Noninferiority of Artificial Intelligence-Assisted Analysis of Ki-67 and Estrogen/Progesterone Receptor in Breast Cancer Routine Diagnostics.

Image analysis assistance with artificial intelligence (AI) has become one of the great promises over recent years in pathology, with many scientific studies being published each year. Nonetheless, and perhaps surprisingly, only few image AI systems are already in routine clinical use. A major reason for this is the missing validation of the robustness of many AI systems: beyond a narrow context, the large variability in digital images due to differences in preanalytical laboratory procedures, staining procedures, and scanners can be challenging for the subsequent image analysis. Resulting faulty AI analysis may bias the pathologist and contribute to incorrect diagnoses and, therefore, may lead to inappropriate therapy or prognosis. In this study, a pretrained AI assistance tool for the quantification of Ki-67, estrogen receptor (ER), and progesterone receptor (PR) in breast cancer was evaluated within a realistic study set representative of clinical routine on a total of 204 slides (72 Ki-67, 66 ER, and 66 PR slides). This represents the cohort with the largest image variance for AI tool evaluation to date, including 3 staining systems, 5 whole-slide scanners, and 1 microscope camera. These routine cases were collected without manual preselection and analyzed by 10 participant pathologists from 8 sites. Agreement rates for individual pathologists were found to be 87.6% for Ki-67 and 89.4% for ER/PR, respectively, between scoring with and without the assistance of the AI tool regarding clinical categories. Individual AI analysis results were confirmed by the majority of pathologists in 95.8% of Ki-67 cases and 93.2% of ER/PR cases. The statistical analysis provides evidence for high interobserver variance between pathologists (Krippendorff's α, 0.69) in conventional immunohistochemical quantification. Pathologist agreement increased slightly when using AI support (Krippendorff α, 0.72). Agreement rates of pathologist scores with and without AI assistance provide evidence for the reliability of immunohistochemical scoring with the support of the investigated AI tool under a large number of environmental variables that influence the quality of the diagnosed tissue images.

Fallbericht über eine an COVID-19 erkrankte Patientin mit bestehendem Schmerzsyndrom.

CASE REPORT: Patient with COVID-19 and pre-existing pain syndrome Abstract. Background: This paper focuses on the case study of a patient in the UK who showed - as far as we know today - all typical symptoms of an infection with SARS-CoV-2 but without dyspnoea. The diagnose was made on the basis of the symptoms, which were described by the patient, and confirmed by an antibody test in August 2020. Aim: Due to the public interest in knowing more about the cluster of symptoms and their implications for nursing, the patient and the author of this paper decided to present this case study to the professional audience. Methods: For the anamnesis, the patient's COVID-19 diary and an essay by her about her experiences with the National Health Service (NHS) were analysed and completed by information collected during a structured interview. Results: It became apparent that the nursing diagnoses "Acute pain" and "Chronic pain" stand at the forefront. These nursing diagnoses have not been discussed in the context of COVID-19 yet. Conclusions: This leads to the conclusion that nursing diagnoses, which are orientated towards an alleged lung disease, might not be complete when it comes to the complex disease process of COVID-19. Furthermore, this case example highlights the difficulties faced by the UK health system.

Instant evaluation of contrast enhanced endoscopic ultrasound helps to differentiate various solid pancreatic lesions in daily routine.

BACKGROUND: Contrast enhanced harmonic endoscopic ultrasound (CEH-EUS) is a spreading technique; some studies have shown its value in the diagnosis of pancreatic adenocarcinoma using quantitative analysis. AIM: To examine the value of CEH-EUS for differentiating various pancreatic lesions in everyday routine with qualitative and quantitative analysis. METHODS: Data of 55 patients with pancreatic lesions who underwent CEH-EUS were analysed retrospectively. Perfusion characteristics were classified by the investigator qualitatively immediately upon investigation, quantitative analysis was performed later on. Samples from fine needle aspiration (EUS-FNA) or surgical specimen served as gold standard. RESULTS: CEH-EUS showed 39 hypoenhanced lesions, 3 non-enhanced and 13 hyperenhanced lesions. Concordance of the investigators qualitative classification of peak contrast enhancement with quantitative analysis later on was 100%, while other parameters such as arrival time, time to peak or area under the curve did not show additional value. 34 of 39 hypoenhanced lesions were pancreatic adenocarcinoma; of the hyperenhanced lesions 4 were inflammatory, 3 neuroendocrine carcinomas, 1 lymphoma, 1 insulinoma and 4 metastases (2 of renal cell carcinoma, 2 of lung cancer). Non-enhanced lesions showed up as necroses. Sensitivity for the detection of pancreatic adenocarcinoma was 100%, specificity 87.2% for hypoenhancement alone; in otherwise healthy pancreatic tissue all hypoenhanced lesions were pancreatic adenocarcinoma (sensitivity and specificity 100%, PPV and NPV for adenocarcinoma 100%). CONCLUSION: This study again shows the excellent value of CEH-EUS in everyday routine for diagnostics of various focal pancreatic lesions suggesting that qualitatively assessed hypoenhancement is highly predictive for adenocarcinoma. Additional quantitative analysis of perfusion parameters does not add diagnostic yield. In case of the various hyperenhanced pancreatic lesions in our data set, histologic sampling is essential for further treatment.

Papillary Thyroid Cancer and Coexisting Autoimmune Thyroiditis.

Histological findings often display an association between papillary thyroid carcinomas (PTC) and autoimmune thyroiditis (AIT) and so differ significantly from follicular thyroid carcinomas (FTC). The aim of this interdisciplinary, retrospective study was to evaluate the association of AIT in patients with PTC and FTC and a control group of benign nodular goiters. One hundred thyroidectomies with histologically confirmed differentiated thyroid carcinomas, 67 with PTC and 33 with FTC, were submitted for examination. The two control groups consisted of 60 patients with euthyroid nodular goiter, displaying no signs for malignancy (no surgery) and 100 patients (second control group) with surgery of a benign nodular goiter. Controls were collected to obtain data about the incidence of significantly increased TPOAbs in the first group and of lymphocytic infiltrates (LI) in the second group. High TPOAbs were found in 35% (23/67) of patients with PTC. LI were detected by histology in 48% (32/67) of PTC. Ten patients (10/32) of this group showed the clinical and histological manifestation of a classic AIT with diffuse dense LI as well as diffuse hypoechogeneity in ultrasonography. In 7/32 cases, the histological report described focal dense LI (fAIT) and in 15/32 cases scant scattered LI. AIT and fAIT, together 25% of all PTC (17/67), showed germinal centers and can therefore be characterized as chronic autoimmune thyroiditis. In this group, high TPOAb could be detected in 94% (16/17). Scan scattered LI without germinal centers (15/32) do not represent a fAIT, although TPOAb are high in 47% (7/15). The younger age group (<45 years) showed significantly more often high TPOAbs (p<0.023) in comparison with the age-group older than 60 years. In contrast to PTC, only 4/33 (12%) patients with FTC had high TPOAb levels. We conclude that in contrast to benign euthyroid goiters and to FTC, different degrees of LI are often associated with high TPOAb levels and seem to be significantly increased in PTC, particularly prominent in younger age. There is a high coincidence between LI and high TPOAb levels. In the presence of hypoechoic thyroid nodule, signs of thyroid autoimmunity such as the presence of high TPOAbs, lymphocytic infiltration in cytology, and/or characteristic ultrasonic features, are arguments that might favor the decision for surgery if a cytologically indeterminate thyroid nodule is found and focal autonomy is excluded by szintiscan.

In-situ tissue regeneration through SDF-1α driven cell recruitment and stiffness-mediated bone regeneration in a critical-sized segmental femoral defect.

In-situ tissue regeneration aims to utilize the body's endogenous healing capacity through the recruitment of host stem or progenitor cells to an injury site. Stromal cell-derived factor-1α (SDF-1α) is widely discussed as a potent chemoattractant. Here we use a cell-free biomaterial-based approach to (i) deliver SDF-1α for the recruitment of endogenous bone marrow-derived stromal cells (BMSC) into a critical-sized segmental femoral defect in rats and to (ii) induce hydrogel stiffness-mediated osteogenic differentiation in-vivo. Ionically crosslinked alginate hydrogels with a stiffness optimized for osteogenic differentiation were used. Fast-degrading porogens were incorporated to impart a macroporous architecture that facilitates host cell invasion. Endogenous cell recruitment to the defect site was successfully triggered through the controlled release of SDF-1α. A trend for increased bone volume fraction (BV/TV) and a significantly higher bone mineral density (BMD) were observed for gels loaded with SDF-1α, compared to empty gels at two weeks. A trend was also observed, albeit not statistically significant, towards matrix stiffness influencing BV/TV and BMD at two weeks. However, over a six week time-frame, these effects were insufficient for bone bridging of a segmental femoral defect. While mechanical cues combined with ex-vivo cell encapsulation have been shown to have an effect in the regeneration of less demanding in-vivo models, such as cranial defects of nude rats, they are not sufficient for a SDF-1α mediated in-situ regeneration approach in segmental femoral defects of immunocompetent rats, suggesting that additional osteogenic cues may also be required. STATEMENT OF SIGNIFICANCE: Stromal cell-derived factor-1α (SDF-1α) is a chemoattractant used to recruit host cells for tissue regeneration. The concept that matrix stiffness can direct mesenchymal stromal cell (MSC) differentiation into various lineages was described a decade ago using in-vitro experiments. Recently, alginate hydrogels with an optimized stiffness and ex-vivo encapsulated MSCs were shown to have an effect in the regeneration of skull defects of nude rats. Here, we apply this material system, loaded with SDF-1α and without encapsulated MSCs, to (i) recruit endogenous cells and (ii) induce stiffness-mediated osteogenic differentiation in-vivo, using as model system a load-bearing femoral defect in immunocompetent rats. While a cell-free approach is of great interest from a translational perspective, the current limitations are described.

Effect of exogenous fibrolytic enzymes on performance and blood profile in early and mid-lactation Holstein cows.

The supplementation of exogenous fibrolytic enzymes (EFE) to dairy cows diets could be a strategy to improve fiber degradation in the rumen which is especially important for the early lactating cows characterized by a high milk energy output and an insufficient energy intake. The objective of this study was to examine the effects of a fibrolytic enzyme product (Roxazyme G2 Liquid, 3.8 and 3.9 mL/kg total mixed ration [TMR] DM) supplemented to a TMR on production performance and blood parameters of dairy cows during early (trial 1) and mid-lactation (trail 2). In addition, rumination activity was measured in trial 2. The nutrient digestibility of the experimental TMR was obtained by using wethers. In the digestibility trial, EFE was supplemented at a rate of 4.4 mL/kg Roxazyme G2 Liquid TMR-DM. The TMR contained 60% forage and 40% concentrate (DM basis). Twenty eight 50 ± 16 days in milk (DIM) and twenty six 136 ± 26 DIM Holstein cows were used in two 8-wk completely randomized trails, stratified by parity and milk yield level. One milliliter of the enzyme product contained primarily cellulase and xylanase activities (8,000 units endo-1,4-ß glucanase, 18,000 units endo-1,3(4)-ß glucanase and 26,000 units 1,4-ß xylanase). No differences in digestibility of DM, OM, CP, NDF and ADF were observed (P > 0.05) between the control and the EFE supplemented TMR. Addition of EFE to the TMR fed to early (trial 1) and mid-lactation cows (trial 2) did not affect daily dry matter intake (DMI), milk yield, 4% fat-corrected milk, energy-corrected milk (ECM), concentration of milk fat, protein, fat-protein-quotients, somatic cell score, energy balance, and gross feed efficiency of early and mid-lactation cows (P > 0.05). Mid-lactation cows (trial 2) fed with TMR enzyme showed a tendency of a slightly higher ECM yield (P = 0.09). The tested blood parameters were not affected by treatment in trials 1 and 2 (P > 0.05). Exogenous fibrolytic enzymes supplementation did not alter daily time spent ruminating in trial 2 (P = 0.44). In conclusion, under the conditions of this study, no positive effects of enzyme supplementation on dairy performance and health status of dairy cows during early and mid-lactation were observed.

Force-feeding is in the interests of the state, not its prisoners.

Further to Paul Hegarty's letter, 'Force-feeding is wrong and nurses should play no part' (July 30), the International Council of Nurses is clear about the role of nurses.

One night of partial sleep deprivation affects habituation of hypothalamus and skin conductance responses.

Sleep disturbances are prevalent in clinical anxiety, but it remains unclear whether they are cause and/or consequence of this condition. Fear conditioning constitutes a valid laboratory model for the acquisition of normal and pathological anxiety. To explore the relationship between disturbed sleep and anxiety in more detail, the present study evaluated the effect of partial sleep deprivation (SD) on fear conditioning in healthy individuals. The neural correlates of 1) nonassociative learning and physiological processing and 2) associative learning (differential fear conditioning) were addressed. Measurements entailed simultaneous functional MRI, EEG, skin conductance response (SCR), and pulse recordings. Regarding nonassociative learning, partial SD resulted in a generalized failure to habituate during fear conditioning, as evidenced by reduced habituation of SCR and hypothalamus responses to all stimuli. Furthermore, SCR and hypothalamus activity were correlated, supporting their functional relationship. Regarding associative learning, effects of partial SD on the acquisition of conditioned fear were weaker and did not reach statistical significance. The hypothalamus plays an integral role in the regulation of sleep and autonomic arousal. Thus sleep disturbances may play a causal role in the development of normal and possibly pathological fear by increasing the susceptibility of the sympathetic nervous system to stressful experiences.

Contrast-enhanced harmonic endoscopic ultrasound is able to discriminate benign submucosal lesions from gastrointestinal stromal tumors.

BACKGROUND: Although endoscopic ultrasound (EUS) has improved the diagnostic of potential malignancies, gastric lesions with suspicion of gastrointestinal stromal tumors (GIST) or benign lesions like lipoma or leiomyoma can often not be accurately differentiated by EUS, therefore, requiring tissue sampling with the risk of bleeding complications especially in GIST. As with the newest generation of EUS machines, contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) has become a new option to determine perfusion characteristics. The aim of this analysis was to evaluate whether CEH-EUS may help to discriminate various submucosal lesions. METHODS: Data sets of 17 patients with suspicious gastric or esophageal lesions, who were investigated with CEH-EUS were analyzed. Perfusion characteristics were classified by the investigator immediately and statistically analyzed after investigation. Samples from EUS-fine needle aspirates, biopsy samples after needle cut or surgical specimen served as gold standard. RESULTS: CEH-EUS showed nine lesions with reduced contrast enhancement (maximum intensity 6.2 ± 1.9 db) and eight lesions with hyperenhancement (47.3 ± 11.6 db). The latter eight lesions were all histologically identified as GIST, while the nine hypoenhanced lesions emerged to be four lipoma and five leiomyoma. Statistical analysis corresponded with initial perfusion classification in all cases. CONCLUSION: This is the first study showing that CEH-EUS can discriminate GIST from benign lesions with good accuracy. In the future, CEH-EUS-guided discrimination may lead to individualized diagnostic and therapeutic strategies in handling submucosal lesions.

[Sterilization surgeon and researcher: life and career of Benno Ottow (1884-1975)]. / Sterilisierungsoperateur und Forscher: Leben und Karriere Benno Ottows (1884-1975).

The activities of the gynaecologist and member of the Erbgesundheitsgericht Benno Ottow (1884-1975) in the "Third Reich" have been described in a couple of publications. During the Nazi dictatorship Ottow demonstrated great commitment to putting the ideological and legal demands into practice. Drawing on sources from private and state archives in Estonia, Germany and Sweden, this paper investigates the biography of Benno Ottow: from his time as a junior physician period in Estonia and Russia to his directorship of the Brandenburg gynaecological state hospital in Berlin-Neukölln and the postwar-years in Sweden.

A 5-mm femoral defect in female but not in male rats leads to a reproducible atrophic non-union.

INTRODUCTION: The objectives of this study were to (1) establish a reproducible atrophic non-union model in rats by creation of a segmental femoral bone defect that allows, (2) in-depth characterization of impaired healing, and (3) contrast its healing patterns to the normal course. Hypothesis was that a 5-mm bone defect in male rats would deviate from uneventful healing patterns and result in an atrophic non-union. MATERIALS AND METHODS: A femoral osteotomy was performed in two groups of 12-week-old male rats (1 vs. 5 mm gap) stabilized with an external fixator. Bone healing in these models was evaluated by radiology, biomechanics, and histology at 6 or 8 weeks. The evaluation of the 5-mm group revealed in some cases a delayed rather than a non-union, and therefore, a group of female counterparts was included. RESULTS: The creation of a 5-mm defect in female rats resulted in a reproducible atrophic non-union characterized by sealing of the medullary canal, lack of cartilage formation, and negligible mechanical properties of the callus. In both gap size models, the male subjects showed advanced healing compared to females. DISCUSSION AND CONCLUSION: This study showed that even under uneventful healing conditions in terms of age and bone defect size, there is a sex-specific advanced healing in male compared to female subjects. Contrary to our initial hypothesis, only the creation of a 5-mm segmental femoral defect in female rats led to a reproducible atrophic non-union. It has been shown that an atrophic non-union exhibits different healing patterns compared to uneventful healing. A total lack of endochondral bone formation, soft tissue prolapse into the defect, and bony closure of the medullary cavity have been shown to occur in the non-union model.

Standard bone healing stages occur during delayed bone healing, albeit with a different temporal onset and spatial distribution of callus tissues.

Bone healing is considered as a recapitulation of a developmental program initiated at the time of injury. This study tested the hypothesis that in delayed bone healing the regular cascade of healing events, including remodeling of woven to lamellar bone, would be similar compared to standard healing, although the temporal onset would be delayed. A tibial osteotomy was performed in sheep and stabilized with a rotationally unstable fixator leading to delayed healing. The sheep were sacrificed at 2, 3, 6, 9 weeks and 6 months postoperatively. The temporal and spatial tissue distributions in the calluses and the bone microstructure were examined by histology. Although histological analysis demonstrated temporal and spatial callus tissue distribution differences, delayed healing exhibited the same characteristic stages as those seen during uneventful standard healing. The delayed healing process was characterized by a prolonged presence of hematoma, a different spatial distribution of new bone and delayed and prolonged endochondral bone formation. A change in the spatial distribution of callus formation was seen by week 6 leading to bone formation and resorption of the cortical bone fragments, dependent on the degree to which the cortical bone fragments were dislocated. At 6 months, only 5 out of 8 animals showed complete bony bridging with a continuous periosteum, although lamellar bone and newly formed woven bone were present in the other 3 animals. This study demonstrates that during delayed bone healing all stages of the healing cascade likely take place, even if bony consolidation does not occur. Furthermore, the healing outcome might be related to the periosteum's regenerative capacity leading to bony union or absence of bony bridging.

Effect of exogenous fibrolytic enzymes on ruminal fermentation and nutrient digestion in dairy cows.

The aim of the present study was to examine the effects of an exogenous fibrolytic enzyme product applied to a total mixed ration (TMR) prior to feeding on ruminal fermentation, microbial protein synthesis, nutrient digestion, and milk yield and composition. Six multiparous lactating Holstein cows (598 +/- 29 kg initial live weight and 98 +/- 30 days in milk) fitted with rumen and duodenal cannulae were allocated to two treatments in a crossover design over three consecutive 28-d periods. The TMR containing 50% concentrates, 30% corn silage and 20% grass silage on dry matter (DM) basis, was mixed once daily and fed twice a day. Treatments were TMR alone (Control) or TMR with an enzyme product containing primarily cellulase and xylanase activities (9000 U endo-1,4-beta glucanase, 24000 U endo-1,3(4)-beta glucanase and 40000 U 1,4-beta xylanase per ml). The enzyme product was applied at a rate of 6.2 ml/kg TMR (DM basis). It was diluted at a rate of 1:5 with water and applied daily to the TMR. During the control period the cows received a TMR supplemented with 36 ml water/kg TMR on DM basis. Duodenal digesta flow was measured using Cr2O3 as flow marker and microbial protein in the duodenal digesta was estimated by near-infrared spectroscopy (NIRS). There were no significant differences in ruminal pH-values, NH3-N concentrations, total SCFA concentrations and molar proportions of SCFA. No treatment effects on microbial N flow to the duodenum and efficiency of microbial protein synthesis were observed. The apparent ruminal digestibilities of DM, organic matter, NDF and ADF, milk yield and composition were also not affected by the enzyme supplementation. In this study the application of exogenous fibrolytic enzymes fed to dairy cows did not show a significant effect on any parameter tested.

Insight into the molecular pathophysiology of delayed bone healing in a sheep model.

Delayed and nonunions are still challenging problems. In this study, we examined the endogenous mRNA expression of genes regulating cartilage formation, bone formation, endochondral ossification, and bone remodeling during mechanically induced delayed bone healing in a large animal model. A tibial osteotomy was performed in two groups of sheep and stabilized with either a rigid external fixator leading to standard healing or with a rotationally unstable fixator leading to delayed healing. At days 4, 7, 9, 11, 14, 21, and 42 after surgery, total RNA was extracted from the callus. Gene expressions of several molecules functionally important for bone healing were studied by quantitative reverse transcriptase-polymerase chain reaction. The expression profiles were related to callus tissue composition, analyzed by histomorphometry. Histomorphometry demonstrated a delayed, prolonged chondral phase and a reduction in bone formation in the experimental group. There was no differential expression of Runx2 between both groups until day 42, but mRNA expression levels of BMP2, BMP4, BMP7, noggin, Col1a1, IGF1, TGFbeta1, OPN, MMP9, MMP13, TIMP3, TNFalpha, MCSF, RANKL, and OPG were lower in the delayed healing group at several time points. This study provides insight into the temporal periods during which various factors may be deficient during a compromised bone-healing situation.

Differential regulation of blood vessel formation between standard and delayed bone healing.

Blood vessel formation is a prerequisite for bone healing. In this study, we tested the hypothesis that a delay in bone healing is associated with an altered regulation of blood vessel formation. A tibial osteotomy was performed in two groups of sheep and stabilized with either a rigid external fixator leading to standard healing or with a highly rotationally unstable one leading to delayed healing. At days 4, 7, 9, 11, 14, 21, and 42 after surgery, total RNA was extracted from the callus. Gene expressions of vWF, an endothelial cell marker, and of several molecules related to blood vessel formation were studied by qPCR. Furthermore, histology was performed on fracture hematoma and callus sections. Histologically, the first blood vessels were detected at day 7 in both groups. mRNA expression levels of vWF, Ang1, Ang2, VEGF, CYR61, FGF2, MMP2, and TIMP1 were distinctly lower in the delayed compared to the standard healing group at several time points. Based on differential expression patterns, days 7 and 21 postoperatively were revealed to be essential time points for vascularization of the ovine fracture callus. This work demonstrates for the first time a differential regulation of blood vessel formation between standard and mechanically induced delayed healing in a sheep osteotomy model.

Locally applied osteogenic predifferentiated progenitor cells are more effective than undifferentiated mesenchymal stem cells in the treatment of delayed bone healing.

Mesenchymal stem cells (MSCs) and osteogenic predifferentiated cells (OPCs) have been shown to promote healing of critical-sized bone defects. This study investigated the regenerative capacity of autologous MSCs versus OPCs after local injection into a compromised bone healing situation. We hypothesized that treatment with MSCs and OPCs would enhance the healing and that the MSCs would be more effective due to their lower differentiation and higher proliferative competence. The femur of rats was osteotomized and stabilized with an external fixator. Except for the control group (C group), in all animals a delayed healing was induced by cautering the periosteum and removing the bone marrow. Two days postsurgery, autologous MSCs (MSC group), OPCs (OPC group), or cell-free medium (Sham group) was percutaneously injected into the osteotomy gap. The C group received no treatment. Bone healing was evaluated radiologically, biomechanically, and histologically. After 8 weeks, the C group showed complete bony bridging, while a delayed healing was detected in the Sham group. All outcome measures showed better healing of the OPC group compared to the Sham group. Contrary to our expectations, there were no significant differences in outcome measures between the MSC group and the Sham group. The percutaneous injection of OPCs could become a minimally invasive treatment option for delayed or nonunions.

A quarter century of the analysis of verbal behavior: an analysis of impact.

The Analysis of Verbal Behavior (TAVB) has been published since 1982, and during this time, interest in verbal behavior research appears to have increased substantially within behavior analysis. The purpose of the present analysis was to assess the influence of TAVB on the field by (a) counting citations of TAVB articles in the Journal of the Experimental Analysis of Behavior (JEAB) and the Journal of Applied Behavior Analysis (JABA) from 1983 through 2007, (b) examining which other journals cite TAVB, and (c) calculating impact-factor estimates for 2003 through 2007. Citations of TAVB articles began to appear in JEAB and JABA in the late 1980s to early 1990s, and by the end of 2007, almost a third of all articles published in TAVB had been cited in either JEAB or JABA. Other journals that cite TAVB include The Behavior Analyst and The Psychological Record. The estimated impact factor ranged from 0.267 to 0.600. Strategies for increasing the impact of TAVB are discussed.

'Arzteführerschule Alt-Rehse'--the main educational centre for promotion of Nazi medicine ideology in Germany during 1935 - 1943.

In Nazi Germany 1933-1945 the medical profession played an important role, not only within the health sector but also for ideological purposes. Some physicians committed criminal acts during the war, for example in concentration camps, and where later put on trial at the Nuremberg Trials in 1946-1947, some of them also sentenced to death. What is little known outside Germany is the existence of a specialised political leader school for physicians, dentists, midwives, pharmacists, and health officials at Alt-Rehse, a small village north of Berlin in the province of Mecklenburg, Northern Germany. Supported by historical documents it can be shown that the ideological training at Alt-Rehse was structured, politically effective, and well appreciated by the many attending students visiting the school. There is reason to believe that former Alt-Rehse students took part in Nazi criminal acts of war, but this is hard to prove as all documents were captured by the Russian Army at the end of the Second World War and have until now not been traced. Documents have shown that also many foreign visitors came to Alt-Rehse, from the UK, Sweden, Japan, and other countries during the pre-war years. The lessons from Alt-Rehse include how a totalitarian ideology can shape the professional role of health workers.