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Depression is a disabling mental condition that reduces the quality of life regardless of age and circumstances. Late-life depression may be especially impairing due to its relationship with poor physical and mental health. Repeated or prolonged exposures to stressful events deserve a particular interest among late-life depression risk factors. One factor that may help to cope with these stressful situations is the resilience. The objective of the study was to examine the moderating effect of resilience on the relationship between perceived stress (PS) and depression. A total of 1020 community-dwelling older adults aged from 60 to 101 years (M = 68.5, SD = 6.99) completed the Perceived Stress Scale, Hospital Anxiety and Depression Scale, and Brief Resilience Scale. A moderation effect has been tested using PROCESS for SPSS. Depressive symptomatology was positively related to PS (r = .598; p < .001) and inversely related to resilience (r = − .444; p < .001). Moreover, the negative impact of PS on depressive symptoms was buffered for individuals with higher resilience (β = − .014; p < .001). The resilience could be an adaptive strategy to cope with stress and reduce depression in community-dwelling older adults.

Aim: The CAVIDIOR study evaluated quality of life (QoL) in patients with breakthrough cancer pain receiving palliative radiation therapy in radiation oncology departments (RODs) in Spain. Patients & methods: Prospective observational study at 11 Spanish RODs (July 2016–November 2017). QoL was assessed using Short Form Health Survey 12. Secondary end points were sleep quality, caregiver burden and patient/perception of improvement. Results: QoL improved according to the Short Form Health Survey 12 mental component. Sleep quality and caregivers’ burden improved significantly. Conclusion: Breakthrough cancer pain is highly prevalent and can be substantially reduced with appropriate diagnosis and management in RODs. Along with the QoL questionnaire, sleep quality and caregiver burden provide a more comprehensive assessment of overall health status in patients receiving radiation therapy in RODs. Clinical trial registration: NCT02836379 ( ClinicalTrials.gov )

Background The long-term trajectory of depressive symptoms has a heterogeneous pattern. Identifying factors associated with different trajectories and outcomes may have important theoretical and clinical implications. This study explored patterns of depressive symptom trajectory from adolescence to adulthood, and their relationship with subsequent psychiatric disorders. Method A sample of 816 participants (58.8% girls; M = 16.58 years old at baseline, SD = 1.21) from a large community sample were interviewed four times during adolescence and adulthood. Depressive symptoms were also assessed. Symptom trajectory identification was based on latent class mixed modeling. Logistic regression was used for predicting emotional and drug use disorder over age 30. Results Three trajectories of depressive symptoms were identified: "decreasing symptom" (decreasing trajectory of symptoms; 15.1% of participants), "increasing symptom" (initially decreasing pattern of symptoms and then increasing; 6.1% of participants), and "normative symptom" (consistently low symptom levels; 78.8% of participants). Predictors of the increasing symptom trajectory were high level of loneliness and state anxiety, presence of an emotional disorder, and low involvement in physical exercise at baseline. This trajectory membership predicted the development of anxiety disorders over age 30. Predictors of the decreasing symptom class were being female and high level of worry at baseline. Conclusions Long-term trajectories of depressive symptoms are heterogeneous, with each trajectory having different predictors and are associated with different outcomes during adulthood.

Highlights • There was a high prevalence of substance use among adolescents living in Indonesia, Laos, Malaysia, Myanmar, Philippines and Thailand. • Heavy drinking was more prevalent among adolescents with higher than lower levels of internalizing problems. • Regular alcohol and amphetamine use was common among adolescents who were frequently bullied by their peers. • Binge drinking was common among adolescents who reported feelings lonely., Substance use is a common public health problem among adolescents in low- and middle-income countries (LMICs), however, factors that are associated with this condition are not clearly understood. The aim of the present study was to examine personal and interpersonal factors that contribute to risk for substance use among adolescents in six ASEAN (Association of Southeast Asian Nations) LMICs (i.e., Indonesia, Laos, Malaysia, Myanmar, Philippines and Thailand). Data of 57,825 adolescents (52.64% girls; median age = 14 years old) who participated in the Global School-based Student Health Survey (GSHS) were analysed. After the weighted prevalence was estimated for each country, multilevel models were employed to examine the influence of the risk factors on the prevalence of substance use across the countries. The results indicated a high prevalence of substance use among adolescents in all these six ASEAN LMICs. Alcohol use, smoking and drug use were more prevalent among adolescents in Thailand, Laos and Philippines. Adolescents who were bullied and who had no close friends had a high prevalence of alcohol and drug use. Problematic drinking and smoking were more prevalent among older adolescents, and smoking and drug use were more prevalent among boys. Furthermore, frequent worry, loneliness and regular physical activity were found to predict adolescents’ heavy and binge drinking. This study contributed to knowledge on risk factors for specific substance use among adolescents and drew attention for the urgent need to strengthen the intervention, law policies and professional support for reducing substance use in ASEAN LMICs.

Background Anxiety disorders frequently have an onset during adolescence, which when left untreated could lead to a chronic course and outcome. This study aimed to examine the way in which a cognitive behaviour therapy-based programme (Super Skills for Life – adolescent version; SSL-A) could change the course of anxiety symptoms through adolescent's behavioural performance and cardiac function. Method Sixty-one adolescents at risk of developing an anxiety disorder (45.30% boys; M = 13.76 years, SD = 0.32) were randomly assigned to either an intervention (IG), placebo (PG), or a waitlist group (WG). Adolescents in the IG participated in SSL-A over an 8-week period. Adolescents in the PG participated in an 8-session school-work programme. Adolescents in the WG did not receive any intervention. Anxiety symptoms were assessed every six months, twice before the intervention, as well as at the post-intervention and six months after the intervention. Participants in the IG additionally underwent a stressful task to assess behavioural performance and cardiac adjustment. Results Adolescents in the IG significantly reported lower levels of social phobia and generalised anxiety symptoms at the follow-up assessment compared to the adolescents in the PG and the WG. They also showed a significant improvement in vocal quality and lower discomfort during a stressful task at post-intervention, and showed attenuated cardiac recovery indexes, in terms of sample entropy. Limitations The study has a small sample size. Conclusion SSL-A changed the natural course of anxiety symptoms, as shown by a significant reduction in social phobia and generalised anxiety symptoms, and a significant improvement in behaviour and physiological (cardiac) function during a stressful situation.

Coronavirus illness 2019 (COVID-19) is an airways infection caused by the new coronavirus (SARS-CoV-2) which has been quickly disseminated all over the world, affecting to the general population including women in pregnancy time. As being a recent infection, the evidence that supports the best practices for the management of the infection during pregnancy is limited, and most of the questions have not been completely solved yet. This publication offers general guidelines focused on decision-making people, managers, and health's teams related to pregnant women attention and newborn babies during COVID-19 pandemic. Its purpose is to promote useful interventions to prevent new infections as well as prompt and adequate attention to avoid serious complications or deaths, trying to be adapted to the different contexts in which attention to expectant mothers is provided. Guidelines are set within a well-scientific evidence and available recommendations up to date.La enfermedad por coronavirus 2019 (COVID-19) es una infección de las vías respiratorias causada por un nuevo virus (SARS-CoV-2) que se ha diseminado rápidamente en el mundo, afectando a la población general, incluida la población de mujeres cursando un embarazo. Por ser una infección de aparición reciente, la información que soporta las mejores prácticas para el manejo de la infección durante la gestación es escasa y muchas de las preguntas no están completamente resueltas.Esta publicación brinda lineamientos generales orientados a tomadores de decisión, gerentes y equipos de salud en relación con el cuidado de mujeres gestantes y recién nacidos durante la pandemia por COVID 19. Su finalidad es promover intervenciones beneficiosas para prevenir nuevos contagios, y la atención oportuna y adecuada de la gestante para evitar complicaciones graves y/o muertes, adecuándose a los distintos contextos en los que se proporciona atención médica. Los lineamientos se enmarcan en la mejor información científica y las recomendaciones disponibles hasta la fecha.

Purpose Major depressive disorder (MDD) and social phobia (SP) are both common and highly co-occurring psychiatric disorders. This study used symptom network analysis approach to examine comorbidity structure and the complex symptom dynamics which may play a role in the co-occurrence of MDD and SP. Method Data comes from the National Comorbidity Survey – Adolescent Supplement, a nationally representative survey of adolescents ages 13 to 18 years. This study examined data of adolescents with a lifetime diagnosis of MDD (n = 597), SP (n = 708), and adolescents with comorbid MDD and SP (n = 189). Networks were estimated by means of 26 symptoms from both disorders. Results All MDD and SP symptoms were involved in the network of both pure disorders (MDD; SP) and comorbid condition (MDD + SP). Network structure was different between the pure disorders (p = 0.014), but not when comparing each of these disorders that have comorbid condition. Depressive symptoms of poor self-esteem and suicidal symptoms were central (i.e., showed a higher influence) in the symptom network for the pure disorders and for the comorbid condition. Other key symptoms in the comorbid condition network were two depressive symptoms: feelings of worthlessness and anhedonia. SP and MDD networks showed two common key SP symptoms: feeling uncomfortable when meeting new people and feeling uncomfortable talking to people do not know well. Conclusion The study of symptom dynamics will provide useful targets for preventing the development of comorbid disorders as well as new lines of intervention to deal with key symptoms of psychiatric disorders.

There is growing evidence that loneliness is associated with mild cognitive impairment (MCI) and dementia. However, the extent of this association remains unclear. A systematic review and meta-analysis of longitudinal studies examining this association was conducted. Six electronic databases were searched from inception to November 15th 2018. A random-effects meta-analysis was performed to obtain pooled estimates and 95% CIs. Studies were also assessed for heterogeneity, methodological quality and publication bias. A total of 4270 hits were retrieved based on the initial search strategy and ten studies met the eligibility criteria involving 37339 individuals (mean age from 64.9 to 83.1 years). Variation between studies was present for the measurement of loneliness as well as for the case ascertainment of MCI and dementia. Loneliness was positively associated with increased risk of dementia (overall RR = 1.26; 95% CI = 1.14, 1.40; n = 8). Due to lack of sufficient data, we could not explore the association between loneliness and risk of MCI through a meta-analysis, but limited evidence suggests a potential effect of loneliness on MCI. A further understanding of the deleterious effects of loneliness on MCI and dementia may assist the design of environmental and psychological interventions to prevent or delay the onset of these neuropsychiatric conditions.

Background Whether worldwide increases in life expectancy are accompanied by a better health status is still a debate. People age differently, and there is a need to disentangle whether healthy-ageing pathways can be shaped by cohort effects. This study aims to analyse trends in health status in two large nationally representative samples of older adults from England and the USA. Methods The sample comprised 55 684 participants from the first seven waves of the English Longitudinal Study of Ageing (ELSA), and the first 11 waves of the Health and Retirement Study (HRS). A common latent health score based on Bayesian multilevel item response theory was used. Two Bayesian mixed-effects multilevel models were used to assess cohort effects on health in ELSA and HRS separately, controlling for the effect of household wealth and educational attainment. Results Similar ageing trends were found in ELSA (β = –0.311; p Conclusions Health inequalities have increased in recent cohorts, with the wealthiest participants presenting a better health status in both the USA and English populations. Actions to promote health in the ageing population should consider the increasing inequality scenario, not only by applying highly effective interventions, but also by making them accessible to all members of society.

Background To date, available data on premature aging in young HIV-infected adults are scarce and no reports offer comprehensive assessment of telomere shortening (TS) in relation to subclinical atherosclerosis (SCA). In this study, we investigate if telomere shortening and immune activation markers are associated with SCA, which is one of the main degenerative diseases in young HIV-infected adults. Methods A descriptive cross-sectional study was carried out in 149 HIV-infected patients on stable antiretroviral regimen (ART). Carotid intima-media thickness (cIMT) was estimated by carotid ultrasound. Quantitative singleplex PCR was performed to evaluate TS. The expression of activation/senescence markers was evaluated by multiparametric flow cytometry. Results TS was observed in 73 patients (49%). Higher cIMT was observed in patients with TS than those without it (0.86 vs. 0.80 mm; p=0.041). Patients under the age of 50 (defined as young adults) with TS showed higher absolute numbers of activated lymphocyte T cells CD8+CD38+ (3.94 vs. 2.34 cell/μl; p=0.07) and lymphocyte B cells CD19+CD38+ (3.07 vs. 2.10 cell/μl; p=0.004) compared to those without TS. In the multivariate analysis, the only factor independently associated with TS was the absolute number of lymphocyte T cells CD8+CD38+ T cells (OR = 1.18; 95%-CI = 1.00-1.39; p = 0.05). Conclusion Young HIV-infected adults show premature biological aging with accentuated immune activation. Chronic inflammation with excessive T-cells activation could be associated to TS, premature aging, and SCA in young HIV-infected adults.

The COVID-19 ongoing pandemic constitutes a major challenge for countries throughout the world due to the rapid spread of SARS-CoV-2 and devastating consequences in health. No one is free from COVID-19 impact. In this regard, pregnant women are not the exception. The COVID-19 outbreak represents a massive source of stressful agents for women and their babies during the perinatal period. The COVID-19 pandemic has been suggested to potentially have short- and long-term detrimental effects on pregnant women and the baby. These adverse consequences range from mental to medical diseases. During the last centuries, several dreadful and fatal incidents have put pregnant women and their babies at higher risk of mortality and health deterioration. For example, it has been informed that women exposed to the 1918 flu pandemic (commonly known as the Spanish flu) while pregnant showed higher rates of premature delivery in the short term. Long-term consequences have also been reported and individuals (both males and females) who were exposed to the 1918 flu pandemic while in utero had a higher risk of developing schizophrenia, diabetes, coronary heart disease or cancer throughout their lifespan.

Background Suicide is the second leading cause of death for young people. Objective: To assess mental disorders as risk factors for suicidal behaviour among adolescents and young adults including population-based longitudinal studies. Method We conducted a systematic literature review. Bibliographic searches undertaken in five international databases and grey literature sources until January 2017 yielded a total of 26,883 potential papers. 1701 full-text articles were assessed for eligibility of which 1677 were excluded because they did not meet our eligibility criteria. Separate meta-analyses were conducted for each outcome (suicide death and suicide attempts). Odds ratio (OR) and 95% confidence intervals (95%CI) and beta coefficients and standard errors were calculated. Results 24 studies were finally included involving 25,354 participants (12–26 years). The presence of any mental disorder was associated with higher risk of suicide death (OR = 10.83, 95%CI = 4.69–25.00) and suicide attempt (OR = 3.56; 95%CI 2.24–5.67). When considering suicidal attempt as the outcome, only affective disorders (OR = 1.54; 95%CI = 1.21–1.96) were significant. Finally, the results revealed that psychiatric comorbidity was a primary risk factor for suicide attempts. Limitations Data were obtained from studies with heterogeneous diagnostic assessments of mental disorders. Nine case-control studies were included and some data were collected in students, not in general population. Conclusions Mental disorders and comorbidity are strong predictors of suicide behaviour in young people. Detection and management of the affective disorders as well as their psychiatric comorbidity could be a crucial strategy to prevent suicidality in this age group.

Introduction Suicide is one of the leading causes of avoidable death. Gathering national data on suicidal behaviour incidence is crucial to develop evidence-based public policies. The study has two primary objectives: (1) to determine the incidence of suicide attempts in Spain and related risk factors, and (2) to analyze the efficacy of secondary prevention programmes to prevent suicide re-attempting in comparison to treatment as usual (TAU). Materials and methods Multisite, coordinated, cohort study with three nested randomized controlled trials. A cohort of 2000 individuals (age >=12) with suicidal behaviour will be recruited at ten sites distributed across Spain. Assessments will be conducted within 10 days of the suicide attempt (V0-baseline visit) and after 12 months (V4-last visit) and will include clinician reported and participant reported outcomes (PROs). Between V0 and V4, PROs will be collected remotely every three months (V1, V2 and V3). Optatively, cohort participants will participate in three nested randomized-controlled-trials (RCTs) evaluating different secondary prevention interventions: Participants aged 18 years and older will be randomly allocated to: Telephone-based Management + TAU vs. TAU or iFightDepression-Survive + TAU vs. TAU. Participants aged between 12 and 18 years will be allocated to a specific intervention for youths: Self Awareness of Mental Health + TAU vs. TAU. Results This study will provide interesting data to estimate suicide attempt incidence in Spain. and will provide evidence on three. Conclusions Evidence on three potentially efficacious interventions for individuals at high risk of suicide will be obtained, and this could improve the treatment given to these individuals. Trial registration NCT04343703

Mujer de 67 años pluripatológica, diagnosticada de insuficiencia cardíaca, fibrilación auricular y portadora de prótesis mitral que acudió a Consultas Externas por cuadro de disnea, anemia y síndrome constitucional que, tras empeoramiento clínico, requirió ingreso en planta de Medicina Interna para completar estudio y tratamiento. Se realizó un estudio amplio, con diagnóstico diferencial de las múltiples causas de síndrome constitucional, sin grandes resultados hasta la realización de la ecocardiografía transesofágica, en la que se evidenció un hallazgo específico que, tras el tratamiento adecuado, permitió la resolución del cuadro clínico así como una gran mejoría clínica en la paciente.

Highlights • The prevalence of regular alcohol use was the highest among adolescents in Zambia but the lowest in Senegal. • The prevalence of problematic alcohol use was higher in Argentina and Colombia than in any other low- and middle-income countries. • The prevalence of regular and problematic alcohol use was the lowest in countries with Muslim and Buddhist religions. • Samoa had the highest prevalence of smoking as well as in marijuana and amphetamine consumption., Introduction Adolescence is a critical developmental stage for the initiation of substance use worldwide. However, the prevalence of various types of substances consumed by adolescents living in low- and middle- income countries (LMICs) across different continents is not fully understood. The aims of the present study were to estimate the prevalence of regular and problematic substance use among adolescents in 73 LMICs across different continents and to explore the role of country-specific factors on this prevalence. Method Data of 314,187 adolescents (52.79% girls; median age = 15 years old) who participated in the Global School-based Student Health Survey (GSHS) were analysed. After estimating the weighted prevalence for each country, multilevel models were used to examine the influence of country-specific factors on the prevalence of substance use across 73 LMICs. Results The results indicated that problematic alcohol use was more prevalent in LMICs with higher income levels. The prevalence of regular alcohol use was the highest in Zambia. Regular and problematic alcohol use was the least prevalent in Senegal and Myanmar. The findings also revealed that smoking and the consumption of marijuana and amphetamine were the most common among adolescents in Samoa, whereas the prevalences for these substances were the lowest in Laos. Conclusion Economic wealth, religion and geographical factors seem to have a role in determining the prevalence of substance use among adolescents in LMICs.

Background: The rapid growth of the size of the older population is having a substantial effect on health and social care services in many societies across the world. Maintaining health and functioning in older age is a key public health issue but few studies have examined factors associated with inequalities in trajectories of health and functioning across countries. The aim of this study was to investigate trajectories of healthy ageing in older men and women (aged ≥45 years) and the effect of education and wealth on these trajectories. Methods: This population-based study is based on eight longitudinal cohorts from Australia, the USA, Japan, South Korea, Mexico, and Europe harmonised by the EU Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. We selected these studies from the repository of 17 ageing studies in the ATHLOS consortium because they reported at least three waves of collected data. We used multilevel modelling to investigate the effect of education and wealth on trajectories of healthy ageing scores, which incorporated 41 items of physical and cognitive functioning with a range between 0 (poor) and 100 (good), after adjustment for age, sex, and cohort study. Findings: We used data from 141 214 participants, with a mean age of 62·9 years (SD 10·1) and an age range of 45–106 years, of whom 76 484 (54·2%) were women. The earliest year of baseline data was 1992 and the most recent last follow-up year was 2015. Education and wealth affected baseline scores of healthy ageing but had little effect on the rate of decrease in healthy ageing score thereafter. Compared with those with primary education or less, participants with tertiary education had higher baseline scores (adjusted difference in score of 10·54 points, 95% CI 10·31–10·77). The adjusted difference in healthy ageing score between lowest and highest quintiles of wealth was 8·98 points (95% CI 8·74–9·22). Among the eight cohorts, the strongest inequality gradient for both education and wealth was found in the Health Retirement Study from the USA. Interpretation: The apparent difference in baseline healthy ageing scores between those with high versus low education levels and wealth suggests that cumulative disadvantage due to low education and wealth might have largely deteriorated health conditions in early life stages, leading to persistent differences throughout older age, but no further increase in ageing disparity after age 70 years. Future research should adopt a lifecourse approach to investigate mechanisms of health inequalities across education and wealth in different societies. Funding: European Union Horizon 2020 Research and Innovation Programme., The ATHLOS project was funded by the European Union Horizon 2020 Research and Innovation Programme (grant number 635316). This study was supported by the 5-year ATHLOS project

Objective The goal of this systematic-review and meta-analysis was to assess whether high maternal stress during pregnancy is associated with the development of pediatric pathology. Design Epidemiological peer-reviewed studies published in English or Spanish assessing associations between maternal stress during pregnancy and psychiatric and medical diseases were selected. Participants We retrieved 73,024 citations; 42 studies meeting inclusion criteria were assessed. Overall sample included 65,814,076 women. Findings Overall odds ratio for the development of a medical disease was OR=1.24 (CI95=1.11, 1.39), Z=3.85, p Key conclusions We concluded that exposure to high levels of stress during pregnancy are associated with autism spectrum disorder, obesity, and infantile colic in offspring. Implications for practice Maternal stress during pregnancy should be addressed to tackle its potential impact in health across the life span.

This study aimed to examine how loneliness contributes to metabolic dysregulation among older adults with depression and determine the relative contribution of loneliness to the development of chronic diseases in late adulthood. Harmonised data from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project were used. Concretely, the sample comprised 6195 participants (53.95% women; M = 61.30 years, SD = 7.11) from three European cohorts. Three groups were considered: control group (CG); depressive symptom episode group (DEP); and a group with depression and loneliness (DEP + LONE). A metabolic score was estimated using anthropometric and blood indicators, by means of multi-indicator multi-causes (MIMIC) modelling and after controlling for sociodemographic and health-related covariates. Group-comparison was based on measurement-invariance procedures. Multimorbidity development was predicted at follow-up considering the study group and relevant covariates. All the analyses were sex-specific. As a result, measurement invariance revealed the influence of group (ΔCFI = −0.017 for male participants and ΔCFI = −0.009 for female ones) on metabolic scores in both sexes. Metabolic scores were significantly lower (i.e., they had more metabolic risk) in DEP + LONE women in comparison to women from the other groups. DEP men showed the lowest metabolic scores but those from the DEP + LONE group showed meaningfully lower scores than CG men (d = 1.35). In terms of multimorbidity prediction, DEP + LONE group membership significantly predicted the outcome in both sexes; DEP group membership significantly predicted multimorbidity at follow-up in women. In summary, these results highlight the relevant contribution of loneliness in depression-related metabolic dysregulation in the short- (concurrent metabolic risk) and long-term (chronic condition development). Moreover, sex-specific mechanisms seem to be involved in metabolic alterations of depressed people showing loneliness feelings. This study calls for action to reduce the impact of loneliness in old age and to promote healthy ageing.

Depression in old age deserves special attention in view of the fact of progressive population ageing, because of the way in which depression and risk factors interact in this period of life and the particularly negative impact of late-life depression on health and quality of life. This editorial aims to provide some insight into longitudinal aspects of depression in old age. Depression may follow varying trajectories (e.g. episode emergence, recurrence) across the lifespan. Late-life depression is not an exception. A symptom-based approach is presented as an appropriate research method to study the predictors and course of affective syndromes in old age. Findings from our studies on depressive symptom trajectories in old age revealed that participants with a course of unremitting elevated symptoms showed the highest levels of loneliness across the trajectory groups and that participants with subclinical symptoms also showed higher levels of loneliness than their counterparts with a minimal-symptom course trajectory. This highlights the need to address loneliness as a way of dealing with depression in old age., This work was supported by the 5-year Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project. The ATHLOS project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 635316; Instituto de Salud Carlos III-FIS under grant number PI16/00218; and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM).

Tomato is a crop with the greatest economic importance in the world and salinity stress causes a reduction in the quantity and quality of crop production. Today the main challenge in world agriculture is to sustain the continuously growing global population, and this becomes more difficult due to climatic change, as this imposes further abiotic stress. The aim of this study was to determine the involvement of the TCA cycle in resistance to salinity in two genotypes of tomato. We found that the cv. Grand Brix enhances the tricarboxylic acid (TCA) cycle activity as a mechanism of resistance to salt stress, while the cv. Marmande RAF does not have this mechanism. This causes a greater accumulation of organic acids in Grand Brix which favours even more resistance to salt stress. We propose an idea of how the oxaloacetate could help to control Na + excess in the cv. Grand Brix.

Introduction: Disorders of lipid metabolism caused by genetic mutations, acquired risk factors and risk conditions, or both, are common in children. While some manifest clinical signs and symptoms, children with genetic mutations such as familial hypercholesterolemia are asymptomatic and generally of normal weight. Nonetheless, life-long elevation of cholesterol plays a key role in the initiation and progression of atherosclerosis, starting in childhood, and increases risk of premature cardiovascular disease-related events, such as myocardial infarction and stroke.Areas covered: Genetic mutations and acquired risk factors and conditions that cause dyslipidemia are outlined. Current guidelines for screening, interpretation of test results, implementation of therapy and monitoring are reviewed, and the role of genetic testing is discussed.Expert opinion: In addition to a heart healthy lifestyle, those with inherited disorders of lipid metabolism often benefit from timely medical intervention to redu...

The authors would like to thank all those clinicians that are taking care of the entire global population during this pandemic. Special thanks to obstetricians and midwives who have been looking after pregnant women and forthcoming generations., Background: There is inconclusive evidence regarding congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. A narrative review was conducted with the aim of guiding clinicians on the management of pregnant women with respect to congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections and breastfeeding during the COVID-19 pandemic. Methods: Searches were conducted in Web of Science, PubMed, Scopus, Dialnet, CUIDEN, Scielo, and Virtual Health Library to identify observational, case series, case reports, and randomized controlled trial studies assessing the transmission of SARS-CoV-2 from mother to baby and/or through breastfeeding during the COVID-19 pandemic. Results: A total of 49 studies was included in this review, comprising 329 pregnant women and 331 neonates (two pregnant women delivered twins). The studies were performed in China (n = 26), USA (n = 7), Italy (n = 3), Iran (n = 2), Switzerland (n = 1), Spain (n = 1), Turkey (n = 1), Australia (n = 1), India (n = 1), Germany (n = 1), France (n = 1), Canada (n = 1), Honduras (n = 1), Brazil (n = 1), and Peru (n = 1). Samples from amniotic fluid, umbilical cord blood, placenta, cervical secretion, and breastmilk were collected and analyzed. A total of 15 placental swabs gave positive results for SARS-CoV-2 ribonucleic acid (RNA) on the fetal side of the placenta. SARS-CoV-2 RNA was found in seven breastmilk samples. One umbilical cord sample was positive for SARS-CoV-2. One amniotic fluid sample tested positive for SARS-CoV-2. Conclusions: This study presents some evidence to support the potential of congenital, intrapartum, and postnatal maternal-fetal-neonatal SARS-CoV-2 infections during the COVID-19 pandemic. Mothers should follow recommendations including wearing a facemask and hand washing before and after breastfeeding.

Late-life depression is a highly prevalent mental health condition with devastating consequences even from its earliest stages. Alterations in physiological functions, such as inflammatory and metabolic, have been described in patients with depression. However, little is known on the association between depression symptom course and metabolic and inflammation dysregulation. This study aimed to depict the course of depression symptoms while ageing, taking into consideration inter-individual heterogeneity. Moreover, it intended to study the associations between inflammatory and metabolic risk profiles and symptom trajectories. To do so, data from 13,203 adults aged 50–90 years (52.75% women; mean age at baseline = 65.07, SD = 10.00) were used. Blood sample and blood pressure measures were taken from 1536 participants (56.58% women; mean age at baseline = 61.73 years, sd = 7.64). Depression symptoms were assessed every two years across a 10-year follow-up. Trajectories were identified by means of latent class mixed modelling. Inflammation and metabolic risk profile scores were obtained from plasma and diagnostic-based indicators in the follow-up, using a robust latent-factor approach. Multigroup modelling was used to study the associations between the profiles and symptom trajectories. As a result, three heterogeneous trajectories of symptoms were identified (low-symptom, moderate-symptom and high-symptom trajectory). Participants depicting a high-symptom trajectory showed the greatest inflammation profile score and high metabolic risk. Moderate-symptom trajectory was also related to high inflammation and metabolic risk. To sum up, at-risk trajectories of symptoms were associated with high inflammation and risk of metabolic diseases. This study provides valuable evidence to advance personalised medicine and mental health precision, considering person-specific profiles and physiological concomitants.

Background This study aimed at depicting the course of depression symptoms over the old age, with a special interest in a) uncovering its relationships with sociodemographic and health-related factors; b) analysing its predictive role on healthy-ageing outcomes later in life. Methods The sample comprised 8317 older adults (46.02% men) from the English Longitudinal Study of Ageing. Robust structural equation modelling was used to identify symptom trajectories and their relationships with time-varying factors. Trajectory class and covariates were used to predict outcomes (quality of life, satisfaction with life, and daily living functioning) in a 2-year follow-up. Results Three trajectory classes (so-called, normative, subclinical, chronic symptom trajectories) were identified for both sexes. Rising hearing difficulties and history of psychiatric problems were consistently associated with the chronic symptom trajectory. Lower education level, history of psychiatric problems, and increasing visual difficulties were connected with the subclinical trajectories. Finally, participants with either a subclinical or a chronic symptom trajectory showed worse outcomes than the remaining participants in the follow-up. Conclusion This study highlighted the presence of varying courses of depression symptoms (each showing some distinctive features from other another) over the old age, pointing to some relevant implications for clinical assessment and treatment prescription.

Diana Lüftner,1 Veronica Dell’Acqua,2 Frédéric Selle,3 Ahmed Khalil,3 Maria Cristina Leonardi,2 Alejandro De La Torre Tomás,4 George Shenouda,5 Jesus Romero Fernandez,4 Roberto Orecchia,2,6 Dominique Moyal,7 Sophie Seité7 1Department of Hematology, Oncology and Tumor Immunology, Charité University Hospital Berlin, Campus Benjamin Franklin, Berlin, Germany; 2Department of Radiotherapy, IEO, European Institute of Oncology IRCCS, Milan, Italy; 3Tenon Hospital, Paris, France; 4Puerta de Hierro Hospital, Madrid, Spain; 5McGill Hospital, Montreal, Canada; 6Milan University, Milan, Italy; 7La Roche-Posay Dermatological Laboratory, Levallois-Perret, France Introduction: The purpose of this multicenter, prospective, observational, open-label study was to evaluate the use and tolerability of dermo-cosmetic products in preventing skin reactions associated with cancer treatments. Patients and methods: A 12-product kit was supplied to patients before chemotherapy began and was to be used throughout the treatment phase. Cutaneous adverse events were evaluated at each treatment session. Physicians evaluated skin reactions (edema, erythema, dryness, desquamation, pigmentation disorders, and cracks) and gave their opinion on the skin benefit for patients at the end of the study. Patients also evaluated the product benefit using the Patient Benefit Index (PBI) questionnaire. Results were analyzed by subgroups of casual and regular users, based on number and frequency of products used. Results: A total of 147 patients were enrolled in cancer services in Germany, France, Italy, Spain, and Canada. Mean age was 59 years with 71% being female. Product tolerance on whole body was rated good to excellent for at least 89% of the patients for each product. Aggravated skin reactions during the study were reported more frequently by casual users than regular users (39.5% versus 22%; p=0.029). Similarly, casual users reported more erythema aggravation (p=0.02) and desquamation (p=0.03) than regular users. PBI >1 was reported for 95.5% of patients and regular users had significantly higher scores than casual users (p=0.049). Discussion: Overall, the 12-product kit was very well tolerated, with regular users reporting benefits more frequently than casual users. Results support international recommendations to use appropriate skin care products to minimize the impact of cutaneous reactions associated with chemotherapy. Keywords: dermocosmetic, dermatological toxicity, skin side effect, skin reaction, palliative care

Background & Aims Many pediatric patients with acute liver failure (PALF) do not receive a specific diagnosis (such as herpes simplex virus or Wilson disease or fatty acid oxidation defects)—they are left with an indeterminate diagnosis and are more likely to undergo liver transplantation, which is contraindicated for some disorders. Strategies to facilitate complete diagnostic testing should increase identification of specific liver diseases and might reduce liver transplantation. We investigated whether performing recommended age-specific diagnostic tests (AS-DTs) at the time of hospital admission reduces the percentage PALFs with an indeterminate diagnosis. Methods We performed a multinational observational cohort study of 658 PALF participants in the United States and Canada, enrolled at 10 medical centers, during 3 study phases from December 1999 through December 2014. A learning collaborative approach was used to implement AS-DT using an electronic medical record admission order set at hospital admission in phase 3 of the study. Data from 10 study sites participating in all 3 phases were compared before (phases 1 and 2) and after (phase 3) diagnostic test recommendations were inserted into electronic medical record order sets. Results The percentage of subjects with an indeterminate diagnosis decreased significantly between phases 1–2 (48.0%) and phase 3 (to 30.8%) (P = .0003). The 21-day cumulative incidence rates for liver transplantation were significantly different among phase 1 (34.6%), phase 2 (31.9%), and phase 3 (20.2%) (P = .030). The 21-day cumulative incidence rates for death did not differ significantly among phase 1 (17.9%), phase 2 (11.9%), and phase 3 (11.3%) (P = .20). Conclusions In a multinational study of children with acute liver failure, we found that incorporating diagnostic test recommendations into electronic medical record order sets accessed at time of admission reduced the percentage with an indeterminate diagnosis that may have reduced liver transplants without increasing mortality. Widespread use of this approach could significantly enhance care of acute liver failure in children.

To explore sleep-related problems reported by patients with cancer prior to undergoing radiotherapy, and to analyse the effect of cancer severity, history of treatment and psychosomatic symptomatology on these problems.A descriptive cross-sectional study was conducted. One hundred and five patients with cancer were evaluated prior to radiotherapy. The primary endpoint was the sleep problem score measured by a self-rated version of the Oviedo Sleep Questionnaire. Secondary variables were impact of pain on sleep, anxiety and asthenia.Patients reported important levels of insomnia and hypersomnia. Insomnia-related problems were significantly higher in patients with more-severe disease (P 0.05), and led to higher levels of hypnotic drug intake. Prior chemotherapy was significantly associated with hypersomnia-related problems (P 0.05). Anxiety was significantly associated with both sleep-related problems.Sleep problems are significant among patients with cancer prior to undergoing radiotherapy, and were found to be associated with progression of cancer, prior treatments and other psychosomatic symptoms (e.g. anxiety). Sleep problems within this context must be explored to provide adequate guidelines to palliate their effects on quality of life.

Background Premature infants are exposed to high levels of noise in the neonatal intensive care unit (NICU). Purpose This study evaluated the effect of a relaxing music therapy intervention composed by artificial intelligence on respiratory rate, systolic and diastolic blood pressure, and heart rate. Methods A double-blind, randomized, controlled trial was conducted in the NICUs of 2 general public hospitals in Andalusia, Spain. Participants were 17 healthy premature infants, randomly allocated to the intervention group or the control group (silence) at a 1:1 ratio. To be included in the study, the subjects were to be 32 to 36 weeks of gestation at birth (M= 32.33; SD = 1.79) and passed a hearing screening test satisfactorily. The intervention lasted 20 minutes, 3 times a day for 3 consecutive days, while infants were in the incubator. Infants' heart rate, respiratory rate, and blood pressure were assessed before and after each intervention session. Results After each session, the respiratory rate decreased in the experimental group (main between-groups effect (F1,13 = 6.73, P = .022, ηpartial = 0.34). Across the sessions, the heart rate increased in the control group (main between-groups effect, F1,11 = 5.09, P = .045, ηpartial = 0.32). Implications for research Future studies can use this music intervention to assess its potential effects in premature infants. Implications for practice Nurses can apply the relaxing music intervention presented in this study to ameliorate the impact of the stressful environment on premature infants.

To determine health-related quality of life (HRQoL) and neurocognitive impairment in survivors of pediatric acute liver failure (PALF).A longitudinal prospective study was conducted. At 6 and 12 months after PALF presentation, surveys of HRQoL were completed for 2- to 19-year-olds and executive functioning for ages 2-16 years. At 12 months, patients 3-16 years of age completed neurocognitive testing. HRQoL scores were compared with a healthy, matched sample. Neurocognitive scores were compared with norms; executive functioning scores were examined categorically.A total of 52 parent-report HRQoL surveys were completed at 6 months, 48 at 12 months; 25 patients completed neurocognitive testing. The median age at 6 months was 7.9 years (range 3.5-15.0), and final diagnosis was indeterminate for 46.2% (n = 24). Self and parent-report on Pediatric Quality of Life Inventory Generic and Multidimensional Fatigue scales fell below the healthy sample at 6 months and 12 months (almost all P .001). Children reported lower mean scores on cognitive fatigue at 12 months (60.91 ± 22.99) compared with 6 months (73.61 ± 27.49, P = .006) . The distribution of Behavior Rating Inventory of Executive Function scores was shifted downward on parent-report (preschool) for all indices at 6 months (n = 14, P ≤ .003); Global Executive Composite and Emergent Metacognition at 12 months (n = 10, P = .03). Visual Motor Integration (VMI-6) Copying (mean = 90.3 ± 13.8, P = .0002) and VMI-6 Motor Coordination (mean = 85.1 ± 15.2 P = .0002) fell below norms, but full scale IQ (Wechsler Scales) and Attention (Conners' Continuous Performance Test) did not.Survivors of PALF appear to show deficits in motor skills, executive functioning, HRQoL, and evidence for worsening cognitive fatigue from 6 to 12 months following PALF presentation.

Background Individuals diagnosed with diabetes mellitus have an increased risk of cardiovascular disease, often leading to premature morbidity and mortality. As the number of youth developing T1D and T2D continues to grow, early onset predisposes patients to a longer burden of disease and earlier onset of cardiovascular complications. Early identification and effective management and treatment of risk factors can lead to decreased cardiovascular events and improved quality of life. Objective In this study, we describe the prevalence of CVD risk factors in children with diabetes. Results 274 subjects were included in this study, all > 1 year since the time of diagnosis. 134 participants were male (49%). Mean age was 13.7 years (males); 12.8 years (females). subjects averaged 4 diabetes-related visits per year. At the time of their most recent clinic visit, 33% of subjects had a HbA1c 10%. Greater than 50% of subjects were overweight or obese. A significant number of subjects were found to have dyslipidemia, and elevated blood pressure was common. Discussion CVD risk factors are common in children with diabetes mellitus. Good glycemic control, early identification, and effective life-long management of all CVD risk factors may help decrease the high rate of premature morbidity and mortality in diabetes.

Background: Breakthrough pain is a major problem and a source of distress in patients with cancer. We hypothesized that health care professionals may benefit from a real-time mobile app to assist in the diagnosis and monitoring of breakthrough cancer pain (BTcP). Objective: This study aimed to test the usability, acceptability, and usefulness in real-world practice of the mobile App INES·DIO developed for the management of patients with BTcP. Methods: This study consisted of a survey of a multidisciplinary sample of 175 physicians who evaluated the mobile app after testing it with 4 patients with BTcP each (for a total of 700 patients). The digital profile of the physicians, use of the different resources contained in the app, usefulness of the resources, acceptability, usability, potential improvements, intention to use, and additional resources to add were recorded. Results: Of the 175 physicians, 96% (168/175) were working in public hospitals. They had an average of 12 (SD 7) years of experience in BTcP and almost all (174/175, 99.43%) had an active digital profile. The Eastern Cooperative Oncology Group and Karnofsky performance scales, the Visual Analogue Scale, and the Davies algorithm to diagnose BTcP were the most frequently used tools with patients and were assessed as very useful by more than 80% (140/175) of physicians. The majority (157/175, 90%) answered that App INES·DIO was well designed and 94% (165/175) would probably or very probably recommend it to other colleagues. More than two-thirds indicated that the report provided by the app was worth being included in patients’ clinical records. The most valued resource in the app was the recording of the number, duration, and intensity of pain flares each day and baseline pain control to enhance diagnosis of BTcP. Additional patient-oriented cancer pain educational content was suggested for inclusion in future versions of App INES·DIO. Conclusions: Our study showed that App INES·DIO is easy to use and useful for physicians to help diagnose and monitor breakthrough pain in patients with cancer. Participants suggested the implementation of additional educational content about breakthrough pain. They agreed on the importance of adding new clinical guidelines/protocols for the management of BTcP, improving their communication skills with patients, and introducing an evidence-based video platform that gathers new educational material on BTcP.

Background Incidence of human papillomavirus (HPV)-related oropharyngeal carcinomas is increasing worldwide. The purpose of this study was to report the incidence in our region, and to determine the influence of HPV status on survival among a heavy smoking population. Methods p16 expression was analyzed in 102 patients with stage II to IV treated with chemoradiation. Overall survival (OS), locoregional control, and disease-free survival (DFS) were compared for HPV+ and HPV− status. Results The majority of patients were smokers (86%). p16 positivity was found in 26.7%. Patients who were HPV+ were younger (56 vs 59 years old; p = .052). No differences were observed regarding tumor stage, sex, or smoking between HPV+ and HPV−. Three-year OS was 67.4% for patients who were HPV+ versus 49.7% for HPV− (hazard ratio [HR], 0.55; p = .095). Conclusion Incidence of HPV-related oropharyngeal carcinoma in Spain is similar to that reported in other European countries. In this sample of heavy smokers, we observed a nonsignificant trend for better outcomes in patients who were HPV+. © 2013 Wiley Periodicals, Inc. Head Neck 36: 782–786, 2014

A multivariate analysis was carried out in 492 patients with metastatic neck disease from squamous cell carcinoma to determine the influence of clinical and therapeutic factors on survival, local and regional control, and distant metastases. After radiation treatment with radical intent, recurrence at the primary site was the most frequent site of treatment failure (20% of cases), followed by distant metastases (14% of the cases), whereas isolated neck recurrences occurred in only 7% of the patients. The most significant factors influencing survival were primary tumor site, node fixation, N-stage, T-stage, and number of lymphatic chains. The most significant factors influencing local control were primary site, T-stage, and node fixation. Significant factors influencing regional control were radiation therapy volume, primary tumor site, node fixation, and node location (upper and lower neck). Significant factors influencing distant control were N-stage, number of nodes, and number of involved lymphatic chains.

Chordomas are tumors with a bad prognosis, because of their location, local aggressiveness and high rate of local relapse. Despite of be benign tumors, they have certain capacity of metastasize and a clinical evolution that results interesting. When we analyzed our series with 35 chordomas studied and treated between 1975 and 2002, we found three patients that experienced a systemic dissemination.

To investigate the heterogeneity in clinical course among those with pediatric acute liver failure (PALF) of indeterminate disease etiology.We studied participants enrolled in the PALF registry study with indeterminate final diagnosis. Growth mixture modeling was used to analyze participants' international normalized ratio, total bilirubin, and hepatic encephalopathy trajectories in the first 7 days following enrollment. Participants with at least 3 values for 1 or more of the measurements were included. We examined the association between the resulting latent subgroup classification with participants' characteristics and disease outcomes. Data from participants with PALF of specified etiologies were used to investigate the potential diagnostic value of the latent subgroups.In this sample of 380 participants with indeterminate final diagnosis, 115 (30%) experienced mild and quickly improving disease trajectories and another 48 (13%) started with severe disease but improved by day 7. The majority of participants (216, 57%) had disease trajectories that worsened over time. The identified patterns of disease trajectories are predictive of outcome (P.001). The trajectory patterns are associated with the underlying disease etiology (P.001) for the 488 participants with PALF of specified etiologies.The clinical courses of participants with PALF of indeterminate disease etiology exhibit distinct trajectory patterns, which have important prognostic and potentially diagnostic value.

Objectives In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. Study design A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months. Results A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy. Conclusions A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

The concurrent use of erythropoietin beta (EPO) and radiotherapy in head and neck cancer patients has been reported by Henke et al (Lancet 2003; 362:1255–60) to correct anemia and impair cancer control. Due to the potential impact in daily clinical practice of this information a systematic critical review of the mentioned article was performed. Authors selected 10 arguments to question the contents regarding methodological and statistical aspects of the trial, and added 14 comments of controversy in more basic scientific concepts mentioned in the text as published. The panel including epidemiologist and radiation oncologists with expertise in clinical research concluded with 5 additional remarks recommending caution in interpretation of these results in terms of changes in daily practice of anemic patients support and advising not to use EPO at experimental doses or after reaching physiological concentrations of hemoglobin.

Hodgkin's disease (HD) is a curable tumoral disease. However, there are groups of patients who suffer relapse and the identification of prognostic factors and the adaptation of treatments to individual risk is one the lines of investigation in this disease. A study was performed on 526 patients diagnosed of HD in our hospital between January 1967 and September 2001. An analysis was made of the most important variables in terms of both disease-free and overall survival. Overall survival in this series of patients was 94% at 2 years, 86% at 5 years, 76% at 10 years and 72% at 15 years. Median survival was 249 months. Factors influencing poor prognosis in the overall survival were: male gender (P < 0.0001), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.0001), B symptoms (P < 0.0001), spleen involvement at diagnosis (P = 0.003), no complete remission after first line treatment (P < 0.0001), and more than 30 years-of-age (P < 0.0001). Disease free survival was 83% at 2 years and 68% at 5 years although without reaching the mean follow-up. The disease free survival study revealed the following risk factors: male gender (P = 0.02), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.001), B symptoms (P < 0.001), extranodal or splenic involvement (P < 0.05), and no complete remission after first line treatment (P < 0.0001). The result of treatment optimization is that some factors that were considered to indicate a poor prognosis have disappeared, and that others which are useful have appeared and allow us to establish groups with differing risks of relapse and who could be candidates for differentiated treatments.

The presentation of intracranial metastases from Hodgkin's lymphoma is an infrequent event that worsens clinical outcome. A case of Hodgkin's lymphoma relapse in the cerebellum is described in a 70-year-old woman with a previously treated stage IVA Hodgkin's lymphoma. Diagnostic workup and treatment strategies for central nervous system relapses are reviewed and discussed. A combination of surgery, radiotherapy and occasionally chemotherapy remains the most appropriate approach to intracranial Hodgkin's lymphoma.

Purpose: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT) plus low-dose leucovorin administered concomitantly with pelvic irradiation in patients with unresectable or recurrent rectal cancer. Methods and Materials: Thirty-five patients (22 with primary unresectable tumors and 13 with locally recurrent tumors) were enrolled in the trial. Thirty-five patients were evaluable for toxicity and 32 of these were evaluable for clinical response. Patients received 300 mg/m 2 /day UFT and 30 mg/day leucovorin on days 8–35 concomitantly with pelvic radiotherapy, to a total dose of 45 Gy. Results: Eight of the 35 (23%) patients developed Grade 3 diarrhea and were treated with radiotherapy alone after this event. Of the 22 patients with unresectable primary tumors, 17 underwent surgery, and resection was feasible in 15 cases (88%). Of the 32 patients evaluable for clinical response, 4 (13%) had a complete clinical response (CR) and 22 (69%) a partial response (PR). A complete pathologic response was observed in 3 cases (18%) and, a PR in 11 cases (65%). Conclusion: The response rates achieved with this schedule seem comparable to those obtained with 5-FU and radiotherapy. These results warrant further evaluation of this combination in patients with unresectable or locally advanced tumors.

Transformations that take into account the characteristics of balloon motion and wave propagation to infer the “real” wavelengths and frequencies from the “apparent” ones measured during sounding are derived. To estimate the differences that may arise in the observations of internal gravity waves, a statistical relation between their wavelength and period recently found from theory and experiment is applied. It is shown that it may not be possible to determine from each apparent datum a unique real value, because up to four different transformations may be applicable for each experimental datum of wavelength or frequency. However, under certain conditions this ambiguity can be removed. The omission of the appropriate transformation may lead one to seriously misinterpret the data.