Tissue S100/calgranulin expression and blood neutrophil-to-lymphocyte ratio (NLR) in dogs with lower urinary tract urothelial carcinoma.

BACKGROUND: Urothelial carcinoma (UC) is the most common neoplasm of the canine lower urinary tract, affecting approximately 2% of dogs. Elderly female patients of certain breeds are predisposed, and clinical signs of UC can easily be confused with urinary tract infection or urolithiasis. Diagnosis and treatment are challenging given the lack of disease-specific markers and treatments. The S100A8/A9 complex and S100A12 protein are Ca2+-binding proteins expressed by cells of the innate immune system and have shown promise as urinary screening markers for UC. The neutrophil-to-lymphocyte ratio (NLR) can also aid in distinguishing certain neoplastic from inflammatory conditions. Our study aimed to evaluate the tissue expression of S100/calgranulins and the blood NLR in dogs with UC. Urinary bladder and/or urethral tissue samples from dogs with UC (n = 10), non-neoplastic inflammatory lesions (NNUTD; n = 6), and no histologic changes (n = 11) were evaluated using immunohistochemistry. Blood NLRs were analyzed in dogs with UC (n = 22) or NNUTD (n = 26). RESULTS: Tissue S100A12-positive cell counts were significantly higher in dogs with lower urinary tract disease than healthy controls (P = 0.0267 for UC, P = 0.0049 for NNUTD), with no significant difference between UC and NNUTD patients. Tissue S100A8/A9-positivity appeared to be higher with NNUTD than UC, but this difference did not reach statistical significance. The S100A8/A9+-to-S100A12+ ratio was significantly decreased in neoplastic and inflamed lower urinary tract tissue compared to histologically normal specimens (P = 0.0062 for UC, P = 0.0030 for NNUTD). NLRs were significantly higher in dogs with UC than in dogs with NNUTD, and a cut-off NLR of ≤ 2.83 distinguished UC from NNUTD with 41% sensitivity and 100% specificity. Higher NLRs were also associated with a poor overall survival time (P = 0.0417). CONCLUSIONS: These results confirm that the S100/calgranulins play a role in the immune response to inflammatory and neoplastic lower urinary tract diseases in dogs, but the tissue expression of these proteins appears to differ from their concentrations reported in urine samples. Further investigations of the S100/calgranulin pathways in UC and their potential as diagnostic or prognostic tools and potential therapeutic targets are warranted. The NLR as a routinely available marker might be a useful surrogate to distinguish UC from inflammatory conditions.

The Impact of Selection for Facial Reduction in Dogs: Geometric Morphometric Analysis of Canine Cranial Shape.

Through artificial selection, humans have altered the morphology of domestic dogs and created the range of morphological traits present in the diverse dog breeds seen today. This article tests how artificial breeding for extreme facial reduction affects the craniodental complex in domestic dogs (Canis lupus familiaris). These brachycephalic dog breeds allow for a natural experiment on facial reduction, providing additional insight into this well-studied phenomenon associated with the evolutionary history of other animals including primates. We used an existing set of clinically obtained CT scans from dogs representing three brachycephalic breeds and a comparative sample. We recorded three-dimensional coordinate data for 62 cranial and mandibular landmarks that allowed us to analyze differences in shape in the neurocranium, basicranium, and viscerocranium. Through geometric morphometric analysis, we confirmed that most of the cranial shape variance in our sample was associated with cephalic index (cranial width-to-length ratio) and reflects the effects of facial reduction. Shape changes in the cranium and mandible co-vary. We also identified several areas of localized shape change. Whereas the primary shape change seen in the mandible is a uniform shift in proportion involving rostral-caudal shortening and medial-lateral widening, the majority of the shape change in the palate is localized to the maxilla. Here, a pronounced difference in maxillary carnassial orientation relative to the mandibular carnassials results in disruption of the functionally important carnassial complex. These results support previous studies showing integration within the skull and highlight the deleterious effects of artificial selection for extreme facial reduction in domestic dogs. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc. Anat Rec, 303:330-346, 2020. © 2019 American Association for Anatomy.

[Nasal discharge in dogs - are microbiological and histopathological examinations clinically useful?] / Nasenausfluss beim Hund ­ Wie sinnvoll sind bakteriologische und histopathologische Untersuchungen?

OBJECTIVE: Retrospective evaluation of the diagnostic value of bacterial culture of nasal mucosal swabs and histopathologic assessment of nasal mucosal biopsies in dogs with nasal discharge. MATERIAL AND METHODS: Medical records of dogs with the predominant clinical sign of nasal discharge that were referred to the ENT Unit of the Small Animal Department between January 2015 and December 2016 were reviewed. RESULTS: Data of 85 dogs were evaluated. On the basis of the results of computed tomography (CT), rhinoscopy, bacterial culture of a nasal mucosal swab and histopathologic examination of nasal mucosal biopsies, dogs were assigned to one of six groups of primary nasal diseases: nasal neoplasia (24/85, 28 %), oronasal defect (22/85, 26 %), idiopathic chronic rhinitis (17/85, 20 %), foreign body (8/85, 10 %), sinonasal aspergillosis (7/85, 8 %) and diseases of the planum nasale (7/85, 8 %). In brachycephalic dogs (14/85, 17 %), oronasal defects (8/14, 57 %) were the most frequent cause of nasal discharge. No cases of a primary bacterial infection of the nasal cavity were observed and, therefore, antibiotic treatment had not been successful. Nevertheless, 72 % of the dogs in this study had received prior antibiotic treatment. Secondary bacterial infec tions diagnosed via nasal mucosal swabs were not diagnostic for the underlying primary nasal diseases. Targeted biopsies of tumors obtained under endoscopic visualization may lead to a definitive diagnosis, whereas biopsies of the nasal mucosa and the type of the inflammatory infiltrate were not diagnostic. CONCLUSIONS: Nasal discharge in dogs is frequently an indicator of an underlying severe primary nasal disease possibly leading to mortality of the affected dogs. Further diagnostics under anesthesia should be performed early in the diagnostic evaluation. Rhinoscopy as the central diagnostic is supported by CT and biopsy. Bacterial culture of the nasal discharge does not provide a diagnosis for the primary nasal disease process. CLINICAL RELEVANCE: Without further diagnostics, antibiotic treatment of dogs presenting with nasal discharge is considered as not appropriate and can be harmful in dogs with nasal tumors or sinonasal aspergillosis. When an intranasal malignant neoplasia is suspected, endoscopic-guided biopsies of the nasal mass should be obtained, because blind nasal biopsies are associated with a high rate of false-negative results.

Tear glucose, creatinine, and urea nitrogen concentrations in cats with normal or increased plasma concentrations.

OBJECTIVE: The aim of the study was to determine the lacrimal fluid (LF) contents of glucose, urea nitrogen, and creatinine in cats. ANIMAL STUDIED: A total of 96 cats were included in the study. PROCEDURE: Venous blood and LF samples were collected. For LF sampling, three small polyurethane sponges were placed in the ventral fornix of both eyes. Both LF and plasma concentrations of glucose, urea nitrogen, and creatinine were quantitatively analyzed and compared. RESULT: Glucose (n = 40) and urea nitrogen concentrations (n = 42) measured in LF from both eyes highly correlated. While there was a very strong correlation (ρ = 0.97) between urea nitrogen concentrations in blood plasma and the corresponding tear levels (with the median LF urea nitrogen being 109% of that measured in plasma), the LF glucose concentrations were significantly lower than the corresponding plasma concentrations (with only 13% of the blood glucose concentration detected in the LF). The creatinine concentrations in tears were much lower than those in plasma, and LF creatinine was detectable in only 12/48 cats (25%). Hence, a comparison of the LF creatinine concentrations between both eyes or with the corresponding plasma creatinine concentration was not possible. CONCLUSION: Measurement of LF urea nitrogen concentrations in cats appears to be reliable and might have potential clinical utility. Measurement of LF glucose concentrations is less reliable but may still be useful in some cats. Creatinine is not reliably detected in the LF in cats. Further studies determining clinical utility of LF metabolites in cats and other companion animals are warranted.

Outcomes and prognostic factors of surgical treatments for brachycephalic obstructive airway syndrome in 3 breeds.

OBJECTIVE: To determine prognostic indicators for the surgical treatment of brachycephalic obstructive airway syndrome (BOAS) and to compare the prognosis of 2 multilevel surgical procedures. STUDY DESIGN: Prospective clinical study. SAMPLE POPULATION: Client-owned pugs, French bulldogs, and bulldogs (n = 50). METHODS: Noninvasive whole-body barometric plethysmography (WBBP) was used to assess respiratory function before, 1 month and 6 months after upper airway corrective surgery. Postoperatively, BOAS indices (ie, ascending severity score generated from WBBP data, 0%-100%) that equaled to or exceeded the cut-off values of BOAS in the diagnostic models were considered to have a "poor prognosis." A multivariate logistic regression was used to assess predictors for prognosis. RESULTS: The median BOAS indices decreased after surgery (from 76% to 63%, P < .0001), although dogs with indices in this range would still be considered clinically affected. Age (odds ratios [OR] = 0.96, 95% confidence interval [CI]: 0.93-0.99, P < .05), body condition (OR = 0.06, 95% CI: 0.01-0.39, P < .01), laryngeal collapse (OR = 6.1, 95% CI: 1-37.22, P < .05), and surgical techniques (OR = 7.94, 95% CI: 1.17-54.01, P < .05) were associated with postoperative prognosis. The multivariate model suggests modified multilevel surgery (MMS) may have a better outcome than traditional multilevel surgery (TMS) (P = .034). The positive predictive value of the logistic model was 84% (95% CI: 68-94%) and the area under the receiver operating characteristic (ROC) curve was 89% (95% CI: 78-99%, P <.0001). CONCLUSIONS: Younger age, normal body condition, presence of laryngeal collapse, and treatment with TMS were negative prognostic factors after surgical treatment of BOAS. MMS is recommended, particularly in dogs with a higher probability of poor prognosis.

A novel approach to brachycephalic syndrome. 3. Isolated laser-assisted turbinectomy of caudal aberrant turbinates (CAT LATE).

OBJECTIVE: To describe isolated laser-assisted turbinectomy of caudal aberrant turbinates (CAT LATE) as a new minimally invasive surgical procedure for the treatment of brachycephalic dogs with obstructing caudal aberrant turbinates (CAT). STUDY DESIGN: Prospective clinical study. ANIMALS: Brachycephalic dogs (24 Pugs, 1 English Bulldog) with CAT but adequate air spaces between the lamellae of the nonobstructing ventral nasal concha. METHODS: A rhinoscopically guided diode laser fiber introduced from anterior was used to dissect CAT within the nasopharyngeal meatus, while leaving the intranasal turbinates intact. Small grasping forceps were used to extract the dissected CAT from anterior or to push it through the nasopharyngeal meatus for extraction from posterior. RESULTS: Isolated CAT LATE was successfully performed on 32 CAT in 25 dogs. Intranasally applied xylometazoline helped shrink the ventral concha, making the approach and extraction easier. Minor bleeding was the only complication observed. CONCLUSION: It is possible to remove CAT with endoscopically applied diode-laser energy while leaving the nonobstructing ventral nasal concha intact.

How does multilevel upper airway surgery influence the lives of dogs with severe brachycephaly? Results of a structured pre- and postoperative owner questionnaire.

Brachycephalic airway syndrome in dogs is typified by a variety of anatomical abnormalities causing a diverse spectrum of clinical signs of varying intensity. This variability makes the assessment of the surgical outcome after upper airway surgery difficult. Using a structured questionnaire, the present study investigated the dog owner-perceived severity and frequency of a broad spectrum of welfare-relevant impairments 2 weeks before and 6 months after brachycephalic dogs underwent a recently developed multi-level upper airway surgery. All dogs underwent surgical treatment of stenotic nares (ala-vestibuloplasty), the nasal cavity (laser-assisted turbinectomy, LATE), the pharynx (palatoplasty and tonsillotomy), and if indicated, laryngeal surgery (laser-assisted ablation of everted ventricles and partial cuneiformectomy). Owners of brachycephalic dogs (n = 102) referred for upper airway surgery were eligible to participate. Questionnaire data from owners of 37 Pugs and 25 French bulldogs were evaluated. In all dogs, the clinical signs associated with brachycephaly improved markedly after surgery. Most encouraging was the striking reduction in life-threatening events by 90% (choking fits decreased from 60% to 5% and collapse from 27% to 3%). The incidence of sleeping problems decreased from 55% to 3%, and the occurrence of breathing sounds declined by approximately 50%. There was a marked improvement in exercise tolerance and a modest improvement in heat tolerance. Dogs with severe brachycephaly benefitted substantially from multi-level surgery, and there were particular improvements in the incidences of severe impairment and life-threatening events. However, despite the marked improvement perceived by dog owners, these dogs remained clinically affected and continued to show welfare-relevant impairments caused by these hereditary disorders.

A Novel Approach to Brachycephalic Syndrome. 1. Evaluation of Anatomical Intranasal Airway Obstruction.

OBJECTIVE: To evaluate airway obstruction due to abnormal intranasal anatomy in 3 brachycephalic dog breeds using computed tomography and rhinoscopy. STUDY DESIGN: Prospective clinical study. ANIMALS: A total of 132 brachycephalic dogs (66 Pugs, 55 French Bulldogs, and 11 English Bulldogs) with severe respiratory distress due to brachycephalic syndrome. METHODS: Computed tomography and anterior and posterior rhinoscopy were performed to evaluate endonasal obstruction. RESULTS: All dogs had abnormal conchal growth that obstructed the intranasal airways. Rostral aberrant turbinates (RAT) were common in Pugs (90.9%) but less frequent in French (56.4%) and English (36.4%) Bulldogs. Caudal aberrant turbinates (CAT) obstructing the nasopharyngeal meatus were commonly found in all breeds (66.7%). Deviation of the nasal septum was an almost consistent finding in Pugs (98.5%) but was less common in bulldogs. Obstructing turbinates had multiple points of mucosal contact responsible for obstruction of the intranasal airway. Interconchal and intraconchal mucosal contacts were evident in 91.7% of dogs. CONCLUSION: Selective breeding for short head conformation reduces the size of the nasal cavities to such an extent that intranasal structures grow aberrantly and malformed, leading to obstructed air conducting spaces. Intranasal airway obstruction of brachycephalic dogs may contribute to their exercise and heat intolerance because of impaired pulmonary ventilation and compromised thermoregulatory functions of the canine nose. Failure to address intranasal obstruction might be an explanation for lack of therapeutic success after conventional surgery for brachycephalic syndrome. Future consideration should be given to the diagnosis, management, and treatment of this newly described aspect of airway obstruction.

A Novel Approach to Brachycephalic Syndrome. 2. Laser-Assisted Turbinectomy (LATE).

OBJECTIVE: To introduce a new surgical procedure based on interventional, laser-assisted removal of obstructing turbinate tissue to improve endonasal airway patency in brachycephalic dogs and to confirm the short and long term results using computed tomography (CT) and rhinoscopy. STUDY DESIGN: Prospective clinical study. ANIMALS: Brachycephalic dogs (n = 158; 70 Pugs, 77 French Bulldogs, 11 English Bulldogs) referred for treatment of severe respiratory distress because of brachycephalic syndrome. METHODS: Computed tomography and anterior and posterior rhinoscopy were performed to evaluate endonasal obstruction. Laser-assisted turbinectomy (LATE) using a diode laser was performed as part of a multilevel surgery. Nasal conchae that were causing airway obstruction were removed. RESULTS: The obstructing parts of the conchae were safely and efficiently removed by LATE, shaping a patent nasal airway in all dogs. The newly developed surgical procedure involved 3 steps: turbinectomy of the (1) concha nasalis ventralis; (2) rostral aberrantly growing turbinates (RAT); and (3) caudal aberrantly growing turbinates (CAT). Complications of the procedure included transient intraoperative hemorrhage in 51 of 158 dogs (32.3%); however, a temporary tamponade was necessary in only 2/158 dogs (1.3%). After 6 months, regrowth of turbinates required resection of possibly re-obstructing tissue in 25/158 dogs (15.8%; 1 Pug and 24 French Bulldogs). CONCLUSION: LATE is an effective method for creating a patent nasal airway in brachycephalic dogs with intranasal obstruction.

Inside the brachycephalic nose: intranasal mucosal contact points.

The purpose of this study was to evaluate the prevalence of intranasal mucosal contact points in brachycephalic and normocephalic dogs. In total, 82 brachycephalic dogs (42 pugs and 40 French bulldogs) were evaluated by rhinoscopy for their intranasal mucosal contact and 25 normocephalic dogs were evaluated as a control group. Of those, 162 brachycephalic nasal cavities were evaluable and 140 had contact between intranasal structures (87%). Intraconchal and septoconchal mucosal contact points were the most commonly detected sites of contact. French bulldogs had a significantly higher prevalence of mucosal contact and had 3 mean contact points compared with 1.7 mean contact points per nasal cavity in pugs. Septal deviations were present in 62% of brachycephalic dogs. In the control group, mucosal contact points were present in only 7 of 50 nasal cavities (14%), and septal deviations occurred in 16% of those cases. Contact point average was 0.1 in large and 0.3 in small normocephalic dogs. Intranasal mucosal contact was identified as a common and previously unreported problem in brachycephalic dogs. Numerous contact points reduce the lumen of the intranasal passageways and indicate potential intranasal obstruction. Affected dogs might benefit from removal of obstructing conchae, potentially using laser-assisted turbinectomy.

How does severe brachycephaly affect dog's lives? Results of a structured preoperative owner questionnaire.

Brachycephalic syndrome (BS) is a complex canine disease, which is characterized by diverse clinical signs primarily involving the respiratory and gastrointestinal systems. Through a structured owner questionnaire, the present study investigated how owners perceived the frequency and severity of a broad spectrum of welfare-relevant impairments caused by this hereditary disease. One hundred owners of brachycephalic dogs (Pugs and French bulldogs) referred for surgical treatment of BS completed the questionnaire. As a basis for comparison, 20 owners of mesocephalic dogs also completed part of the questionnaire. Questionnaire responses revealed that in addition to the well-known respiratory signs, brachycephalic dogs experienced severe exercise intolerance and prolonged recovery time after physical exercise (88%), significant heat sensitivity (more severe signs at temperatures above 19°C; 50%) and a variety of sleep problems (56%). To our knowledge, this is the first study using a structured owner questionnaire specifically to investigate a broad range of problems caused by selective breeding for brachycephaly. In particular, decreased exercise tolerance, increased recovery time due to heat intolerance and the extent of sleep problems have either been underestimated in the past, or have severely worsened over recent generations of dogs. The extent and severity of clinical signs and their impact on quality of life greatly exceeded our expectations. This study emphasizes the major impact that selective breeding for extreme brachycephalic features has on animal welfare.

A new incision technique to reduce tibiofemoral mismatch in rotationplasty.

Rotationplasty provides stable and durable biologic reconstruction after tumor resection around the knee and renders reliable results, in young patients. However, after resection of the tumor, there is often a mismatch between the circumference of the proximal (femoral) and the distal (tibial) parts. Because rotationplasty includes an intercalary amputation where the ends are readapted, there is always a mismatch of the proximal and distal circumferences of the soft tissue envelope. To facilitate skin closure without tension and to avoid impaired wound healing and subsequent infections, the type of incision is critical and must be carefully planned. We present a new incision technique for rotationplasty about the knee. Half of the difference of the incision length of the proximal and distal circumferences represents the base of the triangle proximally, medially and laterally of the thigh. After adapting both ends, the peak of this flat triangle is distally adapted via a vertical incision which allows it to match unequal circumferences. This technique was used in eight patients, in all of whom the wounds healed uneventfully.

Brachycephalic feline noses: CT and anatomical study of the relationship between head conformation and the nasolacrimal drainage system.

AIMS: A study was designed to evaluate the influence of head conformation on the course of the nasolacrimal drainage system (NDS) in 31 brachycephalic and 15 mesocephalic cats using computed tomography (CT), CT-dacryocystography and anatomical methods. FINDINGS: The higher the degree of brachycephalia, the more the facial bones and upper canine teeth are displaced dorsally (ie, the more pronounced the dorsorotation). Dorsorotation leads to abnormal dislocation of the ventral nasal concha and to almost horizontally rotated upper canine teeth, and thus a steeply oriented NDS. In severe brachycephalia the NDS is forced to pass below the canine tooth (adopt a V-shaped course) and the drainage function seems to be inefficient. PRACTICAL RELEVANCE: The rotation of the upper canine teeth appears to provide a basis for classification of brachycephalia in cats. The authors recommend that breeders avoid breeding from individuals affected by this condition and to give preference to cats with longer facial bones.

Computed tomography of the lungs of Indian pythons (Python molurus).

OBJECTIVE: To evaluate the use of computed tomography (CT) for detection of pneumonia in snakes. ANIMALS: 8 clinically normal Indian pythons (Python molurus) and 5 pythons with evidence of respiratory tract disease. PROCEDURES: Preliminary examinations (clinical examination, conventional radiography, and microbiologic examination of a transtracheal wash sample) were performed. The lungs of each snake were then examined by use of CT performed in accordance with a standardized protocol. Structures of the lungs were assessed, and thickness and attenuation of the parenchyma were determined. RESULTS: It was possible to assess lung parenchyma in all pythons. Mean +/- SD attenuation in healthy pythons was -744.4 +/- 47.1 Hounsfield units. Significant differences were not evident between the right and left lungs or among measurement areas within a lung. In all Indian pythons with clinical signs of dyspnea and microbiologic detection of pathogens, hyperattenuation of the alveolar tissue was evident. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the results revealed the benefit of CT for use in the diagnosis of pneumonia in snakes. A standardized protocol and reference values were established as a basis for CT assessment of the lungs of snakes.

[Rudolf Lemke's contribution to the development of child neuropsychiatry in Jena, Germany]. / Rudolf Lemkes Bedeutung für die Entwicklung der Kinderneuropsychiatrie in Jena.

Child and adolescent psychiatry has a long tradition in Jena, Germany, and goes back to the psychiatrists Theodor Ziehen and Wilhelm Strohmayer. It seems that Rudolf Lemke (1906-1957) eminently promoted the development of child and adolescent psychiatry after World War II. A versatile scientist, Lemke had many publications in psychiatric and neurologic fields. His significance to the development of the specialty of child and adolescent psychiatry is reflected not only by his publications but also by his work as a clinician and liaison psychiatrist in the Johannes Trueper School in Jena. He founded an independent psychiatric unit for the treatment of children which allowed treatment separated from adults.

The contralateral foot in children with unilateral clubfoot: a study of pressures and forces involved in gait.

The unaffected contralateral side of patients with unilateral clubfeet has sometimes been taken as control in foot pressure measurement studies. However, it has never been shown that the pressure pattern under the contralateral foot is similar to a normal foot. Sixteen patients with unilateral clubfoot and 110 normal subjects took part in this study. All participants were aged from 4 to 8 years. Studies comprised clinical examination and foot pressure measurements in barefoot walking. Evaluations of the measurements were completed by the calculation of forces acting under 10 anatomical foot areas normalized to ground reaction force at foot-flat and push-off. Significant differences in peak pressure were observed between the control group and the contralateral foot of patients under the heel and the metatarsals 1 to 4. Significant differences in the forces at foot-flat and push-off are seen especially in the midfoot. Both sides of the patients with unilateral clubfeet exert significantly less ground reaction force than normal subjects. Different pressure and force distributions of clubfoot children on their contralateral side compared with the normal feet of the control group may indicate differences in the general control pattern generated by the central nervous system. Differences can still be observed after normalization of the forces. We therefore conclude that when foot pressure measurements are made with clubfeet, it might be advisable to use a collective of normal feet, instead of the contralateral foot, for comparison.

["If Berger had survived the second world war - he certainly would have been a candidate for the Nobel Prize". Hans Berger and the legend of the Nobel Prize]. / "Hätte Berger das Ende des zweiten Weltkrieges noch erlebt -- gewiss wäre er ein Anwärter auf den Nobelpreis geworden" -- Ein Beitrag zum 200. Jahrestag der Gründung der Jenaer Psychiatrischen Klinik.

The public opinion pays much attention to the Nobel Prize as an indicator for the scientific efficiency of a university or a country in connection with foundation of so-called elite universities. The former holder of the psychiatric chair in Jena and discoverer of the electroencephalogram Hans Berger (1873 - 1941) came into discussion as candidate for the Nobel Prize in physiology or medicine. The current medical-historical publications maintain the view that Berger should have received the Nobel Prize in 1936 as well as in 1949. This was prevented in 1936 by an enactment from Hitler, which forbid him to accept the prize, and later in 1949 by Berger's own death. According to documents of the Nobel archives these statements can be disproved. Berger was only nominated three times out of 65 nominations in 1940. Because of his death the other two recommendations in 1942 and 1947 were never evaluated.