phenomenon. Identifications of these mechanisms may help design alternative, more specific drugs for the treatment of macular edema.

Dinâmica da água nas palhadas de milho, milheto e soja utilizadas em plantio direto

O objetivo deste trabalho foi avaliar o efeito das palhadas de milho, milheto e soja na capacidade de interceptação e de armazenamento de água, velocidade de dessecamento, porcentagem de cobertura do solo, interceptação da radiação solar e escoamento superficial, assim como incorporar estes efeitos em um modelo de crescimento de plantas. As palhadas de milheto e de milho apresentaram capacidade maior de armazenar água do que a de soja: 3,26, 3,24 e 2,62 g de água por grama de palhada, respectivamente. A quantidade de água perdida pelos resíduos foi proporcional à evapotranspiração potencial. As taxas de cobertura foram equivalentes nos três tipos de material. Os três tipos de palhada foram similares na interceptação das radiações fotossinteticamente ativa e infravermelha. Os resíduos do milheto foram eficientes no controle do escoamento superficial: do total de 843,5 mm de água precipitada, apenas 45,5 mm foram perdidos pelo escoamento superficial no sistema de plantio direto enquanto no convencional as perdas de água foram de 222,5 mm. Os modelos linear e exponencial expressam de forma significativa a maior parte das relações estudadas.

Caracterização bioquímica de linhagens de soja com alto teor de proteína

O objetivo deste trabalho foi caracterizar bioquimicamente duas isolinhas de soja com alto teor de proteína. O aumento do teor de proteína nas isolinhas foi acompanhado por redução no teor de óleo e de carboidratos totais. Em relação à composição aminoacídica, o aumento do teor de proteína promoveu acréscimo em todos os aminoácidos, exceto glicina, alanina, metionina, cisteína e tirosina, mantendo a relação enxofre/nitrogênio. A quantificação dos polipeptídios mostrou que o aumento do teor de proteína manteve inalterado o teor das proteínas 7S, promoveu aumento no teor das proteínas 11S e, conseqüentemente, da relação 11S/7S. Pode haver melhoria na qualidade do farelo de soja das isolinhas, uma vez que as proteínas 11S têm melhor qualidade nutricional do que as proteínas 7S.

Dados climáticos simulados e produtividade potencial do milho

O objetivo deste trabalho foi avaliar uma metodologia para estimar a produtividade potencial da cultura do milho de acordo com valores médios diários de temperatura do ar e radiação solar, utilizando procedimento estocástico. Valores registrados da temperatura média diária do ar durante 86 anos e da radiação solar global diária durante 25 anos, foram fornecidos pela Estação Agrometeorológica de Piracicaba (Esalq/USP). Valores correspondentes à produtividade potencial foram simulados 1.000 vezes, em cada data de semeadura considerada (15/10 - época normal; 15/2 - safrinha; e 15/8 - safra de inverno). Foram considerados dois casos na distribuição de probabilidade normal truncada (valores extremos: média - 1,96 desvio-padrão e média + 1,96 desvio-padrão): temperatura média diária variável e radiação solar global diária constante, e temperatura média diária constante e radiação solar global diária variável. A metodologia de estimação permite definir a ordem de grandeza da produtividade potencial de milho a determinada localidade, com base nos dados de temperatura e radiação solar. O procedimento estocástico proposto permite associar a produtividade potencial de milho a determinada probabilidade.