Effects of early unilateral mandibular first molar extraction on condylar and ramal asymmetry / Efectos de la extracción temprana del primer molar mandibular unilateral sobre la asimetría condilar y ramal

SUMMARY: Craniofacial symmetry is an important factor in creating a harmonious facial appearance. Genetic and external factors may cause the formation of mandibular asymmetry. The aim of this study was to evaluate vertical mandibular asymmetries in adolescents who had unilateral mandibular first permanent molar (FPM) teeth extracted at an early age. The study group consisted of 60 subjects (30 females, 30 males with a mean age of 16.18±1.04 years) who had their mandibular permanent first molar tooth extracted before the age of 12, and the control group consisted of 60 healthy subjects (30 females, 30 males with a mean age of 16.23±0.92 years). Condylar asymmetry index (CAI), ramal asymmetry index (RAI), and condylar-ramal asymmetry index (CRAI) were calculated using panoramic radiographs of the subjects. Independent samples t-test was used to evaluate the differences between groups. CAI, RAI, and CRAI values were similar between male and female subjects in both control and study groups, and no statistically significant difference was found (p>0.05). No statistically significant difference was observed between the group who had their mandibular first permanent molar teeth extracted at an early age and the control group (p>0.05). CAI values were relatively higher in both groups, but there was no significant difference between the CAI, RAI, and CRAI values between the groups.

La simetría craneofacial es un factor importante para crear una apariencia facial armoniosa. Factores genéticos y externos pueden causar la formación de asimetría mandibular. El objetivo de este estudio fue evaluar las asimetrías mandibulares verticales en adolescentes a quienes se les extrajo el primer molar permanente (FPM) mandibular unilateral a una edad temprana. El grupo de estudio consistió en 60 sujetos (30 mujeres, 30 hombres con una edad media de 16,18±1,04 años) a quienes se les extrajo el primer molar mandibular permanente antes de los 12 años, y el grupo control consistió en 60 sujetos sanos (30 mujeres, 30 hombres con una edad media de 16,23±0,92 años). El índice de asimetría condilar (CAI), el índice de asimetría ramal (RAI) y el índice de asimetría condilar-ramal (CRAI) se calcularon utilizando radiografías panorámicas de los sujetos. Se utilizó la prueba t de muestras independientes para evaluar las diferencias entre los grupos. Los valores de CAI, RAI y CRAI fueron similares entre los hombres y las mujeres tanto en el grupo control como en el de estudio, y no se encontraron diferencias estadísticamente significativas (p>0.05). No se observaron diferencias estadísticamente significativas entre el grupo al que se le extrajo el primer molar permanente mandibular a una edad temprana y el grupo control (p>0,05). Los valores de CAI fueron relativamente más altos en ambos grupos, pero no hubo diferencias significativas entre los valores de CAI, RAI y CRAI entre los grupos.

A Systematic Review on Second Treatment-Free Remission (TFR) Attempt in Chronic Myeloid Leukemia (CML): Can it be Applied in Clinical Practice?

The prognosis and life expectancy of chronic myeloid leukemia (CML) patients have improved significantly with the launch of first tyrosine kinase inhibitor (TKI), imatinib. Maintaining at least one major molecular response in CML patients without the use of TKI is known as treatment-free remission (TFR). The safety of the first TFR (TFR1) effort has been reported by numerous studies. However, some patients relapse during TFR1. A second TFR (TFR2) can be tried again in those patients. This systematic review aims to evaluate individual patient characteristics for a TFR2, factors predicting successful TFR2, monitoring, consequences of the cessation of TKI, and studies about TFR2. We identified 5 studies related TFR2. The results showed that the first failed TKI discontinuation attempt is not an indicator of a second TKI discontinuation failure. TKIs could safely and successfully be discontinued for a second time in chronic phase CML patients despite a TFR1 failure. The most important factors for estimating TFR2 success are the speed of molecular relapse and the TKI-free duration after the first TKI discontinuation attempt. New trends in the management of CML patients are reducing the side effects of treatment, lessening the financial burden, and improving the quality of life of patients as CML has developed into a manageable chronic disease rather than an aggressive cancer. Although there are many studies and guidelines on TFR1, there are few studies on TFR2 and predictive factors. More data is still needed regarding TFR2 attempt in patients with CML.

Alterations in Facial Soft Tissue Thickness Post-Facemask Treatment in Noncleft Skeletal Class III and Bilateral Cleft Lip Palate Class III Patients.

OBJECTIVE: The purpose of this retrospective study was to assess the alteration in the facial soft tissue thickness after rapid maxillary expansion with facemask treatment in bilateral cleft lip and palate (BCLP) Class III patients and noncleft Class III patients. METHODS: Case records including lateral cephalograms of 30 patients (19 females, 11 males) treated using a rapid maxillary expansion with facemask treatment were analyzed. Group I (age: 11.4 ± 1.02 years) (10 females, 5 males) consisted of noncleft skeletal Class III patients, and group II (age: 10.8 ± 0.84 years) (9 females, 6 males) comprised skeletal Class III patients with bilateral cleft lip and palate. Fifteen hard tissue and 10 soft tissue measurements were made at the beginning and at the end of the treatment to evaluate the change with rapid maxillary expansion combined facemask treatment. RESULTS: The bilateral cleft lip and palate group displayed a statistically significant increase in the thickness of the subnasale, labrale superius, labrale inferius, labiomentale, and pogonion, whereas the thickness of the stomion was found to be significantly decreased. The noncleft group demonstrated a statistically significant decrease in the thickness of the stomion and gnathion. There was a statistically significant difference between the bilateral cleft lip and palate and noncleft groups in the facial soft tissue thickness measurements at labrale superius, gnathion, and subnasale points and in Y axis, U1-SN, U1-NA in the hard tissue measurements. CONCLUSION: The results of the study indicated that the rapid maxillary expansion with facemask treatment produced diverse alterations in the facial soft tissue thickness of bilateral cleft lip and palate patients and noncleft Class III patients.

A deep learning approach in automated detection of schizophrenia using scalogram images of EEG signals.

This study presents a method with high accuracy performance that aims to automatically detect schizophrenia (SZ) from electroencephalography (EEG) records. Unlike related literature studies using traditional machine learning algorithms, the features required for the training of the network are automatically extracted from the EEG records in our method. In order to obtain the time frequency features of the EEG signals, the signal was converted into 2D by using the Continuous Wavelet Transform method. This study has the highest accuracy performance in the relevant literature by using 2D time frequency features in automatic detection of SZ disease. It is trained with Visual Geometry Group-16 (VGG16), an advanced convolutional neural networks (CNN) deep learning network architecture, to extract key features found on scalogram images and train the network. The study shows a high success in classifying SZ patients and healthy individuals with a very satisfactory accuracy of 98% and 99.5%, respectively, using two different datasets consisting of individuals from different age groups. Using different techniques [Activization Maximization, Saliency Map, and Gradient-weighted Class Activation Mapping (Grad-CAM)] to visualize the learning outcomes of the CNN network, the relationship of frequency components between SZ and the healthy individual is clearly shown. Moreover, with these interpretable outcomes, the difference between SZ patients and healthy individuals can be distinguished very easily help for expert opinion.

Cephalometric evaluation of intrusion of maxillary posterior teeth by miniscrews in the treatment of open bite.

INTRODUCTION: The objective of this research was to investigate the effectiveness of orthodontic miniscrews for skeletal anchorage during anterior open bite treatment using cephalometric radiographs. METHODS: This study sample included 20 patients (mean age, 14.71; standard deviation, 1.77) with an anterior open bite. A total of 250 g of force was applied using elastic chains with anchorage from palatal miniscrew to an occlusal splint covering the posterior maxillary teeth. Cephalograms were obtained at the beginning of the treatment when the appliance was first applied and at the 8-month visit when treatment was completed. Paired t tests were used to identify statistically significant differences between initial and final measurements of skeletal and dental parameters. RESULTS: A decrease of 2.72 ± 1.90° in the SN-GoGn angle and 3.63 ± 1.87 mm in the anterior height (N-Me) parameter in the cephalometric evaluations indicated a significant improvement of vertically increased facial dimensions, with the intrusion of the maxillary posterior teeth (P <0.05). Anterior rotation of the mandible was determined by a 1.76 ± 1.09° increase in the SNB angle and a 1.86 ± 0.90° decrease in the ANB angle (P <0.05). Reductions in the open bite amount by 5.8 ± 0.90 mm, Mx6-SN by 4.00 ± 1.01 mm, and Mx6-PP by 4.01 ± 1.00 mm were indicative of significant intrusion in the maxillary posterior teeth (P <0.05). CONCLUSIONS: The present study confirmed that palatal miniscrew and maxillary occlusal splint caused intrusion of the maxillary posterior teeth, a decrease in the anterior open bite, and mandibular advancement, with anterior rotation after the maxillary posterior intrusion. We concluded that the treatment method in our study was appropriate for patients with Class I and mild Class II malocclusions and open bite anomalies.

Evaluation of Parents' Knowledge and Attitudes Towards Pediatric Dental Practice during the COVID-19 Pandemic.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic is a major public health crisis worldwide and it also has generated new challenges for dentistry. The aim of this study was to evaluate the knowledge and attitudes of the parents of pediatric patients about dental treatment during the COVID-19 pandemic through a questionnaire. MATERIALS AND METHODS: A structured questionnaire consisting of 15 multiple-choice questions and demographic information about the knowledge and attitudes of parents regarding dental treatment during the COVID-19 outbreak was used for the study. The participants were parents of pediatric patients (aged 8-14 years) who visited for a routine orthodontic examination at the department of orthodontics. RESULTS: A total of 250 participants responded to the questionnaire. The findings indicate that more than 95% of parents had information about the transmission paths of the virus, took COVID-19 seriously, and told their children about this disease. 34% of the parents thought that dental clinics were more dangerous than other social areas, and 39.2% thought their children could be infected by medical instruments during dental treatment. A statistically significant difference was observed between educational levels in the answers given about the transmission paths of the virus, the danger of dental clinics in terms of the virus, the permitted dental treatment procedures, and the personal protective equipment of the dentist (p < 0.05). CONCLUSION: Although most parents have information about COVID-19, there are differences in the knowledge and attitudes of parents during the pandemic period according to their educational level.

Effects of symmetric and asymmetric rapid maxillary expansion treatments on pharyngeal airway and sinus volume.

OBJECTIVE: To evaluate pharyngeal airway and maxillary sinus volumes following symmetric rapid maxillary expansion (RME) and asymmetric rapid maxillary expansion (ARME) treatment using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: The study consisted of 60 patients presenting to the orthodontics clinic with an indication that they required symmetric or asymmetric rapid maxillary expansion treatment. Individuals were included if they were aged 12-15 years and had symmetric (RME group; 14 girls, 16 boys) or asymmetric (ARME group; 16 girls, 14 boys) maxillary deficiency. Maxillary sinus volume (mm3) and pharyngeal airway volume (upper, lower, and total; mm3) were evaluated using CBCT records. The parameters were compared before treatment (T1) and after 3 months in retention (T2). RESULTS: All measurements at T2 were increased significantly compared with T1 in the RME group (P < .05). In the ARME group, changes in the lower pharyngeal airway and the nonaffected maxillary sinus volumes (non-affected side of maxillary sinus volumes) were not significant; however, the other measurements increased significantly from T1 to T2 (P < .05). Intergroup comparisons revealed that total pharyngeal airway volume and total maxillary sinus volume changes were significantly greater in the RME group. CONCLUSIONS: Pharyngeal airway and maxillary sinus volumes increased with both RME and ARME treatment. Both were found to be effective for treating transverse maxillary deficiency.

Is there a correlation between the aggressiveness of chronic asymptomatic prostatitis National Institutes of Health category IV and the Gleason score in patients with prostate cancer?

INTRODUCTION: We evaluated the correlation between the International Society of Urological Pathology (ISUP) grades and the aggressiveness grades of prostate inflammation in newly diagnosed prostate cancer patients with chronic asymptomatic prostatitis National Institiutes of Health (NIH) category IV (CAPNIHIV). METHODS: The study comprised 357 consecutive patients with prostate cancer in whom a cancer diagnosis had been made via a prostate needle biopsy. Histological sections of the prostate biopsy specimens of the patients were reviewed and scored. Prostatic inflammation was scored using the aggressiveness grade of inflammation. The associations between the ISUP grades and the aggressiveness grades of inflammation were analyzed using logistic regression. The limitations of the study were its retrospective design and the limited number of cases. RESULTS: In 110 (31%) patients, CAPNIHIV was detected: 56 (51%) patients had a grade 0 aggressiveness score, 34 (31%) patients had a grade 1 aggressiveness score, and 20 (18%) patients had a grade 2 aggressiveness score. The patients who had prostatic inflammation had 1.65 times (95% confidence interval [CI] 1.05-2.61) greater likelihood of a high ISUP grade (grade ≥3) compared with the patients who did not have prostatic inflammation. The association between the ISUP grade and the aggressiveness grade of inflammation was more pronounced for a grade 2 aggressiveness score (n= 20; odds ratio 2.97; 95% CI 1.14-7.71). CONCLUSIONS: In prostate cancer patients with CAPNIHIV, there was a positive correlation between the inflammation aggressiveness grade and the ISUP grade. The aggressiveness of intraprostatic inflammation may be an important morphological factor affecting the Gleason score.

Asymmetric dental arch treatment with Forsus fatigue appliances: Long-term results.

OBJECTIVES: To investigate the treatment efficacy and follow-up stability of the asymmetric Forsus appliance by evaluating longitudinal changes in dental arch asymmetry on digital dental models from 21 patients. MATERIALS AND METHODS: Maxillary and mandibular reference lines were used for measurements of intra-arch asymmetry at pretreatment (T1), posttreatment (T2), and 4.2 years after treatment (T3). Maxillary and mandibular measurements were performed relative to the dental midline and anterior reference line on digital dental models. To determine the amount of asymmetry between the Class I and Class II sides of a given arch, all maxillary and mandibular parameters were measured on each side of the model separately. Repeated-measures analysis of variance/paired sample t-tests were performed to evaluate dental arch asymmetries at the P < .05 level. RESULTS: The alveolar transverse dimensions of the posterior segment of both arches were increased during treatment (P < .05) and remained stable during the retention period. Class II subdivision malocclusion was caused by distal positioning of the mandibular canine, premolars, and first molar on the Class II side (P < .05). Asymmetry was resolved by treatment with asymmetric Forsus appliances. The resolved asymmetry remained stable over the long term. There were no significant differences between T2 and T3 (P > .05). CONCLUSIONS: The asymmetric Forsus appliance can be used to treat dental arch asymmetry in patients with Class II subdivision malocclusions.

Comparison of root resorption after bone-borne and tooth-borne rapid maxillary expansion evaluated with the use of microtomography.

INTRODUCTION: Root resorption was compared between bone-borne and tooth tissue-borne rapid maxillary expansion patients with the use of microtomography. METHODS: The study included 20 patients (ages 11-16 years) requiring fixed orthodontic treatment who underwent extraction of their first premolars after rapid maxillary expansion with the use of modified appliances. One side of the appliance covered the teeth with acrylic, while the other side was fixed to the palatal bone by means of a miniscrew. After 3 months' retention, the appliance was removed and teeth were extracted and examined with the use of microtomography. RESULTS: When the apical, middle, and cervical thirds, as well as the buccal and lingual sides, were compared, the volume loss was significantly higher in the tooth tissue-borne group than in the bone-borne group (P <0.01). The least volume loss occurred on the cervical third lingual surface in the tooth tissue-borne group and on the middle third buccal surface in the bone-borne group. In the former group, least resorption occurred on the cervical third and highest resorption on the buccal side. In the latter group, surfaces showed no significant changes. CONCLUSIONS: More root resorption occurred in the tooth tissue-borne group, mostly in the apical and middle thirds. The amount of resorption on the buccal surface was higher than that on the lingual surface.

Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: A large cohort real-life experience from Turkey (REACH-THEM).

OBJECTIVES: To evaluate the long-term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion-dependent thalassemia (TDT) and sickle cell anemia (SCA) in Turkey. METHODS: This was a multicenter, prospective cohort study including TDT and SCA patients aged 2-18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin [SF] level >1000 µg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice. RESULTS: A total of 439 patients were evaluated (415 [94.5%] TDT, 143 [32.6%] between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 µg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 µg/L), SCA (1655.5 to 1260 µg/L), and across age groups of 2-6 years (1971.5 to 1499 µg/L), 7-12 years (1688.5 to 1159.8 µg/L), and 13-18 years (1496.5 to 1107 µg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, -579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range. CONCLUSIONS: Deferasirox has long-term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.

Paricalcitol inhibits the Wnt/beta-catenin signaling pathway and ameliorates experimentally induced arthritis

Background/aim: The Wnt/ß-catenin pathway has important biological activities, including the differentiation of cells and joint formations. The aim of our study was to determine the effect of paricalcitol on experimentally induced arthritis. Materials and methods: Type II collagen combined with Freund's adjuvant was applied to induce arthritis in Wistar albino female rats. Paricalcitol (0.3 µg/kg daily) was subcutaneously injected starting 1 day after collagen applications (prophylactic group) or 1 day after the onset of arthritis (therapeutic group), until day 29. Results: The 29th day arthritis scores were lower compared to the 13th day scores in the paricalcitol groups (P < 0.05), while they were higher in the arthritis group (P < 0.05). Marked cartilage-bone destruction and extensive perisynovial inflammation were detected in the arthritis group. Decreased cartilage-bone destruction and perisynovial inflammation in the paws were observed in the paricalcitol groups. The tissue mRNA levels of DKK1, Wnt5a, and axin-2 were higher in the arthritis group than in the control group. In the paricalcitol groups, mRNA expressions were lower than in the arthritis group. Conclusion: The present study shows that the Wnt/ß-catenin signaling pathway is active in arthritis. Moreover, paricalcitol ameliorates arthritis via inhibiting the Wnt/ß-catenin pathway. Paricalcitol and the Wnt/ß-catenin pathway are candidates for research in human rheumatoid arthritis.

Pseudocholinesterase levels in patients under electroconvulsive therapy.

OBJECTIVES: In this study, we aimed to retrospectively assess the correlation of pseudocholinesterase (PChE) levels with age, gender, body weight and diagnosed psychiatric diseases in electroconvulsive therapy (ECT) cases. Methods: This retrospective study was conducted at Bülent Ecevit University Hospital, Zonguldak, Turkey, between 2007 and 2011. In the study, 193 ECT case files were retrospectively scanned to evaluate PChE values before ECT and other file information.  Results: There was no difference between gender in terms of PChE levels. Correlation analysis determined a weakly positive correlation between age (p=0.013; correlation coefficient [cc]: 0.178) and body weight (p less than 0.001; cc: 0.273) and PChE levels. No correlation was found between age, gender, weight or psychiatric diagnosis, and PChE levels.  Conclusion: Neuromuscular blockage is a significant factor that increases patient safety, while increasing the efficacy of ECT. In choosing muscle relaxant agents, both patient factors and the pharmacological properties of the neuromuscular blocker should be considered. We think that in situations with delayed recovery of ECT cases without identified PChE levels, low PChE levels must be considered.

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention.

OBJECTIVE: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. MATERIALS AND METHODS: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with ß-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). RESULTS: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all ß-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999. CONCLUSION: While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.

Retinal nerve fiber layer thickness in children with ß-thalassemia major.

PURPOSE: To measure the retinal nerve fiber layer thickness (RNFLT) in children with ß-thalassemia major and to compare with healthy controls. METHODS: A total of 47 patients with ß-thalassemia major and 51 healthy controls were included. Each subject underwent a standard ophthalmological examination. RNFLT measurements were performed using optical coherence tomography. RESULTS: Mean age of the patient group and healthy controls were 13.7 ± 2.1 and 14.3 ± 2.2 years, respectively. Mean peripapillary RNFL thickness was 94 µm in the patient group, and 100 µm in the control group (p < 0.01). In patients with ß-thalassemia major, RNFL was thinner in all quadrants than control subjects. Within the ß-thalassemia major group neither average RNFLT nor each four quadrant RNFLT were correlated with the age, serum ferritin or serum hemoglobin levels (p > 0.05). CONCLUSION: In this study, we observed RNFL was thinner in patients with ß-thalassemia major. Thinning of RNFL did not correlate with hemoglobin or ferritin levels.

Investigation of celiac disease followed by immune thrombocytopenic purpura diagnosis in patients and comparison with literature.

OBJECTIVE: Celiac disease (CD) and Immune thrombocytopenic purpura (ITP) may occur together as a result of similar autoimmune mechanisms. The aim of this study was to assess the frequency of CD in a group of ITP patients and in the literature. METHODS: A total of 29 patients in Pamukkale University Faculty of Medicine Hospital Pediatric Hematology and Oncology Department with ITP were included in the study. Test was performed for the antibodies related to CD. Positive result for celiac antibodies was confirmed with biopsy. The results were compared with the literature. RESULTS: Of the study group, 13 patients (44.8%) were female and 16 (55.2%) were male. The mean age was 7.2±4.7 years and mean platelet count at the time of admission was 13,440±11,110/mm3 (range: 2000-41,000/mm3). Twelve patients (41.4%) were diagnosed as acute ITP, 6 patients (20.7%) as persistent ITP, and 11 patients (37.9%) as chronic ITP, according to the duration of thrombocytopenia. Antibody positivity was detected in 1 patient. Histological evaluation was compatible with CD. Results were compared with studies regarding the prevalence of CD in the population. No significant difference was found. CONCLUSION: Although it is not necessary to perform CD test in every case of ITP, the presence of differential diagnosis of CD is important to prevent unnecessary treatment, especially in ITP patients with growth retardation or malabsorption findings.

A Rare Cause of Obstructive Sleep Apnea Syndrome: Retropharyngeal Lipoma.

Lipoma is the most common benign mesenchymal neoplasm. About 16% of lipomas arise in the head and neck region, especially in the posterior neck. Large lipomas that originate from the retropharyngeal space may cause dyspnea, dysphagia, and snoring and occasionally may lead to obstructive sleep apnea syndrome (OSAS). Herein, we report a 45-year-old male patient with OSAS caused by a giant retropharyngeal lipoma with emphasis on CT findings.