Secrets of Light: Notes on an Exposed Anthropology

Strongly inspired by the mysterious exercise of recording, protecting, and revealing the images in Luis Poirot’s photographic archive, this article experiments with a mode of ethnographic writing that, rather than trying to convince the reader about the correctness of its conceptual propositions, it simply suggests certain secrets of light. These are images appearing in multiple temporalities as vivid evidence of the presence of absences. Attempting to avoid the sterilization of ‘lived experience’ and its multiple temporalities, often produced by the anthropological discipline itself, this article imagines an exposed anthropology. Rather than being interested in the creation and analysis of concepts, this exposed anthropology focuses on opening up suggestive spaces of coexistence with the presence of absence. Thus, it offers singular evidence of the encounter of worlds occurring beyond concepts. In particular, this work gives an account of how Poirot’s photographic archive, and the present absences that inhabit his images affect, resonate and even incorporate the ethnographic writing itself within the same living archive.ResumenFuertemente inspirado por el misterioso ejercicio que supone registrar, proteger y revelar las imágenes del archivo fotográfico de Luis Poirot, este trabajo experimenta con un modo de escribir etnográficamente que, más que intentar convencer al lector sobre lo adecuado de sus proposiciones conceptuales, simplemente sugiere secretos de luz, imágenes que aparecen en temporalidades múltiples como evidencia viva de la presencia de la ausencia. Intentando evitar la esterilización de la experiencia vivida y sus múltiples temporalidades, muchas veces producida por la misma disciplina antropológica, este trabajo imagina una antropología expuesta que, más que interesarse en el análisis y creación de conceptos, se aboca a abrir espacios sugestivos de coexistencia con la presencia de la ausencia y ofrecer una evidencia singular del encuentro entre mundos que, al tocarse, van más allá de lo conceptual. En particular, este trabajo da cuenta de cómo el archivo fotográfico de Poirot y las ausencias presentes que habitan sus imágenes, afectan, resuenan y hasta incorporan la propia escritura etnográfica dentro del mismo archivo vivo.<br/

TALEN-Mediated Inactivation of PD-1 in Tumor-Reactive Lymphocytes Promotes Intratumoral T-cell Persistence and Rejection of Established Tumors

Despite the promising efficacy of adoptive cell therapies (ACT) in melanoma, complete response rates remain relatively low and outcomes in other cancers are less impressive. The immunosuppressive nature of the tumor microenvironment and the expression of immune-inhibitory ligands, such as PD-L1/CD274 by the tumor and stroma are considered key factors limiting efficacy. The addition of checkpoint inhibitors (CPI) to ACT protocols bypasses some mechanisms of immunosuppression, but associated toxicities remain a significant concern. To overcome PD-L1–mediated immunosuppression and reduce CPI-associated toxicities, we used TALEN technology to render tumor-reactive T cells resistant to PD-1 signaling. Here, we demonstrate that inactivation of the PD-1 gene in melanoma-reactive CD8+ T cells and in fibrosarcoma-reactive polyclonal T cells enhanced the persistence of PD-1 gene-modified T cells at the tumor site and increased tumor control. These results illustrate the feasibility and potency of approaches incorporating advanced gene-editing technologies into ACT protocols to silence immune checkpoints as a strategy to overcome locally active immune escape pathways

Age-Appropriate Feeding Practices in Cambodia and the Possible Influence on the Growth of the Children:A Longitudinal Study

Age-appropriate feeding practice (ADF) during early childhood are vital for optimal nutrition. This longitudinal study determined the effect of selected risk factors and ADF, as described by the National Nutritional Recommendations, on linear and ponderal growth of children below 24 months of age. Weight and length measures were used to calculate z-scores of anthropometric measures by WHO standards. The prevalence of stunting increased from 13.2% to 32.4% over time, while prevalence of wasting remained stable (14.5%). At first visit, 43% of children of all ages complied with ADF criteria, a proportion which decreased to 7.1% in follow-up. The quality of feeding practices for children above 12 months of age was the poorest, where at the last visit, only 6% complied with the criteria for ADF. The linear mixed-effect models found the association between ADF and ponderal growth to be significant (weight-for-height estimate: 0.05 SD). In Cambodia, Ratanakiri province, ADF was the second largest determinant for ponderal growth. We recommend province specific public health actions. For children above 6 months, the quantity of food given needs to be increased, followed by the meal frequency. Mothers&rsquo; educational level, improved sanitation, and drinking water quality were among strongest predictors of a child&rsquo;s growth

Signature of stripe pinning in optical conductivity

The response of charge stripes to an external electric field applied perpendicular to the stripe direction is studied within a diagrammatic approach for both weak and strong pinning by random impurities. The sound-like mode of the stripes described as elastic strings moves to finite frequency due to impurity pinning. By calculating the optical conductivity we determine this characteristic energy scale for both a single stripe and an array of interacting stripes. The results explain the anomalous far-infrared peak observed recently in optical-conductivity measurements on cuprates.Comment: Revised version, to appear in Phys. Rev.

The motor function measure to study limitation of activity in children and adults with Charcot-Marie-Tooth disease

AbstractObjectiveTo study the applicability and responsiveness of the motor function measure (total score and sub-scores D1, D2 and D3) in patients with Charcot-Marie-Tooth disease.Patients and methodsTwo hundred and thirty-three patients aged 4–86 years were included in the descriptive study. Scores and sub-scores were analyzed by age and by disease subtypes. Sensitivity to change (responsiveness) was estimated in patients having had at least two evaluations with at least six months between the first and the second.ResultsMotor function measure scores decrease with age, especially sub-scores D1 and D3. There were no significant differences between the scores according to type of Charcot-Marie-Tooth disease. The scores were significantly higher for ambulatory than for non-ambulatory patients. Significant responsiveness was demonstrated only in type 2 Charcot-Marie-Tooth disease.Discussion/conclusionsOur results suggest that, especially for D1 and D3 sub-scores, the motor function measure is a reliable and valid outcome measure that can be usefully applied in longitudinal follow-up. Studies of longer duration could demonstrate its responsiveness in other Charcot-Marie-Tooth disease subtypes

Gene editing of PKLR gene in human hematopoietic progenitors through 5' and 3' UTR modified TALEN mRNA

Pyruvate Kinase Deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene, which encodes the erythroid specific Pyruvate Kinase enzyme. Erythrocytes from PKD patients show an energetic imbalance and are susceptible to hemolysis. Gene editing of hematopoietic stem cells (HSCs) would provide a therapeutic benefit and improve safety of gene therapy approaches to treat PKD patients. In previous studies, we established a gene editing protocol that corrected the PKD phenotype of PKD-iPSC lines through a TALEN mediated homologous recombination strategy. With the goal of moving toward more clinically relevant stem cells, we aim at editing the PKLR gene in primary human hematopoietic progenitors and hematopoietic stem cells (HPSCs). After nucleofection of the gene editing tools and selection with puromycin, up to 96% colony forming units showed precise integration. However, a low yield of gene edited HPSCs was associated to the procedure. To reduce toxicity while increasing efficacy, we worked on i) optimizing gene editing tools and ii) defining optimal expansion and selection times. Different versions of specific nucleases (TALEN and CRISPR-Cas9) were compared. TALEN mRNAs with 5' and 3' added motifs to increase RNA stability were the most efficient nucleases to obtain high gene editing frequency and low toxicity. Shortening ex vivo manipulation did not reduce the efficiency of homologous recombination and preserved the hematopoietic progenitor potential of the nucleofected HPSCs. Lastly, a very low level of gene edited HPSCs were detected after engraftment in immunodeficient (NSG) mice. Overall, we showed that gene editing of the PKLR gene in HPSCs is feasible, although further improvements must to be done before the clinical use of the gene editing to correct PKD. Institutode Investigacio ' n Sanitaria de la Fundacio '

Gene editing of PKLR gene in human hematopoietic progenitors through 5' and 3' UTR modified TALEN mRNA

TheauthorswouldliketothankMiguelA.MartinforthecarefulmaintenanceofNSGmice,andRebecaSa ́nchezandOmairaAlberquillafortheirtechnicalassistanceinflowcytometry.TheauthorsalsothankFundacio ́n Botı ́n forpromotingtranslationalresearchattheHemato-poieticInnovativeTherapiesDivisionoftheCIEMATPyruvate Kinase Deficiency (PKD) is a rare erythroid metabolic disease caused by mutations in the PKLR gene, which encodes the erythroid specific Pyruvate Kinase enzyme. Erythrocytes from PKD patients show an energetic imbalance and are susceptible to hemolysis. Gene editing of hematopoietic stem cells (HSCs) would provide a therapeutic benefit and improve safety of gene therapy approaches to treat PKD patients. In previous studies, we established a gene editing protocol that corrected the PKD phenotype of PKD-iPSC lines through a TALEN mediated homologous recombination strategy. With the goal of moving toward more clinically relevant stem cells, we aim at editing the PKLR gene in primary human hematopoietic progenitors and hematopoietic stem cells (HPSCs). After nucleofection of the gene editing tools and selection with puromycin, up to 96% colony forming units showed precise integration. However, a low yield of gene edited HPSCs was associated to the procedure. To reduce toxicity while increasing efficacy, we worked on i) optimizing gene editing tools and ii) defining optimal expansion and selection times. Different versions of specific nucleases (TALEN and CRISPR-Cas9) were compared. TALEN mRNAs with 5' and 3' added motifs to increase RNA stability were the most efficient nucleases to obtain high gene editing frequency and low toxicity. Shortening ex vivo manipulation did not reduce the efficiency of homologous recombination and preserved the hematopoietic progenitor potential of the nucleofected HPSCs. Lastly, a very low level of gene edited HPSCs were detected after engraftment in immunodeficient (NSG) mice. Overall, we showed that gene editing of the PKLR gene in HPSCs is feasible, although further improvements must to be done before the clinical use of the gene editing to correct PKD.S

International Expert Opinions and Recommendations on the Use of Melatonin in the Treatment of Insomnia and Circadian Sleep Disturbances in Adult Neuropsychiatric Disorders

Introduction: Insomnia and circadian rhythm disorders, such as the delayed sleep phase syndrome, are frequent in psychiatric disorders and their evaluation and management in early stages should be a priority. The aim of this paper was to express recommendations on the use of exogenous melatonin, which exhibits both chronobiotic and sleep-promoting actions, for the treatment of these sleep disturbances in psychiatric disorders. Methods: To this aim, we conducted a systematic review according to PRISMA on the use of melatonin for the treatment of insomnia and circadian sleep disorders in neuropsychiatry. We expressed recommendations for the use of melatonin in psychiatric clinical practice for each disorder using the RAND/UCLA appropriateness method. Results: We selected 41 studies, which included mood disorders, schizophrenia, substance use disorders, attention deficit hyperactivity disorders, autism spectrum disorders, neurocognitive disorders, and delirium; no studies were found for both anxiety and eating disorders. Conclusion: The administration of prolonged release melatonin at 2–10 mg, 1–2 h before bedtime, might be used in the treatment of insomnia symptoms or comorbid insomnia in mood disorders, schizophrenia, in adults with autism spectrum disorders, neurocognitive disorders and during sedative-hypnotics discontinuation. Immediate release melatonin at &lt;1 mg might be useful in the treatment of circadian sleep disturbances of neuropsychiatric disorders

PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery

We have developed PVS (Protein Variability Server), a web-based tool that uses several variability metrics to compute the absolute site variability in multiple protein-sequence alignments (MSAs). The variability is then assigned to a user-selected reference sequence consisting of either the first sequence in the alignment or a consensus sequence. Subsequently, PVS performs tasks that are relevant for structure-function studies, such as plotting and visualizing the variability in a relevant 3D-structure. Neatly, PVS also implements some other tasks that are thought to facilitate the design of epitope discovery-driven vaccines against pathogens where sequence variability largely contributes to immune evasion. Thus, PVS can return the conserved fragments in the MSA—as defined by a user-provided variability threshold—and locate them in a relevant 3D-structure. Furthermore, PVS can return a variability-masked sequence, which can be directly submitted to the RANKPEP server for the prediction of conserved T-cell epitopes. PVS is freely available at: http://imed.med.ucm.es/PVS/

Mid-Infrared Conductivity from Mid-Gap States Associated with Charge Stripes

The optical conductivity of La(2-x)Sr(x)NiO(4) has been interpreted in various ways, but so far the proposed interpretations have neglected the fact that the holes doped into the NiO(2) planes order in diagonal stripes, as established by neutron and X-ray scattering. Here we present a study of optical conductivity in La(2)NiO(4+d) with d=2/15, a material in which the charge stripes order three-dimensionally. We show that the conductivity can be decomposed into two components, a mid-infrared peak that we attribute to transitions from the filled valence band into empty mid-gap states associated with the stripes, and a Drude peak that appears at higher temperatures as carriers are thermally excited into the mid-gap states. The shift of the mid-IR peak to lower energy with increasing temperature is explained in terms of the Franck-Condon effect. The relevance of these results to understanding the optical conductivity in the cuprates is discussed.Comment: final version of paper (minor changes from previous version