Generalized low-density codes with BCH constituents for full-diversity near-outage performance

A new graph-based construction of generalized low density codes (GLD-Tanner) with binary BCH constituents is described. The proposed family of GLD codes is optimal on block erasure channels and quasi-optimal on block fading channels. Optimality is considered in the outage probability sense. Aclassical GLD code for ergodic channels (e.g., the AWGN channel,the i.i.d. Rayleigh fading channel, and the i.i.d. binary erasure channel) is built by connecting bitnodes and subcode nodes via a unique random edge permutation. In the proposed construction of full-diversity GLD codes (referred to as root GLD), bitnodes are divided into 4 classes, subcodes are divided into 2 classes, and finally both sides of the Tanner graph are linked via 4 random edge permutations. The study focuses on non-ergodic channels with two states and can be easily extended to channels with 3 states or more.

Intrauterine growth restriction and absent or reverse end-diastolic blood flow in umbilical artery (Doppler class II or III): A retrospective study of short- and long-term fetal morbidity and mortality.

OBJECTIVE: Absent or reverse end-diastolic flow (Doppler II/III) in umbilical artery is correlated with poor perinatal outcome, particularly in intrauterine growth restricted (IUGR) fetuses. The optimal timing of delivery is still controversial. We studied the short- and long-term morbidity and mortality among these children associated with our defined management. STUDY DESIGN: Sixty-nine IUGR fetuses with umbilical Doppler II/III were divided into three groups; Group 1, severe early IUGR, no therapeutic intervention (n = 7); Group 2, fetuses with pathological biophysical profile, immediate delivery (n = 35); Group 3, fetuses for which expectant management had been decided (n = 27). RESULTS: In Group 1, stillbirth was observed after a mean delay of 6.3 days. Group 2 delivered at an average of 31.6 weeks and two died in the neonatal period (6%). In Group 3 after a mean delay of 8 days, average gestational age at delivery was 31.7 weeks; two intra uterine and four perinatal deaths were observed (22%). Long-term follow-up revealed no sequelae in 25/31 (81%) and 15/18 (83%), and major handicap occurred in 1 (3%) and 2 patients (11%), respectively, for Groups 2 and 3. CONCLUSION: Fetal mortality was observed in 22% of this high risk group. After a mean period of follow-up of 5 years, 82% of infants showed no sequelae. According to our management, IUGR associated with umbilical Doppler II or III does not show any benefit from an expectant management in term of long-term morbidity.

Maternal mortality from hemorrhage in the State of Santa Catarina, Brazil

Hemorrhage represents a set of causes that focuses on women during the pregnancy and puerperal period, and that, with improper attention, results in death. The authors aimed to analyze maternal deaths related to hemorrhage that occurred in the state of Santa Catarina, Brazil. The data were obtained from the Mortality Information System and Live Births Information System from the Brazilian Ministry of Health. This was a descriptive study, in which 491 maternal deaths that occurred in the period 1997-2010 were analyzed. Of these, 61 were related to hemorrhage, corresponding to 12.42%; postpartum hemorrhage was the most prevalent cause, with 26 deaths, followed by placental abruption with 15, representing 67.21% of the cases. The maternal mortality from hemorrhage is a public health problem in the state of Santa Catarina, due to its high prevalence and the fact that its underlying causes are preventable.

Hospitalizations leading causes for maternal disorders

Presenting the rates of obstetric admissions of women living in Paraná in 2010.Method: A descriptive study in which the admission information of the hospital system of the Unified Health System was analyzed. Data from women aged between 10 to 49 years available on the DATASUS website were analyzed, using percentage and according to primary diagnosis, age and Regional Health area.Results: The Rate of Obstetric Complications (RtOC) was 38%, increasing with the age of women. Complications of labor and delivery (10.5%), and pregnancy with abortive outcome (9.1%) were the diagnoses with highest RtOC. The RtOC ranged between 8.4% in Telêmaco Borba, until 62.6% in Ponta Grossa.Conclusion: The healthcare team should monitor the rates of admissions for obstetric complications as these indicate the quality of health care of women, mainly focused on labor, delivery and women of older age.


Epuration extrarénale continue pour l'insuffisance rénale aiguë aux soins intensifs [Continuous renal replacement therapy for acute kidney injury].

Acute kidney injury is common in critical illness and associated with important morbidity and mortality. Continuous renal replacement therapy (CRRT) enables physicians to safely and efficiently control associated metabolic and fluid balance disorders. The insertion of a large central venous catheter is required, which can be associated with mechanical and infectious complications. CRRT requires anticoagulation, which currently relies on heparin in most cases although citrate could become a standard in a near future. The choice of the substitution fluid depends on the clinical situation. A dose of 25 ml/kg/h is currently recommended.

Effect of age on intraoperative cerebrovascular autoregulation and near-infrared spectroscopy-derived cerebral oxygenation.

Background. Age is an important risk factor for perioperative cerebral complications such as stroke, postoperative cognitive dysfunction, and delirium. We explored the hypothesis that intraoperative cerebrovascular autoregulation is less efficient and brain tissue oxygenation lower in elderly patients, thus, increasing the vulnerability of elderly brains to systemic insults such as hypotension.Methods. We monitored intraoperative cerebral perfusion in 50 patients aged 18-40 and 77 patients >65 yr at two Swiss university hospitals. Mean arterial pressure (MAP) was measured continuously using a plethysmographic method. An index of cerebrovascular autoregulation (Mx) was calculated based on changes in transcranial Doppler flow velocity due to changes in MAP. Cerebral oxygenation was assessed by the tissue oxygenation index (TOI) using near-infrared spectroscopy. End-tidal CO(2), O(2), and sevoflurane concentrations and peripheral oxygen saturation were recorded continuously. Standardized anaesthesia was administered in all patients (thiopental, sevoflurane, fentanyl, atracurium).Results. Autoregulation was less efficient in patients aged >65 yr [by 0.10 (SE 0.04; P=0.020)] in a multivariable linear regression analysis. This difference was not attributable to differences in MAP, end-tidal CO2, or higher doses of sevoflurane. TOI was not significantly associated with age, sevoflurane dose, or Mx but increased with increasing flow velocity [by 0.09 (SE 0.04; P=0.028)] and increasing MAP [by 0.11 (SE 0.05; P=0.043)].Conclusions. Our results do not support the hypothesis that older patients' brains are more vulnerable to systemic insults. The difference of autoregulation between the two groups was small and most likely clinically insignificant.

Maternal effect on female caste determination in a social insect.

Caste differentiation and division of labor are the hallmarks of social insect colonies [1, 2]. The current dogma for female caste differentiation is that female eggs are totipotent, with morphological and physiological differences between queens and workers stemming from a developmental switch during the larval stage controlled by nutritional and other environmental factors (e.g., [3-8]). In this study, we tested whether maternal effects influence caste differentiation in Pogonomyrmex harvester ants. By conducting crossfostering experiments we identified two key factors in the process of caste determination. New queens were produced only from eggs laid by queens exposed to cold. Moreover, there was a strong age effect, with development into queens occurring only in eggs laid by queens that were at least two years old. Biochemical analyses further revealed that the level of ecdysteroids was significantly lower in eggs developing into queens than workers. By contrast, we found no significant effect of colony size or worker exposure to cold, suggesting that the trigger for caste differentiation may be independent of the quantity and quality of resources provided to larvae. Altogether these data demonstrate that the developmental fate of female brood is strongly influenced by maternal effects in ants of the genus Pogonomyrmex.

Hypoxie-ischémie cérébrale néonatale : rôle de la voie de JNK et implication de l'autophagie dans la mort neuronale

Résumé : Malgré les immenses progrès réalisés depuis plusieurs années en médecine obstétricale ainsi qu'en réanimation néonatale et en recherche expérimentale, l'asphyxie périnatale, une situation de manque d'oxygène autour du moment de la naissance, reste une cause majeure de mortalité et de morbidité neurologique à long terme chez l'enfant (retard mental, paralysie cérébrale, épilepsie, problèmes d'apprentissages) sans toutefois de traitement pharmacologique réel. La nécessité de développer de nouvelles stratégies thérapeutiques pour les complications de l'asphyxie périnatale est donc aujourd'hui encore essentielle. Le but général de ce travail est l'identification de nouvelles cibles thérapeutiques impliquées dans des mécanismes moléculaires pathologiques induits par l'hypoxie-ischémie (HI) dans le cerveau immature. Pour cela, le modèle d'asphyxie périnatale (proche du terme) le plus reconnu chez le rongeur a été développé (modèle de Rice et Vannucci). Il consiste en la ligature permanente d'une artère carotide commune (ischémie) chez le raton de 7 jours combinée à une période d'hypoxie à 8% d'oxygène. Il permet ainsi d'étudier les lésions de type hypoxique-ischémique dans différentes régions cérébrales dont le cortex, l'hippocampe, le striatum et le thalamus. La première partie de ce travail a abordé le rôle de deux voies de MAPK, JNK et p38, après HI néonatale chez le raton à l'aide de peptides inhibiteurs. Tout d'abord, nous avons démontré que D-JNKI1, un peptide inhibiteur de la voie de JNK présentant de fortes propriétés neuroprotectrices dans des modèles d'ischémie cérébrale adulte ainsi que chez le jeune raton, peut intervenir sur différentes voies de mort dont l'activation des calpaïnes (marqueur de la nécrose précoce), l'activation de la caspase-3 (marqueur de l'apoptose) et l'expression de LC3-II (marqueur de macroautophagie). Malgré ces effets positifs le traitement au D-JNKI1 ne modifie pas l'étendue de la lésion cérébrale. L'action limitée de D-JNKI1 peut s'expliquer par une implication modérée des JNKs (faiblement activées et principalement l'isotype JNK3) après HI néonatale sévère. Au contraire, l'inhibition de la voie de nNOS/p38 par le peptide DTAT-GESV permet une augmentation de 20% du volume du tissu sain à court et long terme. Le second projet a étudié les effets de l'HI néonatale sur l'autophagie neuronale. En effet, l'autophagie est un processus catabolique essentiel au bien-être de la cellule. Le type principal d'autophagie (« macroautophagie » , que nous appellerons par la suite « autophagie ») consiste en la séquestration d'éléments à dégrader (protéines ou organelles déficients) dans un compartiment spécialisé, l'autophagosome, qui fusionne avec un lysosome pour former un autolysosome où le contenu est dégradé par les hydrolases lysosomales. Depuis peu, l'excès ou la dérégulation de l'autoptiagie a pu être impliqué dans la mort cellulaire en certaines conditions de stress. Ce travail démontre que l'HI néonatale chez le raton active fortement le flux autophagique, c'est-à-dire augmente la formation des autophagosomes et des autolysosomes, dans les neurones en souffrance. De plus, la relation entre l'autophagie et l'apoptose varie selon la région cérébrale. En effet, alors que dans le cortex les neurones en voie de mort présentent des caractéristiques mixtes apoptotiques et autophagiques, ceux du CA3 sont essentiellement autophagiques et ceux du CA1 sont principalement apoptotiques. L'induction de l'autophagie après HI néonatale semble donc participer à la mort neuronale soit par l'enclenchement de l'apoptose soit comme mécanisme de mort en soi. Afin de comprendre la relation pouvant exister entre autophagie et apoptase un troisième projet a été réalisé sur des cultures primaires de neurones corticaux exposés à un stimulus apoptotique classique, la staurosporine (STS). Nous avons démontré que l'apoptose induite par la STS était précédée et accompagnée par une forte activation du flux autophagique neuronal. L'inhibition de l'autophagie de manière pharmacologique (3-MA) ou plus spécifiquement par ARNs d'interférence dirigés contre deux protéines autophagiques importantes (Atg7 et Atg5) a permis de mettre en évidence des rôles multiples de l'autophagie dans la mort neuronale. En effet, l'autophagie prend non seulement part à une voie de mort parallèle à l'apoptose pouvant être impliquée dans l'activation des calpaïnes, mais est également partiellement responsable de l'induction des voies apoptotiques (activation de la caspase-3 et translocation nucléaire d'AIF). En conclusion, ce travail a montré que l'inhibition de JNK par D-JNKI1 n'est pas un outil neuroprotecteur efficace pour diminuer la mort neuronale provoquée par l'asphyxie périnatalé sévère, et met en lumière deux autres voies thérapeutiques beaucoup plus prometteuses, l'inhibition de nNOS/p38 ou de l'autophagie. ABSTRACT : Despite enormous progress over the last«decades in obstetrical and neonatal medicine and experimental research, perinatal asphyxia, a situation of lack of oxygen around the time of the birth, remains a major cause of mortality and long term neurological morbidity in children (mental retardation, cerebral palsy, epilepsy, learning difficulties) without any effective treatment. It is therefore essential to develop new therapeutic strategies for the complications of perinatal asphyxia. The overall aim of this work was to identify new therapeutic targets involved in pathological molecular mechanisms induced by hypoxia-ischemia (HI) in the immature brain. For this purpose, the most relevant model of perinatal asphyxia (near term) in rodents has been developed (model of Rice and Vannucci). It consists in the permanent ligation of one common carotid artery (ischemia) in the 7-day-old rat combined with a period of hypoxia at 8% oxygen. This model allows the study of the hypoxic-ischemic lesion in different brain regions including the cortex, hippocampus, striatum and thalamus. The first part of this work addressed the role of two MAPK pathways (JNK and p38) after rat neonatal HI using inhibitory peptides. First, we demonstrated that D-JNKI1, a JNK peptide inhibitor presenting strong neuroprotective properties in models of cerebral ischemia in adult and young rats, could affect different cell death mechanisms including the activation of calpain (a marker of necrosis) and caspase-3 (a marker of apoptosis), and the expression of LC3-II (a marker of macroautophagy). Despite these positive effects, D-JNKI1 did not modify the extent of brain damage. The limited action of D-JNKI1 can be explained by the fact that JNKs were only moderately involved (weakly activated and principally the JNK3 isotype) after severe neonatal HI. In contrast, inhibition of nNOS/p38 by the peptide D-TAT-GESV increased the surviving tissue volume by around 20% at short and long term. The second project investigated the effects of neonatal HI on neuronal autophagy. Indeed, autophagy is a catabolic process essential to the well-being of the cell. The principal type of autophagy ("macroautophagy", that we shall henceforth call "autophagy") involves the sequestration of elements to be degraded (deficient proteins or organelles) in a specialized compartment, the autophagosome, which fuses with a lysosome to form an autolysosome where the content is degraded by lysosomal hydrolases. Recently, an excess or deregulation of autophagy has been implicated in cell death in some stress conditions. The present study demonstrated that rat neonatal HI highly enhanced autophagic flux, i.e. increased autophagosome and autolysosome formation, in stressed neurons. Moreover, the relationship between autophagy and apoptosis varies according to the brain region. Indeed, whereas dying neurons in the cortex exhibited mixed features of apoptosis and autophagy, those in CA3 were primarily autophagíc and those in CA1 were mainly apoptotic. The induction of autophagy after neonatal HI seems to participate in neuronal death either by triggering apoptosis or as a death mechanism per se. To understand the relationships that may exist between autophagy and apoptosis, a third project has been conducted using primary cortical neuronal cultures exposed to a classical apoptotic stimulus, staurosporine (STS). We demonstrated that STS-induced apoptosis was preceded and accompanied by a strong activation of neuronal autophagic flux. Inhibition of autophagy pharmacologically (3-MA) or more specifically by RNA interference directed against two important autophagic proteins (Atg7 and AtgS) showed multiple roles of autophagy in neuronal death. Indeed, autophagy was not only involved in a death pathway parallel to apoptosis possibly involved in the activation of calpains, but was also partially responsible for the induction of apoptotic pathways (caspase-3 activation and AIF nuclear translocation). In conclusion, this study showed that JNK inhibition by D-JNKI1 is not an effective neuroprotective tool for decreasing neuronal death following severe perinatal asphyxia, but highlighted two more promising therapeutic approaches, inhibition of the nNOSlp38 pathway or of autophagy.

Alda, l'esclave bretonne / par miss Strickland ; traduit de l'anglais par Mme Louise de Montanclos

Collection : Bibliothèque des écoles chrétiennes

Multiscale phylogeography: glacial history and autopolyploidy of Biscutella laevigata L. (Brassicaceae) in the Western Alps

Résumé Les changements climatiques du Quaternaire ont eu une influence majeure sur la distribution et l'évolution des biota septentrionaux. Les Alpes offrent un cadre spatio-temporel bien étudié pour comprendre la réactivité de la flore et le potentiel d'adaptation d'une espèce végétale face aux changements climatiques. Certaines hypothèses postulent une diversification des espèces en raison de la disparition complète de la flore des Alpes et d'un isolement important des espèces dans des refuges méridionaux durant les dernières glaciations (Tabula Rasa). Une autre hypothèse stipule le maintien de poches de résistance pour la végétation au coeur des Alpes (Nunataks). Comme de nombreuses espèces végétales présentant un grand succès écologique semblent avoir réagi aux glaciations par la multiplication de leur génome (autopolyploïdie), leur étude en milieu naturel devrait permettre de comprendre les avantages inhérents à la polyploïdie. Biscutella laevigata est un modèle emblématique de biogéographie historique, diverses études ayant montré que des populations diploïdes sont actuellement isolées dans les zones restées déglacées durant le dernier maximum glaciaire, alors que des tétraploïdes ont recolonisé l'ensemble des zones alpines mises à nu par le retrait des glaciers. Si le contexte périglaciaire semble avoir favorisé ce jeune complexe autopolyploïde, les circonstances et les avantages de cette mutation génomique ne sont pas encore clairs. Y a-t-il eu de multiples événements de polyploïdisation ? Dans quelle mesure affecte(nt)il(s) la diversité génétique et le potentiel évolutif des polyploïdes ? Les polyploïdes ont-ils une grande flexibilité génomique, favorisant une radiation adaptative, ou doivent-ils leur succès à une grande plasticité écologique ? Cette étude aborde ces questions à différentes échelles spatiales et temporelles. L'échelle régionale des Alpes occidentales permet d'aborder les facteurs distaux (aspects historiques), alors que l'échelle locale cherche à appréhender les facteurs proximaux (mécanismes évolutifs). Dans les Alpes occidentales, des populations ont été densément échantillonnées et étudiées grâce à (1) leur cytotype, (2) leur appartenance taxonomique, (3) leur habitat et (4) des marqueurs moléculaires de l'ADN chloroplastique, en vue d'établir leurs affinités évolutives. Á l'échelle locale, deux systèmes de population ont été étudiés : l'un où les populations persistent en périphérie de l'aire de distribution et l'autre au niveau du front actif de colonisation, en marge altitudinale. Les résultats à l'échelle des Alpes occidentales révèlent les sites d'intérêt (refuges glaciaires, principales barrières et voies de recolonisation) pour une espèce représentative des pelouses alpines, ainsi que pour la biodiversité régionale. Les Préalpes ont joué un rôle important dans le maintien de populations à proximité immédiate des Alpes centrales et dans l'évolution du taxon, voire de la végétation. Il est aussi démontré que l'époque glaciaire a favorisé l'autopolyploïdie polytopique et la recolonisation des Alpes occidentales par des lignées distinctes qui s'hybrident au centre des Alpes, influençant fortement leur diversité génétique et leur potentiel évolutif. L'analyse de populations locales en situations contrastées à l'aide de marqueurs AFLP montre qu'au sein d'une lignée présentant une grande expansion, la diversité génétique est façonnée par des forces évolutives différentes selon le contexte écologique et historique. Les populations persistant présentent une dispersion des gènes restreinte, engendrant une diversité génétique assez faible, mais semblent adaptées aux conditions locales de l'environnement. À l'inverse, les populations colonisant la marge altitudinale sont influencées par les effets de fondation conjugués à une importante dispersion des gènes et, si ces processus impliquent une grande diversité génétique, ils engendrent une répartition aléatoire des génotypes dans l'environnement. Les autopolyploïdes apparaissent ainsi comme capables de persister face aux changements climatiques grâce à certaines facultés d'adaptation locale et de grandes capacités à maintenir une importante diversité génétique lors de la recolonisation post-glaciaire. Summary The extreme climate changes of the Quaternary have had a major influence on species distribution and evolution. The European Alps offer a great framework to investigate flora reactivity and the adaptive potential of species under changing climate. Some hypotheses postulate diversification due to vegetation removal and important isolation in southern refugia (Tabula Rasa), while others explain phylogeographic patterns by the survival of species in favourable Nunataks within the Alps. Since numerous species have successfully reacted to past climate changes by genome multiplication (autopolyploidy), studies of such taxa in natural conditions is likely to explain the ecological success and the advantages of autopolyploidy. Early cytogeographical surveys of Biscutella laevigata have shed light on the links between autopolyploidy and glaciations by indicating that diploids are now spatially isolated in never-glaciated areas, while autotetraploids have recolonised the zones covered by glaciers- during the last glacial maximum. A periglacial context apparently favoured this young autopolyploid complex but the circumstances and the advantages of this genomic mutation remain unclear. What is the glacial history of the B. laevigata autopolyploid complex? Are there multiple events of polyploidisation? To what extent do they affect the genetic diversity and the evolutionary potential of polyploids? Is recolonisation associated with adaptive processes? How does long-term persistence affect genetic diversity? The present study addresses these questions at different spatiotemporal scales. A regional survey at the Western Alps-scale tackles distal factors (evolutionary history), while local-scale studies explore proximal factors (evolutionary mechanisms). In the Western Alps, populations have been densely sampled and studied from the (1) cytotypic, (2) morphotaxonomic, (3) habitat point of views, as well as (4) plastid DNA molecular markers, in order to infer their relationships and establish the maternal lineages phylogeography. At the local scale, populations persisting at the rear edge and populations recolonising the attitudinal margin at the leading edge have been studied by AFLPs to show how genetic diversity is shaped by different evolutionary forces across the species range. The results at the regional scale document the glacial history of a widespread species, representative of alpine meadows, in a regional area of main interest (glacial refugia, main barriers and recolonisation routes) and points out to sites of interest for regional biodiversity. The external Alps have played a major role in the maintenance of populations near the central Alps during the Last Glacial Maximum and influenced the evolution of the species, and of vegetation. Polytopic autopolyploidy in different biogeographic districts is also demonstrated. The species has had an important and rapid radiation because recolonisation took place from different refugia. The subsequent recolonisation of the Western Alps was achieved by independent lineages that are presently admixing in the central Alps. The role of the Pennic summit line is underlined as a great barrier that was permeable only through certain favourable high-altitude passes. The central Alps are thus viewed as an important crossroad where genomes with different evolutionary histories are meeting and admixing. The AFLP analysis and comparison of local populations growing in contrasted ecological and historical situations indicate that populations persisting in the external Alps present restricted gene dispersal and low genetic diversity but seem in equilibrium with their environment. On the contrary, populations colonising the attitudinal margin are mainly influenced by founder effects together with great gene dispersal and genotypes have a nearly random distribution, suggesting that recolonisation is not associated with adaptive processes. Autopolyploids that locally persist against climate changes thus seem to present adaptive ability, while those that actively recolonise the Alps are successful because of their great capacity to maintain a high genetic diversity against founder effects during recolonisation.

Predictability of drug expenditures: An application using morbidity data

The growth of pharmaceutical expenditure and its prediction is a major concern for policy makers and health care managers. This paper explores different predictive models to estimate future drug expenses, using demographic and morbidity individual information from an integrated healthcare delivery organization in Catalonia for years 2002 and 2003. The morbidity information consists of codified health encounters grouped through the Clinical Risk Groups (CRGs). We estimate pharmaceutical costs using several model specifications, and CRGs as risk adjusters, providing an alternative way of obtaining high predictive power comparable to other estimations of drug expenditures in the literature. These results have clear implications for the use of risk adjustment and CRGs in setting the premiums for pharmaceutical benefits.

Tolerance of whitefish embryos to Pseudomonas fluorescens linked to genetic and maternal effects, and reduced by previous exposure.

Juvenile or adult fish can alter their behaviour and rely on an innate and adaptive immune system to avoid/counteract pathogens, while fish embryos have to depend on egg characteristics and may be partly protected by their developing immune system that is building up from a certain age on. We developed an infection protocol that allows testing the reaction of individual whitefish embryos (Coregonus palaea) to repeated exposures to Pseudomonas fluorescens, an opportunistic bacterial fish pathogen. We used a full-factorial in vitro breeding design to separately test the effects of paternal and maternal contributions to the embryos' susceptibility to different kinds of pathogen exposure. We found that a first non-lethal exposure had immunosuppressive effects: pre-exposed embryos were more susceptible to future challenges with the same pathogen. At intermediate and high levels of pathogen intensity, maternal effects turned out to be crucial for the embryos' tolerance to infection. Paternal (i.e. genetic) effects played a significant role at the strongest level of infection, i.e. the embryos' own genetics already explained some of the variation in embryo susceptibility. Our findings suggest that whitefish embryos are largely protected by maternally transmitted substances, but build up some own innate immunocompetence several days before hatching.