Guide to archiving personal data

Key messages in this Guide: -Data Protection law shapes archiving of personal data. It supports it and does not prevent it; -Personal data worthy of permanent preservation should be safeguarded by recordkeepers until it is archived; - The new archiving in the public interest purpose adapts the operation of various principles and maintains exemptions from data subject rights such as the right to be forgotten and data rectification where the necessary safeguards are met

Macrophage CD74 contributes to MIF-induced pulmonary inflammation

<p>Abstract</p> <p>Background</p> <p>MIF is a critical mediator of the host defense, and is involved in both acute and chronic responses in the lung. Neutralization of MIF reduces neutrophil accumulation into the lung in animal models. We hypothesized that MIF, in the alveolar space, promotes neutrophil accumulation via activation of the CD74 receptor on macrophages.</p> <p>Methods</p> <p>To determine whether macrophage CD74 surface expression contributes MIF-induced neutrophil accumulation, we instilled recombinant MIF (r-MIF) into the trachea of mice in the presence or absence of anti-CD74 antibody or the MIF specific inhibitor, ISO-1. Using macrophage culture, we examined the downstream pathways of MIF-induced activation that lead to neutrophil accumulation.</p> <p>Results</p> <p>Intratracheal instillation of r-MIF increased the number of neutrophils as well as the concentration of macrophage inflammatory protein 2 (MIP-2) and keratinocyte-derived chemokine (KC) in BAL fluids. CD74 was found to be expressed on the surface of alveolar macrophages, and MIF-induced MIP-2 accumulation was dependent on p44/p42 MAPK in macrophages. Anti-CD74 antibody inhibited MIF-induced p44/p42 MAPK phosphorylation and MIP-2 release by macrophages. Furthermore, we show that anti-CD74 antibody inhibits MIF-induced alveolar accumulation of MIP-2 (control IgG vs. CD74 Ab; 477.1 ± 136.7 vs. 242.2 ± 102.2 pg/ml, p < 0.05), KC (1796.2 ± 436.1 vs. 1138.2 ± 310.2 pg/ml, p < 0.05) and neutrophils (total number of neutrophils, 3.33 ± 0.93 × 10⁴vs. 1.90 ± 0.61 × 10⁴, p < 0.05) in our mouse model.</p> <p>Conclusion</p> <p>MIF-induced neutrophil accumulation in the alveolar space results from interaction with CD74 expressed on the surface of alveolar macrophage cells. This interaction induces p44/p42 MAPK activation and chemokine release. The data suggest that MIF and its receptor, CD74, may be useful targets to reduce neutrophilic lung inflammation, and acute lung injury.</p

The translation of cell-based therapies:clinical landscape and manufacturing challenges

Cell-based therapies have the potential to make a large contribution toward currently unmet patient need and thus effective manufacture of these products is essential. Many challenges must be overcome before this can become a reality and a better definition of the manufacturing requirements for cell-based products must be obtained. The aim of this study is to inform industry and academia of current cell-based therapy clinical development and to identify gaps in their manufacturing requirements. A total of 1342 active cell-based therapy clinical trials have been identified and characterized based on cell type, target indication and trial phase. Multiple technologies have been assessed for the manufacture of these cell types in order to facilitate product translation and future process development

Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth

Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations

The impact of cumulative obstetric complications and childhood trauma on brain volume in young people with psychotic experiences

Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders

Cue-Reactors: Individual Differences in Cue-Induced Craving after Food or Smoking Abstinence

Background: Pavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues? Methods: We examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating. Results: Certain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving. Conclusions: In humans, like in nonhumans, there may be a ‘‘cue-reactive’ ’ phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking cessation

Feasibility study of an internally cooled bipolar applicator for RF coagulation of hepatic tissue: Experimental and computational study

Purpose: To study the capacity of an internally cooled radiofrequency (RF) bipolar applicator to create sufficiently deep thermal lesions in hepatic tissue. Materials and methods: Three complementary methodologies were employed to check the electrical and thermal behaviour of the applicator under test. The experimental studies were based on excised bovine (ex vivo study) and porcine liver (in vivo study) and the theoretical models were solved by means of the finite element method (FEM). Results: Experimental and computational results showed good agreement in terms of impedance progress and lesion depth (4 and 4.5 mm respectively for ex vivo conditions, and approximately 7 and 9 mm respectively for in vivo conditions), although the lesion widths were overestimated by the computer simulations. This could have been due to the method used to assess the thermal lesions; the experimental lesions were assessed by the white coagulation zone, whereas the tissue damage function was used to assess the computational lesions. Conclusions: The experimental results suggest that this applicator could create in vivo lesions to a depth of around 7mm. It was also observed that the thermal lesion is mainly confined to the area between both electrodes, which would allow lesion width to be controlled by selecting a specific applicator design. The comparison between the experimental and computational results suggests that the theoretical model could be usefully applied in further studies of the performance of this device. © 2012 Informa UK Ltd All rights reserved.This work received financial support from the Spanish Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion TEC2011-27133-C02-(01 and 02), from Universitat Politecnica de Valencia (INNOVA11-01-5502; and PAID-06-11 Ref. 1988). A. Gonzalez-Suarez is the recipient of grant VaLi+D (ACIF/2011/194) from the Generalitat Valenciana. The proof-reading of this paper was funded by the Universitat Politecnica de Valencia, Spain. The authors alone are responsible for the content and writing of the paper.González Suárez, A.; Trujillo Guillen, M.; Burdío Pinilla, F.; Andaluz Martínez, AM.; Berjano Zanón, E. (2012). Feasibility study of an internally cooled bipolar applicator for RF coagulation of hepatic tissue: Experimental and computational study. International Journal of Hyperthermia. 28(7):663-673. https://doi.org/10.3109/02656736.2012.716900S663673287Topp, S. A., McClurken, M., Lipson, D., Upadhya, G. A., Ritter, J. H., Linehan, D., & Strasberg, S. M. (2004). Saline-Linked Surface Radiofrequency Ablation. Annals of Surgery, 239(4), 518-527. doi:10.1097/01.sla.0000118927.83650.a4Gnerlich, J. L., Ritter, J. H., Linehan, D. C., Hawkins, W. G., & Strasberg, S. M. (2009). Saline-Linked Surface Radiofrequency Ablation. Annals of Surgery, 250(1), 96-102. doi:10.1097/sla.0b013e3181ae91afSakamoto, Y., Yamamoto, J., Kokudo, N., Seki, M., Kosuge, T., Yamaguchi, T., … Makuuchi, M. (2004). Bloodless liver resection using the Monopolar Floating Ball plus Ligasure diathermy: Preliminary results of 16 liver resections. World Journal of Surgery, 28(2), 166-172. doi:10.1007/s00268-003-7167-5Poon, R. T., Fan, S. T., & Wong, J. (2005). Liver resection using a saline-linked radiofrequency dissecting sealer for transection of the liver. Journal of the American College of Surgeons, 200(2), 308-313. doi:10.1016/j.jamcollsurg.2004.10.008EVERETT IV, T. H., LEE, K. W., WILSON, E. E., GUERRA, J. M., VAROSY, P. D., & OLGIN, J. E. (2008). Safety Profiles and Lesion Size of Different Radiofrequency Ablation Technologies: A Comparison of Large Tip, Open and Closed Irrigation Catheters. Journal of Cardiovascular Electrophysiology, 20(3), 325-335. doi:10.1111/j.1540-8167.2008.01305.xYokoyama, K., Nakagawa, H., Wittkampf, F. H. M., Pitha, J. V., Lazzara, R., & Jackman, W. M. (2006). Comparison of Electrode Cooling Between Internal and Open Irrigation in Radiofrequency Ablation Lesion Depth and Incidence of Thrombus and Steam Pop. Circulation, 113(1), 11-19. doi:10.1161/circulationaha.105.540062Demazumder, D., Mirotznik, M. S., & Schwartzman, D. (2001). Journal of Interventional Cardiac Electrophysiology, 5(4), 391-400. doi:10.1023/a:1013241927388Cooper, J. M., Sapp, J. L., Tedrow, U., Pellegrini, C. P., Robinson, D., Epstein, L. M., & Stevenson, W. G. (2004). Ablation with an internally irrigated radiofrequency catheter: Learning how to avoid steam pops. Heart Rhythm, 1(3), 329-333. doi:10.1016/j.hrthm.2004.04.019Burdío, F., Grande, L., Berjano, E., Martinez-Serrano, M., Poves, I., Burdío, J. M., … Güemes, A. (2010). A new single-instrument technique for parenchyma division and hemostasis in liver resection: a clinical feasibility study. The American Journal of Surgery, 200(6), e75-e80. doi:10.1016/j.amjsurg.2010.02.020Ríos, J. S., Zalabardo, J. M. S., Burdio, F., Berjano, E., Moros, M., Gonzalez, A., … Güemes, A. (2011). Single Instrument for Hemostatic Control in Laparoscopic Partial Nephrectomy in a Porcine Model Without Renal Vascular Clamping. Journal of Endourology, 25(6), 1005-1011. doi:10.1089/end.2010.0557Dorcaratto, D., Burdío, F., Fondevila, D., Andaluz, A., Poves, I., Martinez, M. A., … Grande, L. (2012). Laparoscopic Distal Pancreatectomy: Feasibility Study of Radiofrequency-Assisted Transection in a Porcine Model. Journal of Laparoendoscopic & Advanced Surgical Techniques, 22(3), 242-248. doi:10.1089/lap.2011.0417Zeh, A., Messer, J., Davis, J., Vasarhelyi, A., & Wohlrab, D. (2010). The Aquamantys System—An Alternative To Reduce Blood Loss in Primary Total Hip Arthroplasty? The Journal of Arthroplasty, 25(7), 1072-1077. doi:10.1016/j.arth.2009.10.008Sprunger, J., & Herrell, S. D. (2005). Partial Laparoscopic Nephrectomy Using Monopolar Saline-Coupled Radiofrequency Device: Animal Model and Tissue Effect Characterization. Journal of Endourology, 19(4), 513-519. doi:10.1089/end.2005.19.513Voeller, R. K., Zierer, A., Lall, S. C., Sakamoto, S., Schuessler, R. B., & Damiano, R. J. (2010). Efficacy of a novel bipolar radiofrequency ablation device on the beating heart for atrial fibrillation ablation: A long-term porcine study. The Journal of Thoracic and Cardiovascular Surgery, 140(1), 203-208. doi:10.1016/j.jtcvs.2009.06.034Pai, M., Spalding, D., Jiao, L., & Habib, N. (2012). Use of Bipolar Radiofrequency in Parenchymal Transection of the Liver, Pancreas and Kidney. Digestive Surgery, 29(1), 43-47. doi:10.1159/000335732Berjano, E. J. (2006). BioMedical Engineering OnLine, 5(1), 24. doi:10.1186/1475-925x-5-24Tungjitkusolmun, S., Staelin, S. T., Haemmerich, D., Jang-Zern Tsai, Hong Cao, Webster, J. G., … Vorperian, V. R. (2002). Three-dimensional finite-element analyses for radio-frequency hepatic tumor ablation. IEEE Transactions on Biomedical Engineering, 49(1), 3-9. doi:10.1109/10.972834Doss, J. D. (1982). Calculation of electric fields in conductive media. Medical Physics, 9(4), 566-573. doi:10.1118/1.595107Abraham, J. P., & Sparrow, E. M. (2007). A thermal-ablation bioheat model including liquid-to-vapor phase change, pressure- and necrosis-dependent perfusion, and moisture-dependent properties. International Journal of Heat and Mass Transfer, 50(13-14), 2537-2544. doi:10.1016/j.ijheatmasstransfer.2006.11.045Jo, B., & Aksan, A. (2010). Prediction of the extent of thermal damage in the cornea during conductive keratoplasty. Journal of Thermal Biology, 35(4), 167-174. doi:10.1016/j.jtherbio.2010.02.004Pearce, J., Panescu, D., & Thomsen, S. (2005). Simulation of diopter changes in radio frequency conductive keratoplasty in the cornea. Modelling in Medicine and Biology VI. doi:10.2495/bio050451Yang, D., Converse, M. C., Mahvi, D. M., & Webster, J. G. (2007). Expanding the Bioheat Equation to Include Tissue Internal Water Evaporation During Heating. IEEE Transactions on Biomedical Engineering, 54(8), 1382-1388. doi:10.1109/tbme.2007.890740Zhao, G., Zhang, H.-F., Guo, X.-J., Luo, D.-W., & Gao, D.-Y. (2007). Effect of blood flow and metabolism on multidimensional heat transfer during cryosurgery. Medical Engineering & Physics, 29(2), 205-215. doi:10.1016/j.medengphy.2006.03.005Pätz T, Körger T, Preusser T, Simulation of radiofrequency ablation including water evaporation. In: IFMBE Proceedings of the World Congress on Medical Physics and Biomedical Engineering 25/IV, 2009, 1287–1290Berjano, E. J., Burdío, F., Navarro, A. C., Burdío, J. M., Güemes, A., Aldana, O., … Gregorio, M. A. de. (2006). Improved perfusion system for bipolar radiofrequency ablation of liver: preliminary findings from a computer modeling study. Physiological Measurement, 27(10), N55-N66. doi:10.1088/0967-3334/27/10/n03Burdío, F., Berjano, E. J., Navarro, A., Burdío, J. M., Grande, L., Gonzalez, A., … Lequerica, J. L. (2009). Research and development of a new RF-assisted device for bloodless rapid transection of the liver: Computational modeling and in vivo experiments. BioMedical Engineering OnLine, 8(1), 6. doi:10.1186/1475-925x-8-6Chang, I. A., & Nguyen, U. D. (2004). BioMedical Engineering OnLine, 3(1), 27. doi:10.1186/1475-925x-3-27Beop-Min Kim, Jacques, S. L., Rastegar, S., Thomsen, S., & Motamedi, M. (1996). Nonlinear finite-element analysis of the role of dynamic changes in blood perfusion and optical properties in laser coagulation of tissue. IEEE Journal of Selected Topics in Quantum Electronics, 2(4), 922-933. doi:10.1109/2944.577317Panescu, D., Whayne, J. G., Fleischman, S. D., Mirotznik, M. S., Swanson, D. K., & Webster, J. G. (1995). Three-dimensional finite element analysis of current density and temperature distributions during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 42(9), 879-890. doi:10.1109/10.412649González-Suárez A, Alba J, Trujillo M, Berjano E, Experimental and theoretical study of an internally cooled bipolar electrode for RF coagulation of biological tissues. Conf Proc IEEE Eng Med Biol Soc 2011;6878–6881Rosenberg, A. G. (2007). Reducing Blood Loss in Total Joint Surgery With a Saline-Coupled Bipolar Sealing Technology. The Journal of Arthroplasty, 22(4), 82-85. doi:10.1016/j.arth.2007.02.018PETERSEN, H. H., ROMAN-GONZALEZ, J., JOHNSON, S. B., HASTRUP SVENDSEN, J., HAUNSO, S., & PACKER, D. L. (2004). Mechanisms for Enlarging Lesion Size During Irrigated Tip Radiofrequency Ablation:. Is There a Virtual Electrode Effect? Journal of Interventional Cardiology, 17(3), 171-177. doi:10.1111/j.1540-8183.2004.09879.

Time separation as a hidden variable to the Copenhagen school of quantum mechanics

The Bohr radius is a space-like separation between the proton and electron in the hydrogen atom. According to the Copenhagen school of quantum mechanics, the proton is sitting in the absolute Lorentz frame. If this hydrogen atom is observed from a different Lorentz frame, there is a time-like separation linearly mixed with the Bohr radius. Indeed, the time-separation is one of the essential variables in high-energy hadronic physics where the hadron is a bound state of the quarks, while thoroughly hidden in the present form of quantum mechanics. It will be concluded that this variable is hidden in Feynman's rest of the universe. It is noted first that Feynman's Lorentz-invariant differential equation for the bound-state quarks has a set of solutions which describe all essential features of hadronic physics. These solutions explicitly depend on the time separation between the quarks. This set also forms the mathematical basis for two-mode squeezed states in quantum optics, where both photons are observable, but one of them can be treated a variable hidden in the rest of the universe. The physics of this two-mode state can then be translated into the time-separation variable in the quark model. As in the case of the un-observed photon, the hidden time-separation variable manifests itself as an increase in entropy and uncertainty.Comment: LaTex 10 pages with 5 figure. Invited paper presented at the Conference on Advances in Quantum Theory (Vaxjo, Sweden, June 2010), to be published in one of the AIP Conference Proceedings serie

Physiological properties of enkephalin-containing neurons in the spinal dorsal horn visualized by expression of green fluorescent protein in BAC transgenic mice

<p>Abstract</p> <p>Background</p> <p>Enkephalins are endogenous opiates that are assumed to modulate nociceptive information by mediating synaptic transmission in the central nervous system, including the spinal dorsal horn.</p> <p>Results</p> <p>To develop a new tool for the identification of <it>in vitro </it>enkephalinergic neurons and to analyze enkephalin promoter activity, we generated transgenic mice for a bacterial artificial chromosome (BAC). Enkephalinergic neurons from these mice expressed enhanced green fluorescent protein (eGFP) under the control of the preproenkephalin (PPE) gene (<it>penk1</it>) promoter. eGFP-positive neurons were distributed throughout the gray matter of the spinal cord, and were primarily observed in laminae I-II and V-VII, in a pattern similar to the distribution pattern of enkephalin-containing neurons. Double immunostaining analysis using anti-enkephalin and anti-eGFP antibodies showed that all eGFP-expressing neurons contained enkephalin. Incubation in the presence of forskolin, an activator of adenylate cyclase, increased the number of eGFP-positive neurons. These results indicate that eGFP expression is controlled by the <it>penk1 </it>promoter, which contains cyclic AMP-responsive elements. Sections obtained from sciatic nerve-ligated mice exhibited increased eGFP-positive neurons on the ipsilateral (nerve-ligated side) compared with the contralateral (non-ligated side). These data indicate that PPE expression is affected by peripheral nerve injury. Additionally, single-neuron RT-PCR analysis showed that several eGFP positive-neurons in laminae I-II expressed glutamate decarboxylase 67 mRNA and that some expressed serotonin type 3 receptors.</p> <p>Conclusions</p> <p>These results suggest that eGFP-positive neurons in laminae I-II coexpress enkephalin and γ-aminobutyric acid (GABA), and are activated by forskolin and in conditions of nerve injury. The <it>penk1</it>-eGFP BAC transgenic mouse contributes to the further characterization of enkephalinergic neurons in the transmission and modulation of nociceptive information.</p

Kinetics of progenitor hemopoetic stem cells in sepsis: Correlation with patients survival?

BACKGROUND: Current theories underline the crucial role of pro-inflammatory mediators produced by monocytes for the pathogenesis of sepsis. Since monocytes derive from progenitor hemopoetic cells, the kinetics of stem cells was studied in peripheral blood of patients with sepsis. METHODS: Blood was sampled from 44 patients with septic syndrome due to ventilator-associated pneumonia on days 1, 3, 5 and 7 upon initiation of symptoms. Concentrations of tumour necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8 and G-CSF were estimated by ELISA. CD34/CD45 cells were determined after incubation with anti-CD45 FITC and anti-CD34 PE monocloncal antibodies and flow cytometric analysis. Samples from eight healthy volunteers served as controls. RESULTS: Median of CD34/CD45 absolute count of controls was 1.0/μl. Respective values of the total study population were 123.4, 112.4, 121.5 and 120.9/μl on days 1, 3, 5 and 7 (p < 0.0001 compared to controls). Positive correlations were found between the absolute CD34/CD45 count and the absolute monocyte count on days 1, 5 and 7. Survival was prolonged among patients with less than 310/μl CD34/CD45 cells on day 1 compared to those with more than 310/μl of CD34/CD45 cells (p: 0.022). Hazard ratio for death due to sepsis was 5.47 (p: 0.039) for CD34/CD45 cells more than 310/μl. Median IL-6 on day 1 was 56.78 and 233.85 pg/ml respectively for patients with less than 310/μl and more than 310/μl CD34/CD45 cells (p: 0.021). CONCLUSION: Stem cells are increased in peripheral blood over all days of follow-up compared to healthy volunteers. Patients with counts on day 1 less than 310/μl are accompanied by increased survival compared to patients with more than 310/μl