The impact of physical fitness on resilience to modern life stress and the mediating role of general self-efficacy.

Substantial evidence shows that physical activity and fitness play a protective role in the development of stress related disorders. However, the beneficial effects of fitness for resilience to modern life stress are not fully understood. Potentially protective effects may be attributed to enhanced resilience via underlying psychosocial mechanisms such as self-efficacy expectations. This study investigated whether physical activity and fitness contribute to prospectively measured resilience and examined the mediating effect of general self-efficacy. 431 initially healthy adults participated in fitness assessments as part of a longitudinal-prospective study, designed to identify mechanisms of resilience. Self-efficacy and habitual activity were assessed in parallel to cardiorespiratory and muscular fitness, which were determined by a submaximal step-test, hand strength and standing long jump test. Resilience was indexed by stressor reactivity: mental health problems in relation to reported life events and daily hassles, monitored quarterly for nine months. Hierarchical linear regression models and bootstrapped mediation analyses were applied. We could show that muscular and self-perceived fitness were positively associated with stress resilience. Extending this finding, the muscular fitness-resilience relationship was partly mediated by self-efficacy expectations. In this context, self-efficacy expectations may act as one underlying psychological mechanism, with complementary benefits for the promotion of mental health. While physical activity and cardiorespiratory fitness did not predict resilience prospectively, we found muscular and self-perceived fitness to be significant prognostic parameters for stress resilience. Although there is still more need to identify specific fitness parameters in light of stress resilience, our study underscores the general relevance of fitness for stress-related disorders prevention.

[Stopping antidepressants: withdrawal symptoms and rebound effects : Review and practical recommendations]. / Absetzen von Antidepressiva ­ Absetzsymptome und Rebound-Effekte : Übersicht und praktische Empfehlungen.

Stopping antidepressants can cause withdrawal (discontinuation) symptoms, the return of the original illness, and rebound. The latter means that the disease will return stronger, faster, or with greater likelihood than if it had not been treated with medication. The Psychiatry Working Group of the Drug Commission of the German Medical Association (AkdÄ) presents the scientific findings and provides practical recommendations for action. Withdrawal symptoms are multiform; unspecific physical symptoms are predominant. Distinguishing them from the recurrence of depressive symptoms can be difficult. Most of them are mild and self-limiting. There is insufficient evidence on the extent and frequency of rebound depression. The rebound risk implies that when establishing the medication, the short-term benefit must be weighed against the possible long-term risk of chronic depression or the possible need for long-term medication. Patients should be informed about the risk of withdrawal both as early as the joint decision-making process about treatment initiation and regularly during the course of treatment. Withdrawal should take place gradually, except in emergency situations, whereby small steps should be taken, especially in the low-dose range.

Longitudinal determination of resilience in humans to identify mechanisms of resilience to modern-life stressors: the longitudinal resilience assessment (LORA) study.

Resilience is the maintenance and/or quick recovery of mental health during and after periods of adversity. It is conceptualized to result from a dynamic process of successful adaptation to stressors. Up to now, a large number of resilience factors have been proposed, but the mechanisms underlying resilience are not yet understood. To shed light on the complex and time-varying processes of resilience that lead to a positive long-term outcome in the face of adversity, the Longitudinal Resilience Assessment (LORA) study has been established. In this study, 1191 healthy participants are followed up at 3- and 18-month intervals over a course of 4.5 years at two study centers in Germany. Baseline and 18-month visits entail multimodal phenotyping, including the assessment of mental health status, sociodemographic and lifestyle variables, resilience factors, life history, neuropsychological assessments (of proposed resilience mechanisms), and biomaterials (blood for genetic and epigenetic, stool for microbiome, and hair for cortisol analysis). At 3-monthly online assessments, subjects are monitored for subsequent exposure to stressors as well as mental health measures, which allows for a quantitative assessment of stressor-dependent changes in mental health as the main outcome. Descriptive analyses of mental health, number of stressors including major life events, daily hassles, perceived stress, and the ability to recover from stress are here presented for the baseline sample. The LORA study is unique in its design and will pave the way for a better understanding of resilience mechanisms in humans and for further development of interventions to successfully prevent stress-related disorder.

[Internet-based resilience training and prevention of mental disorders]. / Internetbasierte Resilienzförderung und Prävention psychischer Erkrankungen.

BACKGROUND: Resilience is associated with a positive and resource-oriented perspective. Therefore, it seems especially attractive for health promotion and prevention. In recent years, interventions to foster resilience have been increasingly developed, which train resilience factors and are mainly conducted in a face to face group format. OBJECTIVE: The question is raised what potential internet-based interventions (i-interventions) that train resilience factors have for health promotion and prevention. MATERIAL AND METHODS: Based on a narrative overview, the possibilities for i­interventions that train resilience factors for health promotion and prevention are investigated and the state of research is described. RESULTS: The effects of the i­interventions presented here, which aim at fostering resilience, on measures of mental health and well-being are heterogeneous and vary between low to high effects. Stronger evidence for the efficacy of these measures exists for more general i­interventions that also train resilience factors but are conceptualized for the prevention of specific disorders, such as depression or for stress reduction. DISCUSSION: Given the heterogeneous nature of intervention contents, theoretical foundations and therapeutic methods used, the heterogeneity of the evidence is discussed. In addition, perspectives for the further development of resource-oriented resilience interventions are outlined.

[Current concepts of resilience research]. / Aktuelle Konzepte der Resilienzforschung.

BACKGROUND: Stress-related mental disorders are the most prevalent and cost-intensive disorders of our time. On the other hand, the maintenance of mental health despite stressors, i. e. resilience, is a frequent phenomenon. Research on psychological resilience and its underlying mechanisms offers innovative possibilities for health promotion. It requires a consistent understanding of resilience and adequate methods of operationalization. OBJECTIVES: Modern concepts of the definition, operationalization and assessment of resilience as well as its implications for study designs in resilience research. MATERIAL AND METHODS: Analysis and discussion of current works and expert recommendations for the design of resilience research. RESULTS: Resilience research is undergoing a period of transition. Based on a new understanding of resilience as a dynamic and modifiable process, new approaches for operationalization and assessment were proposed. These include, for example, a transdiagnostic approach and the identification of resilience mechanisms, the consideration of stressor exposure in measuring the construct, and longitudinal cohort studies. CONCLUSIONS: In the upcoming decades, further profitable findings from current prospective longitudinal studies can be expected. One challenge for future resilience research consists in the continuous dissemination and implementation of the approaches described.

[Guideline-adherent inpatient psychiatric psychotherapeutic treatment of borderline personality disorder : Normative definition of personnel requirements]. / Leitliniengerechte stationäre psychiatrisch-psychotherapeutische Behandlung der Borderline-Persönlichkeitsstörung : Normative Personalbedarfsermittlung.

BACKGROUND: Borderline personality disorders (BPD) are severe mental diseases which place high pressure on the psychiatric healthcare system. Nowadays, well-tested, disorder-specific treatment concepts are available also for inpatient treatment in Germany. These show very good and long-term improvements in the psychopathology as well as posttreatment social participation; however, prerequisites for the implementation of these evidence-based inpatient psychotherapy programs are well-trained treatment teams and appropriate financing of resource expenditure. OBJECTIVE: The aim was to formulate a definition of normative needs for treatment duration and intensity for a guideline-conform, empirically proven and effective inpatient treatment of borderline personality disorder as well as the derived personnel requirements in comparison to the currently available resources within the framework of the Psychiatry Personnel Act (Psych-PV). MATERIAL AND METHODS: The resource requirements were established based on evaluated hospital ward models, the recommendations of the S2 guidelines and the criteria of specialist societies and compared with the personnel stipulations according to the Psych-PV. RESULTS: The results for a normatively established treatment program showed a pronounced deficit in the financing of the evaluated resource requirements, even when the stipulations laid down in the Psych-PV were implemented to 100 %. DISCUSSION: Disorder-specific inpatient treatment programs for borderline personality disorder have been scientifically proven to be highly effective; however, resource analyses show that the personnel requirements necessary for effective implementation of these programs are much higher than those allocated by the funding according to the Pysch-PV. The current underfunding leads to inadequate treatment outcomes with high readmission rates and as a result high direct and indirect costs of illness.

Creep cavitation can establish a dynamic granular fluid pump in ductile shear zones.

The feedback between fluid migration and rock deformation in mid-crustal shear zones is acknowledged as being critical for earthquake nucleation, the initiation of subduction zones and the formation of mineral deposits. The importance of this poorly understood feedback is further highlighted by evidence for shear-zone-controlled advective flow of fluids in the ductile lower crust and the recognition that deformation-induced grain-scale porosity is a key to large-scale geodynamics. Fluid migration in the middle crust cannot be explained in terms of classical concepts. The environment is considered too hot for a dynamic fracture-sustained permeability as in the upper crust, and fluid pathways are generally too deformed to be controlled by equilibrium wetting angles that apply to hotter, deeper environments. Here we present evidence that mechanical and chemical potentials control a syndeformational porosity generation in mid-crustal shear zones. High-resolution synchrotron X-ray tomography and scanning electron microscopy observations allow us to formulate a model for fluid migration in shear zones where a permeable porosity is dynamically created by viscous grain-boundary sliding, creep cavitation, dissolution and precipitation. We propose that syndeformational fluid migration in our 'granular fluid pump' model is a self-sustained process controlled by the explicit role of the rate of entropy production of the underlying irreversible mechanical and chemical microprocesses. The model explains fluid transfer through the middle crust, where strain localization in the creep regime is required for plate tectonics, the formation of giant ore deposits, mantle degassing and earthquake nucleation. Our findings provide a key component for the understanding of creep instabilities in the middle crust.

[Resource use and financing of guideline-adherent psychotherapeutic inpatient care]. / Aufwand und Finanzierung leitliniengerechter, psychotherapeutischer Behandlung im Krankenhaus.

BACKGROUND: The financing of psychiatric psychotherapeutic care in Germany is determined by the German psychiatric staffing regulations which are unchanged since 1991. Psychotherapy was established after 1991 as an effective and indispensable treatment of mental and behavioral disorders. AIMS AND OBJECTIVES: The aim of this study was to empirically investigate the use of psychiatrists' and psychologists' working time for psychotherapy in guideline-adherent hospital care. A further aim was to compare these results to the resources defined by the German psychiatric staffing regulations and in the new prospective payment system for psychiatry and psychosomatics in Germany. MATERIAL AND METHODS: University hospitals for psychiatry and psychotherapy were asked to retrospectively provide data of patients for which guideline-adherent care was possible. Participating institutions provided both data describing the staff time utilization of psychotherapeutic services provided by psychiatrists and psychologists and patient classifications according to the German psychiatric staffing regulations and the new prospective payment system for psychiatry and psychosomatics. RESULTS: Resources defined by the German psychiatric staffing regulations covered a mean of only 71 min of psychotherapy per patient and week while the actual mean intensity of psychotherapeutic care provided by the participating hospitals was 194 min per patient and week. The associated use of staff time was 102 min per patient and week. Both figures increased during an inpatient episode. The resources defined by the German psychiatric staffing regulations covered only 70 % of medical and psychological personnel. The current configuration of the new prospective payment system for psychiatry and psychosomatics covered only 59 % of staff time. CONCLUSION: The results of this study provide another unambiguous recommendation to adjust the out-dated German psychiatric staffing regulations to the current evidence and S3 guidelines for psychiatric psychotherapeutic hospital care. In particular, more resources are required for the provision of psychotherapeutic care.

Automated thresholding and analysis of microCT scanned bread dough.

Computer aided x-ray microtomography is an increasingly popular method to investigate the structure of materials. Continuing improvements in the technique are resulting in increasingly larger data sets. The analysis of these data sets generally involves executing a static workflow for multiple samples and is generally performed manually by researchers. Executing these processes requires a significant time investment. A workflow which is able to automate the activities of the user would be useful. In this work, we have developed an automated workflow for the analysis of microtomography scanned bread dough data sets averaging 5 GB in size. Comparing the automated workflow with the manual workflow indicates a significant amount of the time spent (33% in the case of bread dough) on user interactions in manual method. Both workflows return similar results for porosity and pore frequency distribution. Finally, by implementing an automated workflow, users save the time which would be required to manually execute the workflow. This time can be spent on more productive tasks.

Iatrogenic wandering spleen causing gastric outlet obstruction and perforation.

The phenomenon of a wandering spleen is rare with few published case reports. The cases published in the literature mainly result from acquired or congenital laxity of the spleen's anchoring ligaments. Our case demonstrates an uncommon complication and possibly the first reported case of an iatrogenic wandering spleen. We present an interesting case of a 51-year-old female patient with congenital adrenal hyperplasia, fibromyalgia, and rheumatoid arthritis who underwent robotic-assisted left adrenalectomy for a 10-cm adrenal mass. Postoperatively, she developed uncontrolled pain and gastric distension due to spleen entrapment, leading to an open laparotomy and splenectomy with gastric perforation repair. She made an uneventful recovery. The rarity of iatrogenic wandering spleen as well as our patient's complex medical history, including chronic steroid use, presented unique challenges in postoperative management. This case highlights the importance of thorough perioperative evaluation and careful surgical planning in patients with underlying conditions.

Disentangling common and specific neural subprocesses of response inhibition.

Response inhibition is disturbed in several disorders sharing impulse control deficits as a core symptom. Since response inhibition is a cognitively and neurally multifaceted function which has been shown to rely on differing neural subprocesses and neurotransmitter systems, further differentiation to define neurophysiological endophenotypes is essential. Response inhibition may involve at least three separable cognitive subcomponents, i.e. interference inhibition, action withholding, and action cancelation. Here, we introduce a novel paradigm - the Hybrid Response Inhibition task - to disentangle interference inhibition, action withholding and action cancelation and their neural subprocesses within one task setting during functional magnetic resonance imaging (fMRI). To validate the novel task, results were compared to a battery of separate, standard response inhibition tasks independently capturing these subcomponents and subprocesses. Across all subcomponents, mutual activation was present in the right inferior frontal cortex (rIFC), pre-supplementary motor area (pre-SMA) and parietal regions. Interference inhibition revealed stronger activation in pre-motor and parietal regions. Action cancelation resulted in stronger activation in fronto-striatal regions. Our results show that all subcomponents share a common neural network and thus all constitute different subprocesses of response inhibition. Subprocesses, however, differ to the degree of regional involvement: interference inhibition relies more pronouncedly on a fronto-parietal-pre-motor network suggesting its close relation to response selection processes. Action cancelation, in turn, is more strongly associated with the fronto-striatal pathway implicating it as a late subcomponent of response inhibition. The new paradigm reliably captures three putatively subsequent subprocesses of response inhibition and might be a promising tool to differentially assess disturbed neural networks in disorders showing impulse control deficits.

Prenatal adversity: a risk factor in borderline personality disorder?

BACKGROUND: Patients with borderline personality disorder (BPD) show a high prevalence of early adversity, such as childhood trauma. It has also been reported that prenatal adverse conditions, such as prenatal maternal stress, drug taking, tobacco smoking or medical complications, may be associated with an increased risk of mental disorders in the offspring. Prenatal adversity is investigated here for the first time as a potential risk factor in the diagnosis of BPD. Method A total of 100 patients with a DSM-IV diagnosis of BPD and 100 matched healthy controls underwent semi-structured interviews about the course of pregnancy, maternal stressors, birth complications and childhood trauma. Further information was obtained from the participants' mothers and from prenatal medical records. RESULTS: Borderline patients were significantly more often exposed to adverse intrauterine conditions, such as prenatal tobacco exposure (p=0.004), medical complications (p=0.008), prenatal maternal traumatic stress (p=0.015), familial conflicts (p=0.004), low social support (p=0.004) and partnership problems during pregnancy (p=0.014). Logistic regression analyses revealed that the reported prenatal risk factors accounted for 25.7% of the variance in BPD. Prenatal tobacco exposure [odds ratio (OR) 3.37, 95% confidence interval (CI) 1.49-7.65, p=0.004] and medical complications (OR 2.87, 95% CI 1.29-6.38, p=0.010) emerged as important predictors. After controlling for childhood adversity and parental socio-economic status (SES), prenatal risk factors predicted relevant borderline subdomains, such as impulsivity, affective instability, identity disturbance, dissociation and severity of borderline symptoms. CONCLUSIONS: This study provides evidence of an association between prenatal adversity and the diagnosis of BPD. Our findings suggest that prenatal adversity may constitute a potential risk factor in the pathogenesis of BPD.

[Antipsychotics for treatment of neuropsychiatric disorders in dementia]. / Antipsychotika zur Behandlung neuropsychiatrischer Störungen bei Demenz.

Antipsychotics, when used to treat neuropsychological symptoms associated with dementia, are associated with low effectiveness but a high risk of side effects. Some of these unwanted effects are severe and include an increased rate of cerebrovascular events and increased mortality. Although neuropsychiatric symptoms are frequently associated with dementia, it appears that antipsychotics are often used without clear indications and for too long time periods. Antipsychotics should be used only when all non-pharmacological strategies have failed. A clear definition of the treatment target in advance and a continuous monitoring of the therapy are mandatory.

Loneliness during the Covid-19 pandemic in Germany: Impact of social factors and polygenic risk scores on interpersonal differences in loneliness and mental health.

OBJECTIVES: The outbreak of Covid-19 negatively affected mental health and increased loneliness. The subjective feeling of loneliness is influenced by genetic and social factors and has a negative impact on mental health. METHODS: From March 2020 to June 2021 loneliness was investigated in N = 517 individuals using monthly acquired questionnaire data and Latent Growth Curve Analysis. Associations of social factors and polygenic risk scores (PRSs, n = 361) with class membership were investigated. RESULTS: Three classes ("average", 40%; "not lonely", 38%; "elevated loneliness", 22%) were identified, that differ significantly regarding loneliness, mental dysfunction, and response to the lockdown phases. Individuals with a high PRS for neuroticism are more likely to belong to the "elevated loneliness" class, living with another person is a protective factor. CONCLUSION: As the "elevated loneliness" class was at the highest risk of mental dysfunction, our findings underscore the importance of identifying those individuals to implement counteractive measures.

A meta-analysis of executive dysfunctions in unipolar major depressive disorder without psychotic symptoms and their changes during antidepressant treatment.

OBJECTIVE: Empirical evidence supports the existence of significant executive deficits in patients with major depressive disorder (MDD) as compared to non-depressed controls. Nevertheless, the effect size of executive dysfunctions in unipolar, non-psychotic MDD as well as their relationship to antidepressant treatment is ambiguous. METHOD: Meta-analytic methods were used to assess the severity of executive dysfunctions in unipolar, non-psychotic MDD as compared to healthy controls and to investigate their course during antidepressant treatment. RESULTS: Fifteen studies comparing the executive functions of 375 patients with DSM-IV MDD and 481 healthy controls were analysed. Furthermore, in three studies, including 122 patients with MDD, the Stroop test performance was examined before and after antidepressant treatment. Patients with MDD performed 0.439 up to 1.18 (P < 0.0001) standard mean differences worse than healthy controls. The Stroop performance improved during the course of treatment (P = 0.0001). CONCLUSION: We revealed significant executive dysfunctions in patients with unipolar, non-psychotic MDD compared with healthy controls and an improvement of the Stroop performance during the course of treatment. Future studies with different test procedures are needed to further investigate the influence of antidepressant treatment on executive functions.

The serotonin transporter promoter polymorphism (5-HTTLPR) affects the relation between antidepressant serum concentrations and effectiveness in major depression.

INTRODUCTION: Both the serotonin transporter promotor polymorphism (5-HTTLPR) and serum concentrations of SSRIs have been shown to affect response to SSRIs. Results, however, are inconsistent. The aim of this study was to investigate whether remission or response to SSRIs is influenced by an interaction of 5-HTTLPR and SSRI serum concentrations. METHODS: 49 patients with major depression and SSRI treatment were genotyped for the 5-HTTLPR locus including the rs25531. Drug serum concentrations and depression severity were measured weekly. RESULTS: Logistic regression analysis revealed a significant association between 5-HTTLPR, SSRI serum concentrations and response to treatment. A favourable treatment outcome correlated with SSRI serum concentration in 5-HTTLPR-L(A) allele carriers (r² = 34.3 %; p = 0.001), but not in S/L(G)-allele carriers (p = 0.31). DISCUSSION: In the group of L(A) allele carriers, those MDD patients with a high antidepressant serum concentrations responded better to treatment than patients with a low serum concentration. We conclude that the 5-HTTLPR might affect reponse to SRRI subject to serum concentrations. If replicated this might be a starting point for prospective clinical trials.

[Stimulant and non-stimulant medication in current and future therapy for ADHD]. / Psychostimulantien und Nicht-Stimulantien in der heutigen und zukünftigen ADHS-Therapie.

The current pharmacotherapy for attention-deficit hyperactivity disorder (ADHD) is mainly based on the stimulant methylphenidate and to a small extent on amphetamines which are not approved in Germany. The only approved non-stimulant so far is atomoxetin (Strattera®), a norepinephrine reuptake inhibitor. There is no approved pharmacotherapy for adults. The aim of the available medication is a reduction of impulsivity, hyperactivity, and attention deficits. Neurobiological correlates of these effects are still not fully understood, however, a functional implication of dopaminergic and noradrenergic systems is known. To date there is no disease-modifying therapy. The currently available substances have limitations due to the short half-life of stimulants, the unknown pathomechanisms, and the use of stimulants in developing brains with possible long-term side-effects. Moreover, the abuse potential of stimulants is still controversially discussed. The recently developed Lisdexamfetamin and SPD-465 have stimulant effects, too. A number of different developmental substances in preclinical and clinical phases show other mechanisms: SPD-503 represents an α(2)A-adrenozeptoragonist, ABT-089 and ABT-418 have partial agonistic effects to the α(4)ß(2)-subtype of nicotinic acetylcholinreceptors, CX-717, -1739, -1942 and -1796 are glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor agonists and PF-3 654 746 exhibits antagonistic properties to histaminergic H(3)-receptors. The α(2)A-adrenoceptor-agonist Guanfacine (Intuniv®) and the hepatic metabolised amphetamine prodrug Lisdexamfetamin (Vyvanse®) are yet approved for ADHD treatment in the USA. The aim of this review is to summarise established pharmacological treatment options and the stage of development of upcoming symptomatic stimulant and non-stimulant substances in ADHD therapy.

Epigenetic signatures in antidepressant treatment response: a methylome-wide association study in the EMC trial.

Although the currently available antidepressants are well established in the treatment of the major depressive disorder (MDD), there is strong variability in the response of individual patients. Reliable predictors to guide treatment decisions before or in an early stage of treatment are needed. DNA-methylation has been proven a useful biomarker in different clinical conditions, but its importance for mechanisms of antidepressant response has not yet been determined. 80 MDD patients were selected out of >500 participants from the Early Medication Change (EMC) cohort with available genetic material based on their antidepressant response after four weeks and stratified into clear responders and age- and sex-matched non-responders (N = 40, each). Early improvement after two weeks was analyzed as a secondary outcome. DNA-methylation was determined using the Illumina EPIC BeadChip. Epigenome-wide association studies were performed and differentially methylated regions (DMRs) identified using the comb-p algorithm. Enrichment was tested for hallmark gene-sets and in genome-wide association studies of depression and antidepressant response. No epigenome-wide significant differentially methylated positions were found for treatment response or early improvement. Twenty DMRs were associated with response; the strongest in an enhancer region in SORBS2, which has been related to cardiovascular diseases and type II diabetes. Another DMR was located in CYP2C18, a gene previously linked to antidepressant response. Results pointed towards differential methylation in genes associated with cardiac function, neuroticism, and depression. Linking differential methylation to antidepressant treatment response is an emerging topic and represents a step towards personalized medicine, potentially facilitating the prediction of patients' response before treatment.

Use of coffee, caffeinated drinks and caffeine tablets for cognitive enhancement in pupils and students in Germany.

INTRODUCTION: Substance use for cognitive enhancement (CE) is a topic of increasing importance. There are only few data about substances, prevalence rates and factors associated with CE. The aim of this study was to assess first data about the use of coffee, caffeinated drinks and caffeine tablets for CE at school and university. METHODS: A self-report questionnaire was developed to analyze 1 547 pupils and students about their use of coffee, caffeine tablets, and caffeinated drinks for CE and factors associated with this use. RESULTS: Lifetime, past-year, and past-month prevalence for the use of coffee for CE was 53.2%, 8.5%, and 6.3%, for the use of caffeinated drinks 39%, 10.7%, and 6.3%, and for the use of caffeine tablets 10.5%, 3.8%, and 0.8%. Use of caffeinated substances for CE was influenced by gender and school grades. DISCUSSION: The use of coffee and caffeinated drinks for CE was found to be widespread in the surveyed population. Although the use of caffeine tablets was found to be smaller than the above-mentioned means, it still indicates a relatively high disposition for using tablets for purposes of CE.