CBCovid19EC: A dataset complete blood count and PCR test for COVID-19 detection in Ecuadorian population.

In this work, we present the complete blood count data and PCR test results of a population of Ecuadorians from different provinces, primarily residing in the Andean region, especially in Quito. PCR was the standard test to detect Covid-19 during the pandemic since 2020. The data were obtained between March 1st and August 12th, 2021. Segurilab and Previne Salud laboratories performed the tests. The dataset contains about 400 clinical cases. Each patient agreed to participate in the study by sharing the results of their PCR (reverse transcription polymerase chain reaction) tests and CBC (complete blood count). CBC test measured several components and features of the blood, including red blood cells, white blood cells, hemoglobin, hematocrit, and platelets. The shared data are intended to provide researchers with input to analyze various events associated with the diagnosis of Covid-19 linked to potential diseases identified in the components measured in the CBC test. These data are helpful for pattern analysis of blood components in modeling prediction and clustering problems. The components measured in the complete blood count and CRP together can be helpful for the analysis of different medical conditions using machine learning algorithms.

Evaluation of a self-management patient education programme for fibromyalgia-results of a cluster-RCT in inpatient rehabilitation.

The objective was to evaluate the effectiveness of a self-management patient education programme for fibromyalgia syndrome (FMS) as compared with usual care education in inpatient rehabilitation. In a multicentre cluster-randomized controlled trial, 583 inpatients in 3 rehabilitation centres received an advanced self-management patient education programme or usual care education. Patients completed questionnaires at admission, discharge and after 6 and 12 months. Primary outcomes were disease- and treatment-specific knowledge at discharge, and self-management-competencies after 6 months. Secondary outcomes included satisfaction, attitudes, coping competencies, psychological distress and health impairment. We found a medium-sized effect on disease- and treatment-specific knowledge at discharge (P < 0.05, Cohen's d = 0.45, 95% CI = 0.27-0.63), and small effects for subjective knowledge, pain-related control, self-monitoring and insight, communication about disease, action planning for physical activity and treatment satisfaction (all P < 0.05). Only the effect on knowledge persisted for 6 and 12 months. This advanced education programme seemed to be more effective in the short term than usual education. However, intermediate- and long-term effects did not emerge. While superior long-term effects on knowledge as well as short-term effects on self-management skills may suggest implementation, additional long-term effects on other patient-relevant outcomes would be desirable. Trial registration: German Clinical Trials Register, DRKS00008782, Registered 8 July 2015.

Illness representations, pain and physical function in patients with rheumatic disorders: between- and within-person associations.

OBJECTIVES: Rehabilitation for patients with rheumatic diseases improves both illness representations (IR) and clinical outcomes such as pain and physical functioning (PF). However, it is unclear whether IR may affect and, in turn, are affected by pain and PF. In this study, we examined both between-person associations and within-person associations between IR and pain/PF over time on three measurement occasions. Furthermore, cross-lagged relationships were examined. DESIGN AND MAIN OUTCOME MEASURES: This secondary analysis is based on data from N = 186 patients with rheumatic diseases. Data on pain, PF and IR were assessed using self-report questionnaires at the beginning, the end and three months after a 3-week inpatient rehabilitation. METHODS: To separate between- and within-person level, data were analysed using random-intercept cross-lagged panel models. RESULTS: On both the between-person level (r = |0.21| - |0.44|) and the within-person level (r = |0.15| - |0.46|), pain and PF were related to cognitive and emotional IR. In addition, we found within-person bidirectional cross-lagged effects between emotional IR and PF. CONCLUSION: IR show complex relationships with pain and PF. Improving PF might improve subsequent illness-related emotional distress and vice versa.

Influence of different packing methods on the hydrodynamic stability of chromatography columns.

It is well known that packing non-uniformity may cause peak asymmetry and limit the performance of packed-bed chromatographic columns. However, understanding of the reasons leading to packing non-uniformity is still limited. Therefore, the effect of different column packing methods, i.e. dynamic axial compression (DAC), flow packing, and combinations of both on the hydrodynamic packing heterogeneity and stability of packings composed of polymer-based compressible porous resins with a mean diameter of 90µm was investigated experimentally as well as in-silico. Deterministic Euler-Lagrange modeling of a small chromatographic column with a diameter of 9.6mm and a bed height of 30mm was applied by coupling Computational Fluid Dynamics (CFD) and the Discrete Element Method (DEM). Interparticle micromechanics as well as the fluid-particle and particle-wall interactions were taken into account. Experiments and simulations revealed substantial non-uniformity of compression force transmission and axial packing density distribution during both dynamic axial compression and flow packing which was related to wall support and interparticle friction. By combining both packing methods sequentially (dynamic axial compression followed by flow packing or vice versa), the compression forces were more homogeneous resulting in improved packing procedures. Repeated alternating application of flow packing and DAC (the so-called hybrid packing method) resulted in the most homogeneous packing density distribution and the highest packing stability which was kept nearly constant during long-term operation with cyclic hydrodynamic load. The hydrodynamic stability of the chromatographic column was evaluated by calculating the integral porosity deviation and packing induced flow velocity dispersion. The hybrid packing method gave the best results for both parameters.

[Evaluation of effectiveness of education in rheumatology : Recommendations according to a patient education model]. / Wirksamkeitsprüfung rheumatologischer Schulungen : Empfehlungen nach einem Wirkmodell der Patientenschulung.

Patient education in rheumatology should be evidence-based. As recommended by the European League Against Rheumatism (EULAR) the outcomes of evaluation studies should be based on the goals of the education program. In Germany the goals of education programs have been described for all relevant rheumatological indications, various education programs have been published and evaluated. Our model of patient education outcomes distinguishes proximal and distal outcomes that should be used in effectiveness studies. Proximal goals include health literacy (e.g. knowledge, skills, attitudes and motivation) and empowerment. These can be directly influenced by the educational elements of a program. Distal outcomes include self-management behavior (e.g. health behavior, adherence, coping and emotion regulation), morbidity, functioning, quality of life and participation. The latter can be influenced by proximal outcomes and moderated by a number of personal and environmental factors. The results of a literature search summarize appropriate measurements for these outcomes. For distal outcomes, valid instruments exist in the German language for some rheumatological indications. To assess proximal goals there are still developmental needs. We recommend choosing proximal and distal outcomes for evaluation according to the model of patient education outcomes and to test the relationships between these outcomes.

[Work-related medical rehabilitation for patients with rheumatic diseases]. / Medizinisch-berufliche Orientierung in der Rehabilitation von Rheumakranken.

In recent years work-related rehabilitation has been intensified. Several studies have shown the effectiveness of work-related interventions in medical rehabilitation by improving participation in the work force and reducing sick leave. The German pension insurance fund has developed standardized requirements for medical work-related rehabilitation which include diagnostic procedures to identify patients with specific occupational problems and vocation-related interventions. These requirements address patients across different indications and diagnoses. Rehabilitation centers are assigned to different levels of work-related interventions depending on the intensity and specificity of the profile. Centers providing the complete range of work-related interventions offer differentiated work-related diagnostics, job training and occupational groups in addition to general social advice. In this article four case studies with different priorities regarding vocational interventions are presented.

Influence of graphene exfoliation on the properties of water-containing adlayers visualized by graphenes and scanning force microscopy.

Molecular adlayers on mica have been visualized previously by coating the sample with graphene and imaging it by scanning force microscopy. While it had been argued that this shows that ambient water on mica exhibits ice-like structures, recent apparently similar experiments indicate different behaviors. Here, we demonstrate that adhesive tapes, which are often used to mechanically exfoliate graphenes onto solid substrates, can lead to water-containing adlayers, which differ substantially from pure water layers. We exfoliated graphenes with the aid of different adhesive tapes and demonstrate that the results depend on the particular tape. Our results imply that structure and properties of confined water adlayers can be controlled by minor amounts of additives.

["Vocational perspective"--short-term efficacy of a group treatment for patients with extensive work-related problems during medical rehabilitation]. / "Berufliche Zukunft"--Kurzzeiteffekte eines Behandlungsprogramms bei sozialmedizinisch relevanter Problemlage im Verlauf einer medizinischen Rehabilitation.

AIM OF THE STUDY: To analyze the short-term efficacy of the Vocational Perspective programme for patients identified as having extensive work-related problems during rheumatology or orthopaedic inpatient rehabilitation. The primary objectives of the programme on patient level are to convey information about the legal provisions regarding earning incapacity and occupational reintegration, to suggest strategies for dealing with one's own occupational situation, and to strengthen the motivation to stay employed. The programme is explicitly designed for patients who wish to retire or have applied for a pension. On the systemic level, the main goals are to facilitate doctor-patient communication and to increase rehabilitation teams' awareness of occupational problems. METHODS: In a controlled quasi-experimental design, 359 subjects were consecutively assigned to either the control group (CG, n=177) or the intervention group (IG, n=182). The control group received standard care only, whereas the intervention group additionally participated in the 5-part Vocational Perspective programme. Evaluation criteria were assessed by questionnaire at the beginning (t1) and at end of rehabilitation (t2). Survey participation was 92.2% at t2. The socio-medically relevant knowledge status was objectively documented using a specially designed knowledge questionnaire. Aspects of treatment satisfaction were evaluated using individual items, and the subjective prognosis of gainful employment was assessed using the Subjective Prognosis of Gainful Employment (SPE) scale. Facilitation of communication between doctor and patient was operationalized at patient level in terms of patient satisfaction with medical care, and increased awareness of the rehabilitation team was operationalized in terms of the rate of recommendations to apply for vocational reintegration (LTA) services at discharge. Emotional and functional parameters were exploratively analyzed (anxiety and depression using the IRES 3.1 scales, and subjectively experienced pain-related impairment using the Pain Disability Index). RESULTS: Scores for subjective satisfaction with job-related information, medical care, socio-medical assessment, and the overall benefits of rehabilitation were significantly higher in the intervention group than in the control group. IG subjects moreover were better able to use the rehabilitation measure to clarify their occupational situation and exhibited significantly greater improvement of socio-medically relevant knowledge. Age proved to be an important predictor of change in a patient's subjective prognosis for gainful employment (SPE): A positive change in SPE was observed in both groups in subjects under 50, in those aged 50 and older, however, only in the intervention group. No differences between the two groups were observed in terms of functional and emotional parameters (e. g., disability through pain, anxiety, and depression). A total of 60% of the subjects received a recommendation at discharge to apply for vocational reintegration services, the proportion however was significantly higher in the IG. CONCLUSIONS: The Vocational Perspective programme met the patients' high demand for information on relevant socio-medical facilities and services regarding career change and facilitated communication between the doctor and patient by creating greater transparency. The improvement of subjective prognosis for gainful employment observed in the subgroup of older patients indicates that specialized interventions are needed in precisely this disadvantaged group in order to improve their own vocational expectations and thus to improve their chances of reintegration into work life. The high rate of recommendations to apply for vocational reintegration services suggests that rehabilitation teams already have a high awareness of job-related problems even under "usual care" conditions.

Replication of single macromolecules with graphene.

The electronic properties of graphenes depend sensitively on their deformation, and therefore strain engineered graphene electronics is envisioned. In order to deform graphenes locally, we have mechanically exfoliated single and few layer graphenes onto atomically flat mica surfaces covered with isolated double stranded plasmid DNA rings. Using scanning force microscopy in both contact and intermittent contact modes, we find that the graphenes replicate the topography of the underlying DNA with high precision. The availability of macromolecules of different topologies, e.g., programmable DNA patterns, render this approach promising for new graphene based device designs. On the other hand, the encapsulation of single macromolecules offers new prospects for analytical scanning probe microscopy techniques.

["Vocational perspective" - concept and acceptance of a group treatment for patients with extensive work-related problems]. / "Berufliche Zukunft" - Konzept und Akzeptanz eines Behandlungsprogramms bei sozialmedizinisch relevanter beruflicher Problemlage.

BACKGROUND: The treatment programme "Vocational Perspective" was developed for patients with health-related social problems, e. g. long-term sick leave, job loss due to disability, job insecurity and psychosocial disabilities. It intends the patient-oriented imparting of information referring to social system, legal rights, earning capacity and occupational reintegration as well as an early feedback of the sociomedical assessment by the physicians. Participants during in-patient rehabilitation are supported to deal with their occupational situation; motivation to stay employed is strengthened. The group programme contains five psychoeducative modules and an additional sociomedical "ward round". The aim of the study was to examine the acceptance of the newly developed sociomedical vocational therapy module. METHOD: A total of 179 patients participated in 21 "vocational perspective" seminars within the scope of a controlled quasi-experimental trial. In the experimental group the data on acceptance of the treatment was assessed by questionnaire at the end of the intervention. Experiences with implementation of the programme are described in order to complete the patient-related perspective. RESULTS: The identification of a demand for work-related interventions in medical rehabilitation seemed successful: Sociodemographic and socioeconomical parameters of the sample proved high risk in view of the social-medical perspective (poor education, high unemployment rates and long-term sick leave). Self-estimations revealed high suffering of the participants, e. g. due to the occupational situation, anxiety and depression, and confirmed high interest in work-related issues. The patients showed quite high acceptance of the programme (regarding importance of seminar, comprehensibility, usefulness of information, atmosphere of the group, mode and extent of the programme). 82.7% of the participants would recommend the programme to other people with work-related problems. Altogether, the experiences during the implementation of the programme can be described as positive. Nevertheless, organizing took much effort and the treatment was very demanding for the therapists. Finally, it is also necessary that the physicians agree to realize high transparency in the process of sociomedical assessment. CONCLUSION: The sociomedical programme "Vocational Perspective" helps patients to deal with relevant information referring to social system and occupational reintegration. Problematical sociomedical issues can be handled in a therapeutic way during rehabilitation process. Therefore, the programme can be used as meaningful supplement in regular medical rehabilitation. For final conclusions, the results of short-term and follow-up evaluations described elsewhere have to be considered.

High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.

Maternal low-protein diet during pregnancy is a risk factor for cardiovascular disease of the offspring in later life. The impact of high-protein diet during pregnancy on the cardiovascular phenotype of the offspring, however, is still unknown. We examined the influence of a high-protein diet during pregnancy and lactation on the renal, hemodynamic, and metabolic phenotype of the F1 generation. Female Wistar rats were either fed a normal protein diet (20% protein: NP) or an isocaloric high-protein diet (40% protein: HP) throughout pregnancy and lactation. At weaning, the offspring were fed with standard diet, and they were allocated according to sex and maternal diet to four groups: normal-protein male (NPm, n = 25), normal-protein female (NPf, n = 19), high-protein male (HPm, n = 24), high-protein female (HPf, n = 29). During the experiment (22 wk), the animals were characterized by repeated measurement of body weight, food intake, blood pressure, glucose tolerance, energy expenditure, and kidney function. At the end of the study period histomorphological analyses of the kidneys and weight measurement of reproductive fat pads were conducted. There were no differences in birth weight between the study groups. No influence of maternal diet on energy expenditure, glucose tolerance, and plasma lipid levels was detected. Blood pressure and glomerulosclerosis were elevated in male offspring only, whereas female offspring were characterized by an increased food efficiency, higher body weight, and increased fat pads. Our study demonstrates that a high-protein diet during pregnancy and lactation in rats programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner.

[Long term change in quality of life after adenotonsillectomy for pediatric obstructive sleep disorders]. / Anderung der Lebensqualität nach Adenotonsillektomie bei Kindern mit obstruktiven schlafbezogenen Atmungsstörungen.

BACKGROUND: To study short-term and long-term changes in quality of life (QOL) in children before and after adenotonsillectomy (T and A) for obstructive sleep disorders (OSDs). MATERIALS AND METHODS: Prospective study of 20 children underwent T and A for OSDs at the University hospital of Ulm/Germany. Caregivers were asked to complete the Brouillette-Score (BS) and OSA-18 survey, validated instruments for detecting symptoms and QOL change in children with OSDs, at the initial office visit prior to surgery (BS/1 and OSA-18/1) within 7.5 +/- 1.14 weeks after surgery (BS/2 and OSA-18/2), and 14.8 +/- 1.98 months after surgery (BS/3 and OSA-18/3). The BS comprises 3 items including: difficulty breathing during sleep, apnea observed by the caregivers and snoring. The OSA-18 survey comprises 18 items in 5 domains of sleep disturbance, physical suffering, emotional distress, daytime problems, and caregiver concerns. Scores from the preoperative and postoperative surveys were compared using the paired T-test and SPEARMAN-RANK test. RESULTS: 13 children were male (65 %). The mean age at the time of inclusion in the study was 6.2 +/- 1.63 years, mean preoperative body mass index (BMI) was 17.4 +/- 1.24 kg/m(2). Brouillette-Score: The mean Brouillette-Score before T and A (2.72) was significantly higher ( P = or < .001) than in the short-term (- 2.19) and in the long-term. (- 3.54). OSA-18 SURVEY: The mean total score for OSA-18/1 (83.4) was significantly higher ( P = or < .001) than the mean total score for OSA-18/2 (29.8) and OSA-18/3 (25.6). The overall correlation between BS and OSA-18 was R = .887 ( P = or < .001). CONCLUSION: Children with suspicious OSDs demonstrate significant short term and long-term improvement in the Brouillette-Score and OSA-18 survey. Caregivers perceive a long-term improvement for a minimum of one year in QOL after T and A for OSDs, although these improvements are not uniform across all domains of the OSA-18 survey. Use of the Brouillette-Score and the OSA-18 survey should decrease the need for polysomnographic monitoring and facilitate selection of children for T and A, whereas the OSA-18 questionnaire permits the more differentiated finding.

Depth profile of uncompensated spins in an exchange bias system.

We have used the unique spatial sensitivity of polarized neutron and soft x-ray beams in reflection geometry to measure the depth dependence of magnetization across the interface between a ferromagnet and an antiferromagnet. The net uncompensated magnetization near the interface responds to applied field, while uncompensated spins in the antiferromagnet bulk are pinned, thus providing a means to establish exchange bias.

[Controlled clinical testing of an antidiarrheal]. / Kontrollierte klinische Prüfung eines Antidiarrhoikums.

AIM: To identify the efficacy and tolerance of activated charcoal in acute, nonspecific diarrhea. METHOD: Randomized, double-blind study on 100 adults with nonspecific diarrhea, performed in two general practices. 94 were included in the final analysis, 6 patients - all from the placebo group abandoned treatment because of the absence of an effect. RESULTS: The major outcome parameters - reduction of stool frequency and curtailment of the duration of the diarrhea - were unequivocally achieved. Differences between the agent and placebo were great. Stool frequency decreased significantly from the third day in the drug group, and highly significantly from the fourth day. The superiority of the antidiarrheal was also clearly evident in terms of the numbers of days with diarrhea, the clinical findings tympania, nature of the stool and of eight individual symptoms, the summed score of which was improved highly significantly by the test substance. CONCLUSION: The substance tested proved rapidly and reliably effective in the treatment of nonspecific diarrhea, and was well tolerated. Activated charcoal, together with oral rehydration, can therefore be recommended as an initial measure for treating diarrhea with the aim of rapidly and effectively preventing loss of fluid and electrolytes and relieving symptoms.

[Tolerance and effectiveness of oxymetazoline and xylometazoline in treatment of acute rhinitis]. / Verträglichkeit und Wirksamkeit von Oxymetazolin* und Xylometazolin bei der Behandlung der akuten Rhinitis.

BACKGROUND: Local alpha-sympathomimetics in hydrous solution are well known in the therapy of acute rhinitis and sinusitis. However, added preservatives like benzalkonium chloride have a negative effect on compatibility. PATIENTS AND METHOD: A total of 307 patients with acute rhinitis entered the study. The treatment with oxymetazoline with preservative, oxymetazoline without preservative and xylometazoline with preservative was evaluated. RESULTS: This randomised, double-blind, multi-centered, verum-controlled tolerance study confirmed that the local sympathomimetics oxymetazoline and xylometazoline are well tolerated in the treatment of acute rhinitis. When evaluated according to the parameters "feeling of dryness in nasal mucosa" and "burning sensation", the Nasivin sanft 0.05% spray, which contains the active agent oxymetazoline without preservatives, proved to be considerably superior to preparations containing the preservative benzalkonium chloride. CONCLUSION: Preparations without preservatives should be the preferred choice of treatment for acute rhinitis.

[Postoperative management following rhinosurgery interventions in severe obstructive sleep apnea. A pilot study]. / Postoperatives Management nach rhinochirurgischen Eingriffen bei schwerer obstruktiver Schlafapnoe. Eine Pilotstudie.

BACKGROUND: Patients with severe obstructive sleep apnea (OSA) treated by nasal continuous positive airway pressure (CPAP) often undergo rhinosurgery to improve nasal ventilation and comply with CPAP therapy. The use of nasal packing postoperatively may worsen the severity of their sleep-related breathing disorders, even leading to death. For this reason, postoperative surveillance with CPAP ventilation is recommended. An oral connection piece offers the possibility to continue CPAP therapy. PATIENTS AND METHOD: Five patients with OSA were enrolled in this pilot study. All patients underwent a septorhinoplasty with nasal packing for 2 days. CPAP ventilation was guaranteed postoperatively by using an oral connection piece. The object of the study was to evaluate the feasibility, effectiveness, and acceptance of CPAP ventilation with this oral connection piece in patients with nasal packing. Therefore, the blood oxygenation of the patients was observed by pulse oximetry pre- and postoperatively. RESULTS: None of the patients with nasal packing showed apneas or hypopneas with arterial blood oxygen saturation below 92%. Application of oxygen was not necessary. Cardiorespiratory or neurological complications were not observed. CONCLUSION: The oral connection piece offers a feasible and effective opportunity to continue CPAP ventilation therapy after rhinosurgery in patients with OSA. The acceptance of the method is satisfactory.

Identification and characterization of a family of Rab11-interacting proteins.

Rab11a is a small GTP-binding protein enriched in the pericentriolar plasma membrane recycling systems. We hypothesized that Rab11a-binding proteins exist as downstream effectors of its action. Here we define a family of four Rab11-interacting proteins: Rab11-Family Interacting Protein 1 (Rab11-FIP1), Rab11-Family Interacting Protein 2 (Rab11-FIP2), Rab11-Family Interacting Protein 3 (Rab11-FIP3), and pp75/Rip11. All four interacting proteins associated with wild type Rab11a and dominant active Rab11a (Rab11aS20V) as well as Rab11b and Rab25. Rab11-FIP2 also interacted with dominant negative Rab11a (Rab11aS25N) and the tail of myosin Vb. The binding of Rab11-FIP1, Rab11-FIP2, and Rab11-FIP3 to Rab11a was dependent upon a conserved carboxyl-terminal amphipathic alpha-helix. Rab11-FIP1, Rab11-FIP2, and pp75/Rip11 colocalized with Rab11a in plasma membrane recycling systems in both non-polarized HeLa cells and polarized Madin-Darby canine kidney cells. GFP-Rab11-FIP3 also colocalized with Rab11a in HeLa cells. Rab11-FIP1, Rab11-FIP2, and pp75/Rip11 also coenriched with Rab11a and H(+)K(+)-ATPase on parietal cell tubulovesicles, and Rab11-FIP1 and Rab11-FIP2 translocated with Rab11a and the H(+)K(+)-ATPase upon stimulating parietal cells with histamine. The results suggest that the function of Rab11a in plasma membrane recycling systems is dependent upon a compendium of protein effectors.

Survey on the usefulness of trazodone in patients with PTSD with insomnia or nightmares.

BACKGROUND: Trazodone is commonly used in the treatment of insonmia and nightmares in patients with PTSD. There is little evidence in the literature for this practice. METHOD: Seventy-four patients from the Palo Alto Veterans Affairs Health Care System in California who were admitted to a specialized 8 week inpatient treatment program for PTSD were surveyed regarding their use of trazodone in the treatment of insomnia or nightmares. Patients were asked to complete a questionnaire regarding trazodone's effectiveness, side effects, and optimal doses. RESULTS: Of 74 patients surveyed, 60 patients were able to maintain an effective dose of trazodone. The other 14 patients were unable to tolerate the medication. Seventy-two percent of the 60 patients assessed found trazodone helpful in decreasing nightmares, from an average of 3.3 to 1.3 nights per week (p<.005). Ninety-two percent found it helped with sleep onset, and 78% reported improvement with sleep maintenance. There was a significant correlation between the effectiveness in decreasing nightmares and improving sleep (r= .57, p < .005). The effective dose range of trazodone for 70% of patients was 50 to 200 mg nightly. Of the 74 patients surveyed, 9 (12%) reported priapism. CONCLUSION: Trazodone appears effective for the treatment of insomnia and nightmares associated with chronic PTSD. However, controlled trials are needed before any definite conclusions can be drawn. The higher than expected occurrence of priapism warrants clinicians asking directly about this side effect.