Immunogenicity and Safety of Standard and Third-Dose SARS-CoV-2 Vaccination in Patients Receiving Immunosuppressive Therapy.

OBJECTIVE: Immunogenicity and safety following receipt of the standard SARS-CoV-2 vaccination regimen in patients with immune-mediated inflammatory diseases (IMIDs) are poorly characterized, and data after receipt of the third vaccine dose are lacking. The aim of the study was to evaluate serologic responses and adverse events following the standard 2-dose regimen and a third dose of SARS-CoV-2 vaccine in IMID patients receiving immunosuppressive therapy. METHODS: Adult patients receiving immunosuppressive therapy for rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, Crohn's disease, or ulcerative colitis, as well as healthy adult controls, who received the standard 2-dose SARS-CoV-2 vaccination regimen were included in this prospective observational study. Analyses of antibodies to the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were performed prior to and 2-4 weeks after vaccination. Patients with a weak serologic response, defined as an IgG antibody titer of ≤100 arbitrary units per milliliter (AU/ml) against the receptor-binding domain of the full-length SARS-Cov-2 spike protein, were allotted a third vaccine dose. RESULTS: A total of 1,505 patients (91%) and 1,096 healthy controls (98%) had a serologic response to the standard regimen (P < 0.001). Anti-RBD antibody levels were lower in patients (median 619 AU/ml interquartile range [IQR] 192-4,191) than in controls (median 3,355 AU/ml [IQR 896-7,849]) (P < 0.001). The proportion of responders was lowest among patients receiving tumor necrosis factor inhibitor combination therapy, JAK inhibitors, or abatacept. Younger age and receipt of messenger RNA-1273 vaccine were predictors of serologic response. Of 153 patients who had a weak response to the standard regimen and received a third dose, 129 (84%) became responders. The vaccine safety profile among patients and controls was comparable. CONCLUSION: IMID patients had an attenuated response to the standard vaccination regimen as compared to healthy controls. A third vaccine dose was safe and resulted in serologic response in most patients. These data facilitate identification of patient groups at risk of an attenuated vaccine response, and they support administering a third vaccine dose to IMID patients with a weak serologic response to the standard regimen.

Incidence of malignancy in multiple sclerosis: A cohort study in the Danish Multiple Sclerosis Registry.

BACKGROUND: The association between multiple sclerosis and malignancy is controversial and a current appraisal is needed. OBJECTIVE: To determine the incidence of malignancy in patients with multiple sclerosis compared with the general population and in relation to disease-modifying therapy. METHODS: Patients with multiple sclerosis (1995 - 2015) were matched by birth year and sex to individuals without multiple sclerosis in the general population. Patients with multiple sclerosis initiating disease-modifying therapy were evaluated using landmark period analysis. Malignancy risk was assessed by incidence rates, incidence rate ratios, and standardised incidence ratios. RESULTS: The standardised incidence ratio of any malignancy (excluding non-melanoma skin cancer) in patients with multiple sclerosis (n = 10,557) was 0.96 (95% CI 0.88 - 1.06), and there was no increased incidence of specific malignancy types compared with the general population cohort (n = 103,761). At the 48-month landmark period, the age-adjusted incidence per 100,000 person-years of any malignancy (excluding non-melanoma skin cancer) was 436.7 (95% CI 361.0 - 512.4) in patients newly treated with immunomodulator-only and 675.1 (95% CI 130.4 - 1219.9) in patients newly treated with immunosuppressant-only. CONCLUSIONS: There was no increased incidence of malignancy overall or by type in patients with multiple sclerosis compared neither with the general population nor in relation to disease-modifying therapy.

Cognitive remediation plus standard treatment versus standard treatment alone for individuals at ultra-high risk of developing psychosis: Results of the FOCUS randomised clinical trial.

BACKGROUND: Individuals at ultra-high risk (UHR) for psychosis have significant cognitive deficits that can impede functional recovery. Applying cognitive remediation (CR) before the onset of frank psychosis may improve the cognitive and functional prognosis of UHR individuals, however, little is known about the feasibility and efficacy of CR for this population. METHODS: In this randomised, clinical trial 146 individuals at UHR for psychosis aged 18-40 years were randomly assigned to treatment as usual (TAU) or TAU plus cognitive remediation. The CR targeted neurocognitive and social cognitive remediation. Assessments were carried out at 6- and 12-months post baseline. RESULTS: A total of 73 UHR individuals were assigned to TAU and 73 assigned to TAU + cognitive remediation. Compared to the control group, cognitive remediation did not result in significant improvement on the primary outcome; the Brief Assessment of Cognition in Schizophrenia composite score at 6-month follow-up (b = -0.125, 95%CI: -0.23 to 0.172, p = 0.41). Nor did the intervention improve secondary outcomes in clinical symptoms or functioning. Exploratory analyses found emotion recognition latencies to be significantly more reduced in the intervention group at 6-months. At 12-months, the intervention group exhibited significantly better performance on two measures of executive function and visual memory. CONCLUSION: The 20-session treatment protocol was not well received in the UHR group, and unsurprisingly global measures did not improve. The benefit found in isolated neuro- and social cognitive measures after even a few sessions points to a potential for cognitive malleability if people can be engaged sufficiently to practice the skills. Trial registration ClinicalTrial.gov identifier: NCT02098408.

Supplement with whey protein hydrolysate in contrast to carbohydrate supports mitochondrial adaptations in trained runners.

BACKGROUND: Protein supplementation has been suggested to augment endurance training adaptations by increasing mixed muscle and myofibrillar protein synthesis and lean body mass. However, a potential beneficial effect on mitochondrial adaptations is yet to be clarified. The aim of the present study was to investigate the effect of consuming whey protein hydrolysate before and whey protein hydrolysate plus carbohydrate (PRO-CHO) after each exercise session during a six-week training period compared to similarly timed intake of isocaloric CHO supplements on biomarkers of mitochondrial biogenesis, VO2max and performance in trained runners. METHODS: Twenty-four trained runners (VO2max 60.7 ± 3.7 ml O2 kg- 1 min1) completed a six-week block randomized controlled intervention period, consisting of progressive running training. Subjects were randomly assigned to either PRO-CHO or CHO and matched in pairs for gender, age, VO2max, training and performance status. The PRO-CHO group ingested a protein beverage (0.3 g kg- 1) before and protein-carbohydrate beverage (0.3 g protein kg- 1 and 1 g carbohydrate kg- 1) after each exercise session. The CHO group ingested an energy matched carbohydrate beverage. Resting muscle biopsies obtained pre and post intervention were analyzed for mitochondrial specific enzyme activity and mitochondrial protein content. Subjects completed a 6 K time trial (6 K TT) and a VO2max test pre, midway (only 6 K TT) and post intervention. RESULTS: Following six weeks of endurance training Cytochrome C (Cyt C) protein content was significantly higher in the PRO-CHO group compared to the CHO group (p < 0.05), with several other mitochondrial proteins (Succinate dehydrogenase (SDHA), Cytochrome C oxidase (COX-IV), Voltage-dependent anion channel (VDAC), Heat shock protein 60 (HSP60), and Prohibitin (PHB1)) following a similar, but non-significant pattern (p = 0.07-0.14). ß-hydroxyacyl-CoA dehydrogenase (HAD) activity was significantly lower after training in the CHO group (p < 0.01), but not in the PRO-CHO group (p = 0.24). VO2max and 6 K TT was significantly improved after training with no significant difference between groups. CONCLUSION: Intake of whey PRO hydrolysate before and whey PRO hydrolysate plus CHO after each exercise session during a six-week endurance training period may augment training effects on specific mitochondrial proteins compared to intake of iso-caloric CHO but does not alter VO2max or 6 K TT performance. TRIAL REGISTRATION: clinicaltrials.gov , NCT03561337 . Registered 6 June 2018 - Retrospectively registered.

A autobiografia de Wilfred Bion: psicanálise, uma atividade autobiográfica / Wilfred Bion's autobiography: psychoanalysis, an autobiographical activity / La autobiografía de Wilfred Bion: psicoanálisis, una actividad autobiográfica / Autobiographie de Wilfred Bion: psychanalyse, une activité autobiographique

A autora expõe algumas reflexões sobre a autobiografia de Wilfred Bion, especialmente do livro The long weekend. Faz uma analogia com a atividade do analista, considerando a psicanálise uma experiência autobiográfica para a dupla, uma descoberta na relação entre o analista e o analisando.

The author exposes some reflections on the Autobiography of Wilfred Bion especially of the book The long weekend. The author also makes an analogy with the analyst's activity while psychoanalysis is an autobiographical experience for the pair, a finding in the relationship between analyst and analysand.

La autora expone algunas reflexiones acerca de la autobiografía de Wilfred Bion especialmente del libro The long weekend. Hace una analogía con la actividad del analista mientras que el psicoanálisis es una experiencia autobiográfica para la pareja, un descubrimiento en la relación entre el analista y el analizando.

L'auteur expose quelques réflexions sur l'autobiographie de Wilfred Bion, en particulier du livre The long weekend. Il fait une analogie avec l'activité de l'analyste alors que la psychanalyse est une expérience autobiographique pour le couple, une découverte dans la relation entre analyste et analysant.

Shared Decision-Making-Balancing Between Power and Responsibility as Mental Health-Care Professionals in a Therapeutic Milieu.

BACKGROUND: Shared decision-making (SDM) is supposed to position patient and expert knowledge more equal, in which will have an impact on how mental health-care professionals relate to their patients. As SDM has not yet been widely adopted in therapeutic milieus, a deeper understanding of its use and more knowledge of interventions to foster its implementation in clinical practice are required. AIM: To explore how mental health-care professionals describe SDM in a therapeutic milieu as expressed through clinical supervision. The research question was "What are prerequisites for mental health-care professionals to practice SDM in a therapeutic milieu?" METHODS: A qualitative content analysis of data from focus groups dialogues in 10 clinical supervision sessions where eight mental health-care professionals participated was performed. FINDINGS: The theme, practicing SDM when balancing between power and responsibility to form safe care, was based on three categories: internalizing the mental health-care professionals' attributes, facilitating patient participation, and creating a culture of trust. CONCLUSION: SDM is a complex and arduous process requiring appropriate interventions. Clinical supervision is necessary for reflection on SDM and for improving practice in a therapeutic milieu.

Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer.

Background: Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but lack of chronological references makes dating the exact onset of tumours very challenging. Patients and methods: Here, we describe the case of a colorectal cancer (CRC) patient presenting with synchronous lung metastasis and metachronous thyroid, chest wall and urinary tract metastases over the course of 5 years. The chest wall metastasis was caused by needle tract seeding, implying a known time of onset. Using whole genome sequencing data from primary and metastatic sites we inferred the complete chronology of the cancer by exploiting the time of needle tract seeding as an in vivo 'stopwatch'. This approach allowed us to follow the progression of the disease back in time, dating each ancestral node of the phylogenetic tree in the past history of the tumour. We used a Bayesian phylogenomic approach, which accounts for possible dynamic changes in mutational rate, to reconstruct the phylogenetic tree and effectively 'carbon date' the malignant progression. Results: The primary colon cancer emerged between 5 and 8 years before the clinical diagnosis. The primary tumour metastasized to the lung and the thyroid within a year from its onset. The thyroid lesion presented as a tumour-to-tumour deposit within a benign Hurthle adenoma. Despite rapid metastatic progression from the primary tumour, the patient showed an indolent disease course. Primary cancer and metastases were microsatellite stable and displayed low chromosomal instability. Neo-antigen analysis suggested minimal immunogenicity. Conclusion: Our data provide the first in vivo experimental evidence documenting the timing of metastatic progression in CRC and suggest that genomic instability might be more important than the metastatic potential of the primary cancer in dictating CRC fate.

Does High Tobacco Consumption Cause Psychological Distress? A Mendelian Randomization Study.

BACKGROUND: Increasing evidence suggests that smoking influences mental health negatively. This study investigated whether high tobacco consumption is causally related to psychological distress in a Mendelian randomization design, using a variant in the nicotine acetylcholine receptor gene CHRNA3-known to influence individual tobacco consumption-as instrumental variable for tobacco consumption. METHODS: Data from 90 108 participants in the Copenhagen General Population Study was used. Exposures included self-reported cigarettes/day and pack years and the CHRNA3 rs1051730 genotype as instrumental variable for tobacco consumption. Three dimensions of psychological distress were studied: Stress, fatigue, and hopelessness. Analyses with the CHRNA3 genotype were stratified by smoking status. RESULTS: Self-reported amount of smoking was associated with all three dimensions of psychological distress. For instance among participants smoking 30 cigarettes/day or more, the odds ratio (OR) for stress was 1.67 (95% confidence interval [CI] 1.47-1.89) compared to never-smokers. Corresponding ORs for fatigue and hopelessness were 2.18 (95% CI 1.92-2.47) and 3.08 (95% CI 2.62-3.62). Among current smokers, homozygotes and heterozygotes for the CHRNA3 genotype had higher tobacco consumption than noncarriers. Nevertheless, the CHRNA3 genotype was not associated with psychological distress neither in current nor in former or never-smokers. For instance among current smokers, the OR for stress was 1.02 (95% CI 0.91-1.15) among homozygotes compared to noncarriers of the CHRNA3 genotype. CONCLUSIONS: Though a strong association between tobacco consumption and psychological distress was found, there was no clear evidence that high tobacco consumption was causally related to psychological distress. IMPLICATIONS: Smoking is associated with several mental health outcomes and smoking cessation is associated with improved mental health. Causality in the association between smoking and mental health is difficult to establish using observational data. Using a genotype known to influence tobacco consumption as instrumental variable for amount of smoking, we found no clear evidence of a direct causal path between high tobacco consumption and psychological distress. Whatever causes the strong association between tobacco consumption and psychological distress, the co-occurrence is important to consider both in interventions for smoking prevention and cessation.

Disordered eating in French high-level athletes: association with type of sport, doping behavior, and psychological features.

PURPOSE: Over the last few years, disordered eating in athletes has received increasing attention. According to several studies, athletes could be more vulnerable to disordered eating and some characteristics specific to the athletic community could be in favour of an increased risk of poor body image and disturbed eating habits in athletes. However, the literature is sparse and some methodological issues in studies have been pointed out. In this context, we aimed at determining the prevalence of disordered eating in French high-level athletes using clinical interviews of three different clinicians and identifying what are the factors associated with disordered eating in athletes. METHODS: In France, all athletes registered on the French high-level list have to undergo a yearly evaluation. Data collected during the somatic assessment, the dietary consultation, and the psychological of the yearly evaluation were used. Multivariate analysis was performed for identification of factors associated with disordered eating. RESULTS: Out of the 340 athletes included, 32.9% have been detected with a disordered eating. They were difficult to detect by clinicians, as usual criteria did not seem to be reliable for athletes. Competing in sports emphasizing leanness or low body weight was associated with disordered eating; however, gender was not. CONCLUSION: These results highlight the need for the development of specific screening tools for high-level athletes. Furthermore, the identification of factors associated with disordered eating could improve early detection and prevention program effectiveness.

A de novo frameshift in HNRNPK causing a Kabuki-like syndrome with nodular heterotopia.

Kabuki syndrome is a heterogeneous condition characterized by distinctive facial features, intellectual disability, growth retardation, skeletal abnormalities and a range of organ malformations. Although at least two major causative genes have been identified, these do not explain all cases. Here we describe a patient with a complex Kabuki-like syndrome that included nodular heterotopia, in whom testing for several single-gene disorders had proved negative. Exome sequencing uncovered a de novo c.931_932insTT variant in HNRNPK (heterogeneous nuclear ribonucleoprotein K). Although this variant was identified in March 2012, its clinical relevance could only be confirmed following the August 2015 publication of two cases with HNRNPK mutations and an overlapping phenotype that included intellectual disability, distinctive facial dysmorphism and skeletal/connective tissue abnormalities. Whilst we had attempted (unsuccessfully) to identify additional cases through existing collaborators, the two published cases were 'matched' using GeneMatcher, a web-based tool for connecting researchers and clinicians working on identical genes. Our report therefore exemplifies the importance of such online tools in clinical genetics research and the benefits of periodically reviewing cases with variants of unproven significance. Our study also suggests that loss of function variants in HNRNPK should be considered as a molecular basis for patients with Kabuki-like syndrome.

The effectiveness of telephone counselling and internet- and text-message-based support for smoking cessation: results from a randomized controlled trial.

AIM: To compare the effectiveness of proactive telephone counselling, reactive telephone counselling and an internet- and text-message-based intervention with a self-help booklet for smoking cessation. DESIGN: A randomized controlled trial with equal allocation to four conditions: (1) proactive telephone counselling (n = 452), (2) reactive telephone counselling (n = 453), (3) internet- and text-message-based intervention (n = 453) and (4) self-help booklet (control) (n = 452). SETTING: Denmark. PARTICIPANTS: Smokers who had participated previously in two national health surveys were invited. Eligibility criteria were daily cigarette smoking, age ≥ 16 years, having a mobile phone and e-mail address. MEASUREMENTS: Primary outcome was prolonged abstinence to 12 months from the end of the intervention period. FINDINGS: At 12-month follow-up, higher prolonged abstinence was found in the proactive telephone counselling group compared with the booklet group [7.3 versus 3.6%, odds ratio (OR) = 2.2, 95% confidence interval (CI) = 1.2-4.0]. There was no clear evidence of a difference in prolonged abstinence between the reactive telephone counselling group or the internet-based smoking cessation program and the booklet group: 1.8 versus 3.6%, OR = 0.8, 95% CI = 0.6-1.2 and 5.3 versus 3.6%, OR = 1.6, 95% CI = 0.8-3.0, respectively. In the proactive telephone counselling group, the cost per additional 12-month quitter compared with the booklet group was £644. CONCLUSIONS: Proactive telephone counselling was more effective than a self-help booklet in achieving prolonged abstinence for 12 months. No clear evidence of an effect of reactive telephone counselling or the internet- and text-message-based intervention was found compared with the self-help booklet.

A autobiografia de Wilfred Bion: o segredo como fonte de si mesmo / The autobiography of Wilfred Bion: the secret as a source of the self

A autora apresenta trechos da primeira parte da Autobiografia de Wilfred Bion, fazendo conexões com outros autores, com o propósito de ilustrar a necessidade de conhecer e, também, de permanecermos numa área de desconhecimento, o segredo. A busca é pela expressividade e não por justificar-se a priori por meio do entendimento da obra. O psicanalista, assim como o poeta, arrisca, e tenta não resolver o conflito. Entretanto, a mente humana oscila sempre, sendo necessária no processo epistemológico de cada um para conhecer/desconhecer.

The author presents excerpts from the first part Wilfred Bion's Autobiography making connections with other authors in order to illustrate the need to know and also to remain in unawareness realm, the secret. The search is for expressiveness and not by justify oneself a priori through the search of understanding.

PET imaging of tumor hypoxia using 18F-labeled pimonidazole.

BACKGROUND: Tumor hypoxia contributes to loco-regional failure, and for optimal treatment planning, knowledge about tumor hypoxia in individual patients is required. Nitroimidazole-based tracers, which are retained in hypoxic cells, allow PET-based assessment of tumor hypoxia, but current tracers are characterized by slow tracer retention and clearance, resulting in low inter-tissue contrast. Pimonidazole is an immune detectable hypoxia marker widely used for detection of hypoxia in tumor samples. Pimonidazole has excellent chemical properties for hypoxia imaging, but labeling for non- invasive assay has not been attempted. Here we labeled pimonidazole with (18)F ([(18)F]FPIMO). MATERIAL AND METHODS: [(18)F]FPIMO was produced by fluorination of 1-[2-O-tosyl-3-(2-nitroimidazole-1-yl)-propyl]-piperidine, which resulted in two isomeric interchangeable forms (named "5" and "6") with a radiochemical purity of 91-100%. [(18)F]FPIMO was tested by incubation of two different tumor cell lines at high and low oxygen levels. [(18)F]FPIMO was also administered to tumor-bearing mice and tracer retention in tumors, non-hypoxic reference tissues and tissues involved in drug metabolism/clearance was evaluated by various techniques. RESULTS AND CONCLUSIONS: Retention of [(18)F]FPIMO was strongly hypoxia-driven in vitro, but isomeric form "5" was particularly promising and reached impressive anoxic-to-oxic retention ratios of 36 and 102, in FaDuDD and SiHa cells, respectively, following three hours of tracer incubation. This was equal to or higher than ratios measured using the established hypoxia tracer [(18)F]FAZA. [(18)F]FPIMO also accumulated in tumors grown in mice, and reached tumor levels that were two to six-fold higher than in muscle three hours post-administration. Furthermore, the intra-tumoral distribution of [(18)F]FPIMO (autoradiography) and unlabeled pimonidazole (immunohistochemistry) was largely identical. Nonetheless, [(18)F]FPIMO proved inferior to [(18)F]FAZA, since absolute tumor signal and intra-tumoral contrast was low, thus compromising PET imaging. Low tumor signal was coupled to extensive tracer accumulation in liver and kidneys, and analysis of blood metabolites revealed that [(18)F]FPIMO was metabolized rapidly, with little parent compound remaining 15 minutes post-administration. Ongoing work focuses on the possibility of labeling pimonidazole in different positions with (18)F to improve tracer stability in vivo.

Survival and development of a stored-product pest, Sitophilus zeamais (Coleoptera: Curculionidae), and its natural enemy, the parasitoid Lariophagus distinguendus (Hymenoptera: Pteromalidae), on transgenic Bt maize.

BACKGROUND: The effect of transgenic maize (Zea mays L.) containing a lepidopteran-specific Bt toxin on a stored-product pest, Sitophilus zeamais Motschulsky, and its parasitoid, Lariophagus distinguendus Förster, was examined in the laboratory to test the impact of transgenic maize on stored-product pests and their biological control. RESULTS: Weevils were not harmfully affected by transgenic Bt maize in their development characteristics (development time, body mass), and females emerging from transgenic maize kernels were larger. However, significantly fewer parasitoid females emerged from weevils that developed in transgenic kernels, although parasitoids did not develop more slowly and were not different in size or mass from their conspecifics emerging from hosts in non-transgenic maize kernels. CONCLUSION: The emergence of female parasitoids was reduced in transgenic Bt maize, and this effect cannot be explained by the known lepidopteran-specific toxicity of Bt Cry1Ab toxin.

Tumour hypoxia imaging with 18F-fluoroazomycinarabinofuranoside PET/CT in patients with locally advanced rectal cancer.

OBJECTIVE: The aim of this study was to investigate the feasibility of F-fluoroazomycinarabinofuranoside (F-FAZA) positron emission tomography (PET)/computed tomography (CT) in patients with locally advanced rectal cancer. MATERIALS AND METHODS: The study included 14 patients with locally advanced rectal cancer. Before chemoradiotherapy, PET/CT with F-FAZA was performed with static 15 min images 2 h after injection of F-FAZA. Attenuation correction was obtained with a low-dose CT, and a contrast-enhanced CT was performed immediately after the PET scan. RESULTS: F-FAZA uptake [mean and maximum standardized uptake value (SUVmean) and (SUVmax)] was significantly higher in rectal tumours than in both muscles (P<0.003) and normal intestinal walls (P<5×10). The tumour to muscle (T/M) ratios ranged from 1.19 to 3.05 with a mean of 1.97, whereas the tumour to intestinal wall (T/I) ratios had values of 1.73-5.81 with a mean of 2.83. Intense activity accumulating in the bladder produced obvious scattered activity, which spread into the surrounding tissue. Tumour volumes excluding scatter were therefore determined, in which the SUVmax and SUVmean were also significantly higher than in both muscles (P<0.004) and normal intestinal walls (P<2×10) and had T/M ratios of 1.19-2.72 with a mean of 1.85 and T/I ratios of 1.71-5.40 with a mean of 2.67. The individual SUVmax, SUVmean, T/M and T/I values were significantly higher in the entire tumour volume compared with the tumour volume adjusted for scatter from the urinary bladder (P<0.005), although the absolute differences were small. CONCLUSION: F-FAZA PET/CT is feasible for visualization of hypoxia in patients with rectal cancer, but scattered activity from the urinary bladder should be taken into consideration.

Lethal doses of ozone for control of all stages of internal and external feeders in stored products.

BACKGROUND: Gaseous ozone (O(3)) has potential for control of insects in stored grain. Previous studies have focused on freely exposed insects. Immatures of internal pests (e.g. Sitophilus spp. and most stages of Rhyzopertha dominica F.) are protected within kernels and probably require higher doses and/or longer treatment times for full control. A laboratory study determined the doses of ozone necessary for full control of freely exposed and internal stages of eleven stored-product pest species. Test insects were three species of Sitophilus, R. dominica, Tribolium confusum Jacquelin du Val, T. castaneum Herbst, Plodia interpunctella Hübner, Sitotroga cerealella Olivier, Oryzaephilus surinamensis L., Ephestia kuehniella Zeller and Stegobium paniceum L. Insects were exposed to continuous flows of ozone in doses of 10-135 ppm and exposure times of 5-8 days. Dose-mortality bioassays were conducted on three species of Sitophilus and P. interpunctella. RESULTS: Freely exposed stages (with a few exceptions) were controlled with 35 ppm of ozone for 6 days. Full mortality of internal stages within kernels required exposure to 135 ppm for 8 days. CONCLUSION: This study confirms that higher doses and/or longer treatment times are necessary for control of internal stages of stored-product pests.

Circulating HER2 DNA after trastuzumab treatment predicts survival and response in breast cancer.

BACKGROUND: Only a subset of breast cancer patients responds to the HER2 inhibitor trastuzumab, and methods to identify responders are needed. PATIENTS AND METHODS: We studied 28 patients with metastatic breast cancer that had amplified human epidermal growth factor receptor 2 (HER2) genes in their primary tumour and were treated with a combination of trastuzumab and chemotherapy. Plasma was collected and amplification of the HER2 gene in circulating DNA and the amounts of the extracellular domain (ECD) of HER2 were measured just before first treatment (n=28) and just before second treatment three weeks later (HER2 DNA (n=22), HER2 ECD (n=23)). RESULTS: Pre-treatment levels of HER2 gene amplification and HER2 ECD did not correlate to clinical parameters. However, 9 out of 22 patients had a more than a 14% (2 x SD) reduction in HER2 gene amplification following treatment and showed improved response (p=0.02), and overall survival (p=0.05). HER2 ECD kinetics did not correlate to clinical data. CONCLUSION: We suggest that a decrease in HER2 gene amplification in the plasma predicts a more favourable response to trastuzumab.

A família institucional e a fantasmática do analista / The institutional and phantasmal family of the analyst

O autor propõe a existência de intensa interação entre as duas famílias do analista: a histórica, da infância, e a institucional, de sua formação. Para ele, ambas intervêm no trabalho do analista com seu paciente, no plano da fantasia interior, em grau diferente, segundo os diversos momentos de trabalho. Mostra-se que o elemento comum à experiência infantil e a analítica é a imensa oportunidade de profunda introjeção. No percurso do jovem psicanalista, há momentos introjetivos decisivos, que vão fundar e constituir as bases culturais, teóricas e clínicas do seu “Eu de trabalho” (AU)

The author proposes the existence of intense interaction between the analyst’s two families, the historical one of his infancy, and the institutional one, of his psychoanalytic education. In his opinion, they both step in the analyst’s work with his patient, on the level of his inner fantasy, and in different degrees according to the diverse moments of the work. He points out that the common element between the infantile experience and the analytic one is the enormous opportunity of profound introjection. There are important moments that favor introjection in the young analyst’s course, which establish and constitute the cultural, theoretical and clinical foundations of his Working Self (AU)

Sequence patterns associated with disordered regions in proteins.

The relationship between amino acid sequence and intrinsic disorder in proteins is investigated. Two databases, one of disordered proteins and the other of globular proteins, are analyzed and compared in order to extract simple sequence patterns of a few amino acids or amino acid properties that characterize disordered segments. It is found that a number of reliable, nonrandom associations exists. In particular, two types of patterns appear to be recurrent: a proline-rich pattern and a (positively or negatively) charged pattern. These results indicate that local sequence information can determine disordered regions in proteins. The derived patterns provide some insights into the physical reasons for disordered structures. They should also be helpful in improving currently available prediction methods.