Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance.

Removal of micropollutants with coarse-ground activated carbon for enhanced separation with hydrocyclone classifiers.

One key technology to eliminate organic micropollutants (OMP) from wastewater effluent is adsorption using powdered activated carbon (PAC). To avoid a discharge of highly loaded PAC particles into natural water bodies a separation stage has to be implemented. Commonly large settling tanks and flocculation filters with the application of coagulants and flocculation aids are used. In this study, a multi-hydrocyclone classifier with a downstream cloth filter has been investigated on a pilot plant as a space-saving alternative with no need for a dosing of chemical additives. To improve the separation, a coarser ground PAC type was compared to a standard PAC type with regard to elimination results of OMP as well as separation performance. With a PAC dosing rate of 20 mg/l an average of 64.7 wt% of the standard PAC and 79.5 wt% of the coarse-ground PAC could be separated in the hydrocyclone classifier. A total average separation efficiency of 93-97 wt% could be reached with a combination of both hydrocyclone classifier and cloth filter. Nonetheless, the OMP elimination of the coarse-ground PAC was not sufficient enough to compete with the standard PAC. Further research and development is necessary to find applicable coarse-grained PAC types with adequate OMP elimination capabilities.

Reversible and Species-Specific Depigmentation Effects of AZD3293, a BACE Inhibitor for the Treatment of Alzheimer's Disease, Are Related to BACE2 Inhibition and Confined to Epidermis and Hair.

BACKGROUND: AZD3293 (also known as LY3314814) is a novel, potent, non-selective BACE1/BACE2 inhibitor currently in Phase 3 clinical development for the treatment of Alzheimer's disease. OBJECTIVES: The purpose of these studies was to characterize the effects, putative mechanism, and reversibility of hypopigmentation following treatment with AZD3293 in pigmented Long-Evans rats, Beagle dogs, human cell cultures, and humans. DESIGN: Nonclinical studies were conducted in Long-Evans pigmented rats, and both young and older Beagle dogs using a variety of oral dose levels of AZD3293 or AZD3839 (BACE inhibition reference compound; used in older dogs only) for dosing durations of 13 to 26 weeks. In vitro studies of normal human epidermal melanocytes and reconstituted human epidermis were also conducted. Skin biopsy data from a multiple-dose Phase 1 clinical study of AZD3293 (NCT01795339) are also reported. SETTING: Nonclinical in vivo and in vitro studies were conducted in laboratory settings in the US, Canada, and France; the multiple dose clinical study was conducted in a specialized inpatient setting in the US. PARTICIPANTS: Beagle dogs: 13-week study N=36 young (8-10 mo) animals; 39-week study N=64 young animals; and a second 13-week study N=32 older (30-32 mo) animals. Long-Evans rats: N=68 animals. Multiple-dose clinical study: only data for subjects enrolled in Part 2 of this study are included in this report (N=16). INTERVENTIONS: AZD3293 was the primary intervention used in these studies. AZD3839, a relatively BACE1-selective reference inhibitor compound was used in one group in the 13 week study in older Beagle dogs and one in vitro assessment. Finally, AZ1340, another relatively BACE1-selective reference inhibitor compound was used only in one in vitro assessment. MEASUREMENTS: Measurements for the nonclinical studies in dogs and rats included macroscopic observation and assessment of skin biopsies via histopathology, immunochemistry, and electron microscopy. Measurements for the in vitro studies included melanocyte premelanosome protein (PMEL) processing, cytotoxicity, melanin synthesis, Pmel17 labeling, and melanocyte dendricity. Measurements in the clinical study included scoring of melanin content in skin biopsies taken before and after dosing with AZD3293 over 14 days at dose levels up to 150 mg. RESULTS: Depigmentation in rats and dogs was limited to skin, hair, and mucosa with no effects on other pigmented tissues. At a cellular level depigmentation was observed within a week of treatment, whereas the appearance of depigmentation in skin and hair did not become apparent until, at earliest, 4 weeks of treatment. The depigmentation effects were reversible, not associated with degenerative or inflammatory changes, and were dose- and species-dependent in severity. Full recovery of melanization was observed at the microscopic (cellular) level and at least partial recovery was seen in the macroscopic appearance of animals by the end of the 12-week recovery period in both rats and dogs. Interestingly, no changes in melanin production or melanocyte morphology were seen in human primary melanocytes or reconstituted human epidermis in vitro. Finally, there were no changes in melanization level in skin biopsies following 12 days of daily AZD3293 treatment at doses of AZD3293 up to 150 mg/day in human subjects. CONCLUSIONS: AZD3293, a novel, potent, non-selective BACE1/BACE2 inhibitor is in development as a potentially disease-modifying treatment for Alzheimer's disease. Chronic nonclinical studies in Beagle dogs and pigmented rats showed macroscopic and microscopic hypopigmentation effects of AZD3293 that were limited to skin, hair, and mucosa. These effects were shown to be reversible in both species. Analysis of data from nonclinical and in vitro studies suggests that hypopigmentation is caused by BACE2 inhibition resulting in accumulation of a premelanosome protein fragment, which interrupts the normal production of melanin. No macroscopic or microscopic reports of hypopigmentation were observed in a Phase 1 clinical study following 13 doses of AZD3293 over 14 days at dose levels up to 150 mg/day. These data suggest that hypopigmentation is species-specific and humans appear to be least sensitive to the depigmentation effect caused by BACE2 inhibition.

Changes in hoof health and animal hygiene in a dairy herd after covering concrete slatted floor with slatted rubber mats: a case study.

The objective was to investigate the effect of changing the flooring in the alleys of a barn from slatted concrete to slatted rubber mats on hoof disorders and animal hygiene in 44 loose-housed Brown Swiss dairy cows. Cows were examined for disorders of the hind hooves (hemorrhages, white line fissures, ulcers, heel horn erosion, and digital dermatitis) and for skin lesions. The dirtiness of the animals and of the floor was recorded. Climatic (temperature, humidity) and ammonia gas conditions were measured. Evaluations were carried out when the cows were housed on a concrete slatted floor and after 4 and 10 mo on soft flooring (slatted rubber mats, 29-mm thick). The anatomical portion of claw (medial, lateral), number of lactations (parity), and days in milk were included as covariates in the statistical model. Changing the flooring from slatted concrete to slatted rubber mats increased the score for white line fissures [1.0 ± 0.3 (concrete) vs. 2.5 ± 0.4 (10 mo rubber mats)] and influenced air humidity (i.e., the difference in the absolute humidity between the inside and outside of the barn increased from 1.5 ± 0.1 to 1.7 ± 0.2g/m(3)), whereas the other hoof disorders, skin lesions (score of 8.7 ± 0.3), the dirtiness of the animals (score of 5.9 ± 0.3), and the floor (score of 2.1 ± 0.1), and ammonia gas concentration (2.6 ± 0.3mg/kg) were not affected (overall scores or measures; mean ± SE). Lateral claws were more affected (except for heel horn erosion) than medial claws (estimated effects between 1.3 ± 0.2 and 3.0 ± 0.6). Parity influenced hoof disorders (except for hemorrhages) and skin lesions (estimated effects between -0.6 ± 0.3 and 0.5 ± 0.2). Days in milk influenced hoof disorders, but had no effect on skin lesions and on the dirtiness of the animal. Irrespective of floor type, the slots (2.6 ± 0.1) were dirtier than the slats (1.6 ± 0.1). In conclusion, covering slatted concrete flooring with slatted rubber mats partially impaired hoof health but did not influence skin lesions or the dirtiness of the cows or the floor. Similar results were found for climatic conditions, as ammonia gas concentration was not affected, but absolute humidity increased in the barn when rubber mats were present.

What happens with cow behavior when replacing concrete slatted floor by rubber coating: a case study.

An enhanced productive life cycle and improved animal welfare are aims pursued in dairy husbandry. This study assesses experimental observations on floor-associated behavior during the stepwise replacement of concrete slatted flooring by rubber mats. For this purpose, estrus (mounting) and hygiene behavior (licking while standing on 3 legs and caudal licking) within a herd of 50 loose-housed Brown Swiss dairy cows were analyzed by video observation before and after floor reconstruction. Still photographs and pedometers were used to asses step length and number of steps, representing walking behavior. Compared with the concrete floor surface, rubber coating led to an increase in step length (58 +/- 1 vs. 70 +/- 1 cm; n = 35) and in steps per day (4,226 +/- 450 vs. 5,611 +/- 495; mean +/- SEM; n = 9). Mounting was higher on the flooring covered with rubber mats (23 vs. 112). Collapsing or slipping during mounting only occurred on concrete slatted flooring (in 19 out of 23 mounting actions). Licking while standing on 3 legs and caudal licking increased up to 4-fold (105 vs. 511 observations). In conclusion, improvements were found in behavior when rubber-coated slatted floor surfaces were used in dairy cattle housing in transition from concrete flooring. Disorders in estrus and hygiene behavior were associated with the flooring of the barn and were relatively easy to investigate within the framework of farm welfare assessments.

Histopathologic and immunophenotypic characterization of extramedullary plasmacytomas in nine cats.

To contribute to the existing body of knowledge in the literature on the apparently rare extramedullary plasmacytoma in cats, lymphoid tumors with plasmacytic cellular morphology taken from nine cats were examined. The paraffin-embedded material was investigated by standard hematoxylin and eosin, and special staining techniques (Giemsa, Congo-red, and periodic acid-Schiff reaction). The tumors also were examined immunohistochemically for the presence of immunoglobulin G, immunoglobulin A, immunoglobulin M, immunoglobulin light chains (lambda, kappa), various amyloid proteins, and FeLV-antigen (p27 protein). An immunoglobulin-producing tumor of plasmacellular origin (extramedullary plasmacytoma [EMP]) could be diagnosed in all cases on the basis of immunohistochemical light-chain expression. All but one of the neoplasms occurred in the skin of older, predominantly male cats. As in humans and dogs, the following types could be identified according to their morphologic features: mature type (two), cleaved type (two), asynchronous type (four), and polymorphous type (one). The tumor tissue of three cats revealed amyloid deposits, which were immunohistochemically diagnosed as ALlambda-amyloid in all three cases.

Health effects of sulfur-related environmental air pollution. I. Executive summary.

The motivation of simulating real-world environmental exposure in a number of long-term studies with dogs was to address the question of whether or not perpetual inhalation of air pollutants can initiate diseases in healthy lungs and can thus contribute to the increasing prevalence of respiratory diseases in industrialized countries. The major conclusion of this article is that this question has to be answered in the negative for the simultaneous inhalation of the major constituents of combustion-related air pollution, particle-associated sulfur(IV), and particle-associated hydrogen ions. Over 13 mo, 8 healthy beagle dogs were exposed in 2 whole-body chambers daily for 16.5 h to 1 microm neutral sulfite [sulfur(IV)] particles at a mass concentration of 1.5 mg m-3 and for 6 h to 1.1 microm acidic sulfate particles carrying 15 micromol m-3 hydrogen ions into the canine lungs. This longitudinal study was characterized by repeated observations of individual respiratory response patterns. To establish baseline data the dogs were repeatedly examined preexposure while the chambers were ventilated over 16 mo with clean air. Each individual served thus as its own control. Another eight dogs served as additional controls. They were housed in 2 chambers ventilated with clean air over the entire study period of 29 mo. To assess response patterns, respiratory lung function tests were performed pre- and postexposure, segmental lung lavages were repeatedly performed to obtain epithelial lining fluid from the lungs for analysis of cell content, cell function, and biochemical indicators of lung injury, and radiolabeled test particles were used to study pathways of intrapulmonary particle elimination. At the end of the study, the lungs of all animals were morphologically and morphometrically examined. Functional and structural responses were finally compared to those observed previously as a result of a sole exposure of canine lungs to neutral sulfite particles over 10 mo (Heyder et al., 1992). Interactions between responses induced by neutral sulfite and acidic sulfate particles occurred, but antagonism rather than synergism was observed. The responses induced by sulfur(IV) were less pronounced, not detectable, or even reversed when hydrogen ions were also delivered to the lungs. On the other hand, responses not induced by the sole exposure to sulfur(IV) were observed: The activity of alkaline phosphatase was elevated and type II pneumocytes proliferated. It can, however, be concluded that long-term exposure of healthy lungs to particle-associated neutral sulfur(IV) and hydrogen ions at concentration close to ambient levels causes subtle respiratory responses but does not initiate pathological processes in the lungs. In other words, the perpetual inhalation of sulfur(IV) and hydrogen ions from the atmospheric environment presents no health risk to the healthy lungs. It is thus also very unlikely that respiratory diseases can be initiated by the inhalation of these pollutants.

Conformational difference between nuclear and cytoplasmic actin as detected by a monoclonal antibody.

Using a reconstituted complex of profilin and skeletal muscle actin as an antigen, we generated a monoclonal mouse antibody against actin, termed 2G2. As revealed by immunoblots of proteolytic actin fragments and by pepscan analysis, the antibody recognises a nonsequential epitope on actin which is located within three different regions of the sequence, consisting of aa131-139, aa155-169, and aa176-187. In the actin model derived from X-ray diffraction, these sequences lie spatially close together in the region of the nucleotide-binding cleft, but do not form a coherent patch. In immunoblots, 2G2 reacts with all SDS-denatured actin isoforms and with actins of many vertebrates. In contrast, its immunofluorescence reactivity is highly selective and fixation-dependent. In fibroblasts and myogenic cells, fixed and extracted by formaldehyde/detergent, stress fibres or myofibrils, respectively, remained unstained. Likewise, after microinjection into living cells, 2G2 did not bind to such microfilament bundles. Extraction of myosin and tropomyosin did not alter this pattern indicating that the lack in reactivity is probably not due to epitope-masking by actin-binding proteins. More likely, the reason for the lack of reactivity with filamentous actin is that its epitope is not accessible in F-actin. However, the antibody revealed a distinct pattern of nuclear dots in differentiated myogenic cells but not in myoblasts, and of fibrillar structures in nuclei of Xenopus oocytes. In contrast, after methanol treatment, a 2G2-specific staining of stress fibres and myofibrils was observed, but no nuclear dot staining. We conclude that 2G2, in addition to binding to SDS- and methanol-denatured actin, recognises a specific conformation of native actin which is present in the nucleus and specified by compaction of the antibody-reactive region into a coherent patch. This conformation is apparently present in differentiated myogenic cells and oocytes, but not in cytoplasmic actin filament bundles.

Prognostic value of histopathological grading in canine extramedullary plasmacytomas.

The canine extramedullary plasmacytoma (cEMP) has recently been the subject of numerous investigations, indicating that the histomorphologic diagnosis is often difficult because of the variety of morphologic features. Therefore, the objective of this study was to establish a subclassification scheme for cEMPs and to evaluate correlations between the types and malignancy. Retrospectively, 117 cEMPs, all immunohistochemically characterized by a monoclonal immunoglobulin light-chain expression, were collected and assigned to morphologic types. These types were compared using data from a follow-up study on metastasis and tumor recurrence, then compared by proliferation rate, determined by immunohistochemical detection of the antigen Ki-67. Histopathologic typing revealed five different types of cEMPs, ranging from the mature type with typical plasma cells to the polymorphous-blastic type. Between these two forms, three additional types were established: hyaline, cleaved, and asynchronous. Most of the cEMPs were of the cleaved and asynchronous types. In all cEMPs, mononuclear and multinuclear giant cells were present to varying degrees. Although the results of cell proliferation and the follow-up study indicated less benign behavior by the polymorphous-blastic type, the proliferation rate revealed no statistically significant differences among the cEMP types. The clinical data therefore confirmed previous findings that the risk of tumor recurrence and metastasis in general can be classed as low. The established cEMP typing system is probably a very helpful diagnostic tool, although the types cannot be used for a tumor grading system.

[The impact of suboptimal animal husbandry practices on animal health and economic profitability using the example of tie-in and loose housing system of dairy cattle]. / Auswirkung von Haltungsmängeln auf Tiergesundheit und Wirtschaftlichkeit am Beispiel der Anbinde- und Laufstallhaltung von Milchkühen.

In this study of two common housing systems of dairy cattle, the tie-in system and the loose housing system, check lists were created to evaluate whether these husbandry systems fulfill the needs of the animals. Furthermore, a combination of questionnaires and interviews were employed to assess the qualification of dairy stockmen to handle the animals. These checklists should provide a useful tool for those persons involved in the examination of husbandry systems, both by providing a written record and by providing a clear outline of all the points that need to be covered during such an examination. The study, done in the way of an explorative analysis of data, included 22 farms (14 with tie-in systems and 8 with loose housing systems) and a total of 802 animals. With regard to the economic effects of poor management and housing conditions, several interesting and statistically noteworthy correlations emerged. TIE-IN SYSTEM: Positive correlations were found between severity of behavioural abnormalities (behave)and number of injuries due to husbandry system (injury); injury and number of inseminations per pregnancy (preg); injury and age of cow (age); preg and cell count of milk (cell). Negative correlations were found between cell and milk yield (milk) as well as between the qualification of stockmen (equal) and inappropriate technical design of the housing environment (tech). LOOSE HOUSING SYSTEM: Positive correlations existed between behave and injury, and between tech and injury. Negative correlations were found between milk and cell, equal and tech, and milk and age. The magnitudes of these correlations were quantified by means of linear regression analysis. Comparison of the two husbandry systems revealed that while the loose housing systems is associated with significantly more problems related to tech, it is associated with significantly fewer problems related to injury. It seems that in this housing system cows are better able to avoid injury since they are allowed to move freely. No significant differences in behavior were found between the two husbandry systems. The present study shows the importance of proper technical design of housing environments, both in relation to animal welfare and to economic profitability.

[Effect of steam application based on microbiological and parasitologic test procedures]. / Untersuchungen zum Effekt der Dampfeinwirkung anhand mikrobiologischer und parasitologischer Prüfverfahren.

In the present study steam application was investigated with regard to microbicidal and parasiticidal effects. The cleaning apparatus used (Uninova Company) works at a boiler pressure of about 5 bar and consequently with a temperature up to 155 degrees C inside the boiler. Whereas the ambient atmosphere working temperature of steam is slightly below 100 degrees C. The tests are based on the DVG guidelines for testing chemical disinfectants (2). Different steaming times and distances were used in germ carrier tests with three different germ carriers (tile, wood, carpet) and three different test germs (Staphyloccocus aureus, Pseudomonas aeruginosa, Candida albicans) in order to determine the optimum conditions for biocidal effects of steam-application. These optimum conditions were additionally tested with two test viruses (ECBO- and Reo-virus) and a parasitological resting form (ascarid worm eggs). Swirling of germs caused by steam turbulence was minimized by covering the steam outlet nozzle with cloth. The experiments showed logarithmical reduction factors of at least 5.0 in the germ count at steaming times of 5 seconds and a steaming distance of 2.5 cm for all three test germs on all three germ carriers (mean of 10 repeated tests). The virological tests showed good disinfection results after a steaming time of only 2 seconds using aseptic gauze as germ carrier and also after 5 seconds using wood as a carrier. Finally in testing vitality of undeveloped Ascarid worm eggs only 2 seconds of steam treatment proved to be sufficient for a 100 percent destruction. According to the present results steam treatment is most likely to become a valuable, ecologically compatible method in controlling hygienic problems, with a potential of partly replacing chemical disinfectants. In particular we see applications in keeping pets and companion animals, provided the above mentioned rules are followed (steaming distance 2.5 cm; steaming time 5 seconds; cloth). In farm animal stables steam disinfection seems harder to achieve because of large, rough surfaces and economical reasons as e.g. expenditure of time and energy.

Identification of lambda light chain amyloid in eight canine and two feline extramedullary plasmacytomas.

Amyloid deposition in varying amounts and with variable patterns of distribution (focal or diffuse) was demonstrated in eight canine and two feline extramedullary plasmacytomas expressing lambda light chains. Frequently, the neoplastic plasma cells had been displaced by the amyloid deposits. Foreign-body giant cells were regularly detected in the vicinity of the amyloid. In all 10 cases, Congo-red staining of the amyloid was resistant to potassium permanganate oxidation. Immunohistochemically, the amyloid reacted positively with cross-reacting antibodies against human and equine A lambda amyloids. Extramedullary plasmacytomas accompanied by localized AL amyloidosis have so far been described in human beings, dogs, cats and horses.

[Burden of fattening pigs and the environment of the pig fattening farms caused by lung-passing dust particles, pig stall specific bacteria and ammonia]. / Untersuchungen zur Belastung von Mastschweinen sowie der Umgebung von Mastschweineställen durch atembaren Feinstaub, stallspezifische Bakterien und Ammoniak.

According for their topographic and isolated locations (no built-up area or trees down-wind) 13 fattening pig pens with an average stocking rate of 737 (360-2500) have been investigated for burden by immission of animals and the environment outside the stables up to a distance of 100m downwind of the source. These studies have been carried out between June 1988 and April 1989 in monthly intervals. The investigated parameters have been: dust of particle size < 5 microns, stable specific bacteria, ammonia and symptoms of animals respiratory diseases. In the stalls could be shown an significant seasonal influence on bacteria, lung passing dust content and ammonia concentration with a maximum during December/January (1.1 x 10(6) CFU/m3; 0.26 mg/m3; 27 ppm) and minimum during June/July (5.7 x 10(5) CFU/m3; 0.075 mg/m3; 11 ppm). In the environment outside the pigsties a significant seasonal influence could be found only for the stable specific bacteria up to the distance of 100m of the source of emission, showing a maximum during fall and winter (1.7 x 10(3) CFU/m3) and minimal concentration during spring and summer (9.3 x 10(2) CFU/m3). Due to emission of spent air a high significant reduction of the stable specific bacteria and lung passing dust concentration could be established outside the stables within a distance of 10 m. The content of stable specific bacteria come to 0.2% (1941 CFU/m3) compared with the amount measured at the air outlet of the spent air shaft. At this distance the lung passing dust concentration has been reduced to 11% (0.016 mg/m3) of the concentration at the emission source. In comparison to the examined "neutral air" upwind, the content of lung passing dust downwind has not been heightened significantly at any measuring point or time of the year, whereas the content of stable specific bacteria downwind was significantly higher up to a distance of 50 m (p < or = 0.01). The stable specific bacteria that were isolated from the air outside the pigsties, mostly gram positive cocci, had in part a strong resistance against Erythromycin, Penicillin, Tetracyclin and Ampicillin. The fact that in all investigated farms irritations or diseases of the animals respiratory tract in different degrees of intensity could be determined shows the urgency to minimize the burden by optimizing the hygienic situation inside the stalls. This means especially the colder period of the year, because a high frequency of transgression of the ammonia threshold value according to German regulations for pig housing could be found in this time.

Immunoglobulin-producing tumours in dogs and cats.

Tumours with a plasmacytoid pattern taken from 32 dogs and four cats were examined for the presence of immunoglobulins, which would allow them to be designated as B-cell lymphomas. Within a total of 19 immunoglobulin-positive tumours, three types could be distinguished: extramedullary plasmacytoma (15), multiple myeloma (two) and immunocytoma (two). These tumours occurred in 18 of the dogs, and in one cat (extramedullary plasmacytoma). The characteristics of the immunoglobulin-producing tumours were investigated by light and electron-microscopy as well as by immunohistochemical methods. Seventeen of the 19 tumours expressed lambda-type light chains and one tumour kappa-type light chains. Heavy chains were also synthesized by five tumours.

[Memory training in old age: theoretical background and development of an intervention program for nursing home residents]. / Gedächtnistraining im Alter: Theoretischer Hintergrund und Entwicklung eines Interventionsprogramms für Altenheimbewohner.

A survey of the literature reveals that studies providing hard evidence of the effects of training on improvement of cognitive skills in old age focus on highly specialized training measures. To date there are hardly any suitable procedures for memory training that have a broad effect on the consciousness of impaired individuals which would nurture a different attitude towards the entire complex of learning and memory. For this reason a memory training program was developed, aimed at conserving, reactivating, and fostering the cognitive skills of non-demented residents of old people's homes. The training program, carried out over a 3-month period, consists of a total of 24, 45-min training units. The first half of the memory training program prompts participants to use as many channels of perception as possible, and thereby, also to employ compensation possibilities. In addition, there are exercises for improving observation and concentration and for understanding the functions of memory on the basis of a simplified model of information processing. The second half of the memory training program focuses on exercises to improve short-term and medium-range retention. The exercises are oriented in content to the daily situations relevant to the residents in which memory performance is expected. The memory training program was used for the first time in a geriatric facility in Mannheim, FRG. Continued use of the program, coupled with an evaluation, is planned as part of a research project in several homes for the elderly in that greater metropolitan area.

[Detection of dementia and depression using the Brief Assessment Interview (BAI): results of a reliability and validity study with residents of a nursing home in Mannheim]. / Die Erfassung von Demenz und Depression mit Hilfe des Brief-Assessment-Interviews (BAI): Ergebnisse einer Reliabilitäts- und Validitätsstudie bei Altenheimbewohnern in Mannheim.

Described here is the German version of the Brief Assessment Interview (BAI), an instrument developed originally in the course of the US-UK cross-national studies and designed to compile data on dementia and depression among the elderly. A study in Mannheim, FRG, of residents in an old people's home tested the reliability and validity of the BAI. Raters corresponded to a high degree on both the dementia and depression scales; intraclass coefficients (ICC) amounted to 0.95 and 0.97, respectively. Compared to the interrater reliability, test-retest reliability was somewhat lower (dementia scale: 0.83, depression scale; 0.74), but always significant at the 1% level. The internal consistency of the dementia scale lay between 0.62 and 0.77, and that of the depression scale between 0.78 and 0.92. In evaluating the validity of BAI, results of the dementia and depression scales were compared to the corresponding diagnoses. These independent diagnoses had been made with the aid of the Feighner criteria by the director of the facility, who had special training in psychiatry. The diagnoses yielded a significant relationship (p less than 0.01) between the dementia (r = 0.49) and depression scales (r = 0.60). The BAI also attained sufficiently high values for sensitivity, specificity, and total efficiency. It is, therefore, well suited for use in elderly target groups that are otherwise difficult to assess, and it also affords a high degree of international comparability.

[Studies on survival of salmonellae on agricultural areas (author's transl)]. / Modellversuche zur Persistenz von Salmonellen auf landwirtschaftlichen Nutzflächen.

Subsequent to experimental contamination of grass plots, the persistence of Salmonella typhimurium has been investigated under outdoor climatic conditions. The studies showed the following results: -in the usually shaded zones of the blade of grass near the subsoil and in the superficial soil layer itself, the Salmonella could be reisolated over a period of 28-77 days by Salmonella enrichment methods. On the other hand, the indicator bacteria could be reisolated from the apical zone of the blade of grass for only a maximum of 5 days by the same microbiological methods. In general however, regular isolations of Salmonellae were possible for only a third part of the maximal survival time, which could be detected in the actual experiments. -longer periods of sunshine in connection with only few rainfall seemed to reduce the survival times of the indicator bacteria. The results lead to the conclusion, that an interval of 6 weeks between spreading of liquid manure and the first drive to pasture will result in decreased risk of bacterial infection for grazing animals.

[Studies on survival of Salmonella typhimurium in different types of soils under outdoor climatic conditions (author's transl)]. / Experimentelle Untersuchungen zur Persistenz von Salmonella typhimurium in verschiedenen Kulturböden.

Subsequent to experimental contamination of the surface of different soils--sand, loam and clay types--persistence of S. typhimurium had been investigated under outdoor climatic conditions over the period June 1977 to Dec. 1978 to judge public health problems resulting from land application of animal manures. The studies showed the following results:--in general survival time of Salmonellae reduced with decreasing temperature both at the soil surface and in deeper soil layers of the correspondent soil-type. Relative to average soil temperatures of 14.1, 3.2 and -0.6 degrees C the Salmonellae showed average survival times of 46.8 d, 32.1 d and 3.3 d respectively (p < 0.01).--by means of infiltration Salmonellae penetrated into the soils. Below soil surface the pathogens exhibited mean survival times approximative twice as long as pathogens remaining at the soil surface. At the soil surface the Salmonellae persisted over an average period of 26 d (3-69 d as a function of soil type), while out of deeper soil layers the pathogens could be reisolated over an average period of 44.7 d (7- > 120 d as a function of soil type), (p < 0.05).--with increasing depth of soil (5-50 cm) frequency of isolation of Salmonellae reduced (p < 0.01). In this connection rate of infiltration seemed to be restricted mostly within the first 15 cm.--the heavier soil types gave better chances for survival of S. typhimurium than the sandy soil types (p < 0.01). This could be shown by the higher isolation rate of Salmonellae from the loam- and clay-type soils (15.9%), compared with the isolation rate of 7.8% from the sandy soil-types.--genuine soil microorgnisms took part in elimination of Salmonellae. The degree of self-decontamination however was not related to the biomass contents of the investigated soils. From the viewpoint of environmental hygiene, the results point to distinct organic loading capacities of soils. This leads to the conclusion that the degree of manuring should be devoted to the capability of self-decontamination of the corresponding soil-type. Relative to heavier soils, this results in longer intervalls of manuring. Related to the spreading of liquid manures, methods have been developed to avoid odor emission by injecting the liquid manures into the soil. These methods seem to be critical from the viewpoint of hygiene, because beneath soil surface pathogenic bacteria, as it could be shown, exhibited survival times for much longer periods than at the surface of the soils. The presented data point to the urgency of decontaminative pretreatments of animal manures (esp. to regions with high density of livestock) before spreading on land.