Cause of death estimation from verbal autopsies: is the open response redundant or synergistic?

Civil registration and vital statistics systems capture birth and death events to compile vital statistics and to provide legal rights to citizens. Vital statistics are a key factor in promoting public health policies and the health of the population. Medical certification of cause of death is the preferred source of cause of death information. However, two thirds of all deaths worldwide are not captured in routine mortality information systems and their cause of death is unknown. Verbal autopsy is an interim solution for estimating the cause of death distribution at the population level in the absence of medical certification. A Verbal Autopsy (VA) consists of an interview with the relative or the caregiver of the deceased. The VA includes both Closed Questions (CQs) with structured answer options, and an Open Response (OR) consisting of a free narrative of the events expressed in natural language and without any pre-determined structure. There are a number of automated systems to analyze the CQs to obtain cause specific mortality fractions with limited performance. We hypothesize that the incorporation of the text provided by the OR might convey relevant information to discern the CoD. The experimental layout compares existing Computer Coding Verbal Autopsy methods such as Tariff 2.0 with other approaches well suited to the processing of structured inputs as is the case of the CQs. Next, alternative approaches based on language models are employed to analyze the OR. Finally, we propose a new method with a bi-modal input that combines the CQs and the OR. Empirical results corroborated that the CoD prediction capability of the Tariff 2.0 algorithm is outperformed by our method taking into account the valuable information conveyed by the OR. As an added value, with this work we made available the software to enable the reproducibility of the results attained with a version implemented in R to make the comparison with Tariff 2.0 evident

The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation.

Metastatic cancer cells have the ability to both degrade and migrate through the extracellular matrix (ECM). Invasiveness can be correlated with the presence of dynamic actin-rich membrane structures called podosomes or invadopodia. We showed previously that the adaptor protein tyrosine kinase substrate with five Src homology 3 domains (Tks5)/Fish is required for podosome/invadopodia formation, degradation of ECM, and cancer cell invasion in vivo and in vitro. Here, we describe Tks4, a novel protein that is closely related to Tks5. This protein contains an amino-terminal Phox homology domain, four SH3 domains, and several proline-rich motifs. In Src-transformed fibroblasts, Tks4 is tyrosine phosphorylated and predominantly localized to rosettes of podosomes. We used both short hairpin RNA knockdown and mouse embryo fibroblasts lacking Tks4 to investigate its role in podosome formation. We found that lack of Tks4 resulted in incomplete podosome formation and inhibited ECM degradation. Both phenotypes were rescued by reintroduction of Tks4, whereas only podosome formation, but not ECM degradation, was rescued by overexpression of Tks5. The tyrosine phosphorylation sites of Tks4 were required for efficient rescue. Furthermore, in the absence of Tks4, membrane type-1 matrix metalloproteinase (MT1-MMP) was not recruited to the incomplete podosomes. These findings suggest that Tks4 and Tks5 have overlapping, but not identical, functions, and implicate Tks4 in MT1-MMP recruitment and ECM degradation.Peer reviewe

The novel adaptor protein Tks4 (SH3PXD2B) is required for functional podosome formation.

Metastatic cancer cells have the ability to both degrade and migrate through the extracellular matrix (ECM). Invasiveness can be correlated with the presence of dynamic actin-rich membrane structures called podosomes or invadopodia. We showed previously that the adaptor protein tyrosine kinase substrate with five Src homology 3 domains (Tks5)/Fish is required for podosome/invadopodia formation, degradation of ECM, and cancer cell invasion in vivo and in vitro. Here, we describe Tks4, a novel protein that is closely related to Tks5. This protein contains an amino-terminal Phox homology domain, four SH3 domains, and several proline-rich motifs. In Src-transformed fibroblasts, Tks4 is tyrosine phosphorylated and predominantly localized to rosettes of podosomes. We used both short hairpin RNA knockdown and mouse embryo fibroblasts lacking Tks4 to investigate its role in podosome formation. We found that lack of Tks4 resulted in incomplete podosome formation and inhibited ECM degradation. Both phenotypes were rescued by reintroduction of Tks4, whereas only podosome formation, but not ECM degradation, was rescued by overexpression of Tks5. The tyrosine phosphorylation sites of Tks4 were required for efficient rescue. Furthermore, in the absence of Tks4, membrane type-1 matrix metalloproteinase (MT1-MMP) was not recruited to the incomplete podosomes. These findings suggest that Tks4 and Tks5 have overlapping, but not identical, functions, and implicate Tks4 in MT1-MMP recruitment and ECM degradation.Peer reviewe

Efectos de un programa de estiramientos FNP sobre el salto y la flexibilidad en jugadores profesionales de fútbol sala

The purpose of this study was to examine the effects of a stretching program with the contraction-relaxation-agonist-contraction technique (CRAC) on jumping performance (JP) and range of motion (ROM). A total of 21 elite futsal players participated in the present study. Participants were assigned to a control group (CG) and an experimental group (EG) according to their jumping ability. Before and after the intervention, the JP and ROM of hip flexion with the extended knee (FCRE) and dorsi-flexion of the ankle (DFTRE) were measured. For the measurement of the JP and the ROM, a contact platform and an ISOMED inclinometer were used, respectively. The EG performed a stretching program in the hamstrings and triceps sural for 4 weeks with a weekly frequency of 5 days. The players significantly increased the FCRE ROM (p = 0.02) with strong effect (hp2 = 0.730) and ROM DFTRE (p = 0.01) with moderate effect (hp2 = 0.546), of the values ​​of CMJ (p = 0.03) with strong effect (hp2 = 0.650) and of the values ​​of index of utilization of the elastic capacity [IACE] (p = 0.04) with strong effect (hp2 = 0,742) in the EG after the stretching. The CG players significantly increased the performance in the CMJ ​​(p = 0.02) with moderate effect (hp2 = 0.519) and IACE (p = 0.04) with moderate effect (hp2 = 0.548); in addition, significant differences were observed in the values ​​of IACE (p = 0.02) between both groups. The results of this study allow us to conclude that a training period with the CRAC technique improves ROM and JP in professional futsal players.El objetivo de este estudio fue comprobar los efectos de un programa de estiramiento con la técnica contracción-relajación-agonista-contracción (CRAC) sobre la capacidad de salto (CS) y el rango de movimiento (ROM). Un total de 21 jugadores de élite de fútbol sala participaron en el presente trabajo. Los participantes fueron asignados a un grupo control (GC) y a un grupo experimental (GE) según su CS. Antes y después de la intervención se midió la CS y el ROM de flexión de cadera con la rodilla extendida (FCRE) y dorsi-flexión de tobillo (DFTRE). Para la medición del CS y del ROM se utilizó una plataforma de contacto y un inclinómetro ISOMED, respectivamente. El GE realizó un programa de estiramientos en los isquiosurales y tríceps sural durante 4 semanas con una frecuencia semanal de 5 días. Los jugadores aumento significativamente el ROM FCRE (p = 0,02) con efecto fuerte (hp2 = 0,730) y ROM DFTRE (p = 0,01) con efecto moderado (hp2 = 0,546), de los valores de CMJ (p = 0,03) con efecto fuerte (hp2 = 0,650) y de los valores de índice de aprovechamiento de la capacidad elástica [IACE] (p = 0,04) con efecto fuerte (hp2 = 0,742) en el GE después de los estiramientos. Los jugadores del GC aumentaron significativamente el rendimiento en el CMJ (p = 0,02) con efecto moderado (hp2 = 0,519) e IACE (p = 0,04) con efecto moderado (hp2 = 0,548); además, se observaron diferencias significativas en los valores de IACE (p = 0,02) entre ambos grupos. Los resultados de este estudio permiten concluir que un periodo de entrenamiento con el método CRAC mejora el ROM y la CS en jugadores profesionales de fútbol sala

IGR J19552+0044: A new asynchronous short period polar: "Filling the gap between intermediate and ordinary polars"

Based on XMM--Newton X-ray observations IGR J19552+0044 appears to be either a pre-polar or an asynchronous polar. We conducted follow-up optical observations to identify the sources and periods of variability precisely and to classify this X-ray source correctly. Extensive multicolor photometric and medium- to high-resolution spectroscopy observations were performed and period search codes were applied to sort out the complex variability of the object. We found firm evidence of discording spectroscopic (81.29+/-0.01m) and photometric (83.599+/-0.002m) periods that we ascribe to the white dwarf (WD)\ spin period and binary orbital period, respectively. This confirms that IGR J19552+0044 is an asynchronous polar. Wavelength-dependent variability and its continuously changing shape point at a cyclotron emission from a magnetic WD with a relatively low magnetic field below 20 MG. The difference between the WD spin period and the binary orbital period proves that IGR J19552+0044 is a polar with the largest known degree of asynchronism (0.97 or 3%).Comment: 9 pages, 10 figures, A&A accepte

Association of CSF sTREM2, a marker of microglia activation, with cholinergic basal forebrain volume in major depressive disorder

BACKGROUND: Inflammatory mechanisms are believed to contribute to the manifestation of major depressive disorder (MDD). Central cholinergic activity may moderate this effect. Here, we tested if volume of the cholinergic basal forebrain is associated with cerebrospinal fluid (CSF) levels of sTREM2 as a marker of microglial activation in people with late life MDD. METHODS: Basal forebrain volume was determined from structural MRI scans and levels of CSF sTREM2 with immunoassay in 29 people with late-life MDD and 20 healthy older controls at baseline and 3 years follow-up. Associations were determined using Bayesian analysis of covariance. RESULTS: We found moderate level of evidence for an association of lower CSF levels of sTREM2 at 3 years follow up with MDD (Bayes factor in favor of an effect = 7.9). This level of evidence prevailed when controlling for overall antidepressant treatment and CSF levels of markers of AD pathology, i.e., Aβ42/Aβ40, ptau181 and total tau. Evidence was in favor of absence of an effect for baseline levels of CSF sTREM2 in MDD cases and for baseline and follow up data in controls. LIMITATIONS: The sample size of repeated CSF examinations was relatively small. Therefore, we used Bayesian sequential analysis to assess if effects were affected by sample size. Still, the number of cases was too small to stratify effects for different antidepressive treatments. CONCLUSIONS: Our data agree with the assumption that central cholinergic system integrity may contribute to regulation of microglia activity in late-life MDD

Validity and reliability of the new Basic Functional Assessment protocol (BFA)

The global evaluation of motion patterns can examine the synchrony of neuromuscular control, range of motion, strength, resistance, balance and coordination needed to complete the movement. Visual assessments are commonly used to detect risk factors. However, it is essential to define standardized field-based tests that can evaluate with accuracy. The aims of the study were to design a protocol to evaluate fundamental motor patterns (FMP), and to analyze the validity and reliability of an instrument created to provide information about the quality of movement in FMP. Five tasks were selected: Overhead Squat (OHS); Hurdle Step (HS); Forward Step Down (FSD); Shoulder Mobility (SM); Active Stretching Leg Raise (ASLR). A list of variables was created for the evaluation of each task. Ten qualified judges assessed the validity of the instrument, while six external observers performed inter-intra reliability. The results show that the instrument is valid according to the experts’ opinion; however, the reliability shows values below those established. Thus, the instrument was considered unreliable, so it is recommended to repeat the reliability process by performing more training sessions for the external observers. The present study creates the basic functional assessment (BFA), a new protocol which comprises five tasks and an instrument to evaluate FMP

Evidence of upregulation of the cholinergic anti-inflammatory pathway in late-life depression

BACKGROUND: Decreased cholinergic tone associated with increased proinflammatory cytokines has been observed in several human diseases associated with low-grade inflammation. We examined if this attenuated cholinergic anti-inflammatory pathway (CAP) mechanism contributed to increased neuroinflammation observed in depression. METHODS: We measured cerebrospinal fluid (CSF) cholinergic markers (AChE and BChE activities) in 28 individuals with longstanding late-life major depression (LLMD) and 19 controls and their relationship to central and peripheral levels of pro-inflammatory cytokines (IL-6 and IL-8). Additionally, we examined if these cholinergic indices were related to CSF markers of microglial activation and neuroinflammation (sTREM2 and complement C3). RESULTS: Compared with controls, LLMD patients had a significant reduction in CSF BChE levels. Lower CSF BChE and AChE activities were associated with lower CSF markers of microglial and neuroinflammation (sTREM2 and C3). In addition, in LLMD patients we found an inverse relationship between peripheral marker of inflammation (plasma IL-6) and CSF BChE and AChE levels. CONCLUSIONS: Our results suggest an upregulation of the CAP mechanism in LLMD with an elevation in peripheral markers of inflammation and concomitant reduction in markers of glial activation associated with a higher cholinergic tone. Future studies should confirm these findings in a larger sample including individuals with acute and more severe depressive episodes and across all ages

Complement component 3 levels in the cerebrospinal fluid of cognitively intact elderly individuals with major depressive disorder

Late-life major depression (LLMD) is a risk factor for the development of mild cognitive impairment and dementia, including Alzheimer's disease (AD) and vascular dementia. Immune dysregulation and changes in innate immune responses in particular, have been implicated in the pathophysiology of both LLMD and AD. Complement system, a key component of the innate immune mechanism, is known to play an important role in synaptic plasticity and cognitive functions. However, its role in LLMD remains unknown. In the present study, we examined the levels of complement component 3 (C3, the convergence point of all complement activation pathways) in the cerebrospinal fluid (CSF) of elderly depressed subjects compared to healthy controls; as well as the relationship of CSF C3 levels with amyloid-beta (Aβ42 and Aβ40), total tau (T-tau) and phosphorylated tau (P-tau) proteins and cognition scores. CSF was obtained from 50 cognitively intact volunteers (major depression group, N = 30; comparison group, N = 20) and analyzed for levels of C3 by ELISA. C3 levels were marginally lower in the major depression group relative to the comparison group. We did not find any significant association of C3 with the AD biomarkers Aβ42 reflecting plaque pathology, P-tau related to tau pathology or the neurodegeneration biomarker T-tau. In contrast, C3 was positively correlated with CSF Aβ40, which may reflect Aβ deposition in cerebral vessel walls. We observed a negative correlation between C3 levels and Total Recall on the Buschke Selective Reminding Test (BSRT) for memory performance in the depressed subjects when controlling for education. This initial evidence on C3 status in LLMD subjects may have implications for our understanding of the pathophysiology of major depression especially in late life