Impact of Covid-19 on farming systems in Europe through the lens of resilience thinking.

Context: Resilience is the ability to deal with shocks and stresses, including the unknown and previously unimaginable, such as the Covid-19 crisis. Objective: This paper assesses (i) how different farming systems were exposed to the crisis, (ii) which resilience capacities were revealed and (iii) how resilience was enabled or constrained by the farming systems' social and institutional environment. Methods: The 11 farming systems included have been analysed since 2017. This allows a comparison of pre-Covid-19 findings and the Covid-19 crisis. Pre-Covid findings are from the SURE-Farm systematic sustainability and resilience assessment. For Covid-19 a special data collection was carried out during the early stage of lockdowns. Results and conclusions: Our case studies found limited impact of Covid-19 on the production and delivery of food and other agricultural products. This was due to either little exposure or the agile activation of robustness capacities of the farming systems in combination with an enabling institutional environment. Revealed capacities were mainly based on already existing connectedness among farmers and more broadly in value chains. Across cases, the experience of the crisis triggered reflexivity about the operation of the farming systems. Recurring topics were the need for shorter chains, more fairness towards farmers, and less dependence on migrant workers. However, actors in the farming systems and the enabling environment generally focused on the immediate issues and gave little real consideration to long-term implications and challenges. Hence, adaptive or transformative capacities were much less on display than coping capacities. The comparison with pre-Covid findings mostly showed similarities. If challenges, such as shortage of labour, already loomed before, they persisted during the crisis. Furthermore, the eminent role of resilience attributes was confirmed. In cases with high connectedness and diversity we found that these system characteristics contributed significantly to dealing with the crisis. Also the focus on coping capacities was already visible before the crisis. We are not sure yet whether the focus on short-term robustness just reflects the higher visibility and urgency of shocks compared to slow processes that undermine or threaten important system functions, or whether they betray an imbalance in resilience capacities at the expense of adaptability and transformability. Significance: Our analysis indicates that if transformations are required, e.g. to respond to concerns about transnational value chains and future pandemics from zoonosis, the transformative capacity of many farming systems needs to be actively enhanced through an enabling environment.

Local variations of the chemistry in as-cast gamma-TiAl (TiBx) alloys and its consequence for thermomechanical treatments

The first part of the paper presents an accompanying investigation to a thermomechanical processing route of gamma-TiAl turbine blades. By means of scanning electron microscopy and energy dispersive X-ray (EDX) analysis, the chemical homogeneity and the microstructures of gamma-TiAl as-cast ingots, work pieces and the final turbine blades are determined. We find that the local Al-content in as-cast ingots can vary by more than 1.5 at.%. Large chemical inhomogeneities present in as-cast ingots can only be eliminated to a certain degree by subsequent thermomechanical processing. An additional aim of the study is to assess the influence of a thermomechanical processing on the morphology of titanium boride precipitates and the alpha2-Ti3Al-phase. The second part of the paper contains a detailed analytical study devoted to homogenization of a range of gamma-TiAl cast alloys. Different microstructures are generated in a laboratory-scale argon-arc furnace by both rapid and slow solidification rates and an additional homogenization treatment, respectively. Quantitative EDX analysis shows that only rapid solidification of ingots with a subsequent homogenization treatment leads to a nearly chemically homogeneous microstructure.

Opportunities for improving managed care for individuals with dementia: Part 1--The issues.

In this first part of a two-part article, we review the prevalence of, costs associated with, and treatments for Alzheimer's disease and related dementias, a leading cause of disability in the elderly. New, innovative, and costly drugs to combat dementia are being introduced, causing pharmacy costs to rise. These new drugs, however, may reduce overall medical costs and improve the quality of life of patients with dementia and their caregivers. Issues of cost, excessive service utilization, and quality of life will have significant impact on managed care organizations in the near future as the rapidly aging population experiences significant disability and illness related to dementia. In the second part of this article, we describe the framework for a disease management program for patients with dementia, similar to programs in existence for diabetes and other chronic diseases, that could enable managed care organizations to effectively care for these patients.

Opportunities for improving managed care for individuals with dementia: Part 2--A framework for care.

In this second part of a review of dementia, we argue that managed care organizations must develop strategies to identify and manage patients with dementia, whose numbers will increase dramatically in the near future. Improved coding and use of validated self-report instruments that include caregivers as information sources could assist in identifying patients with dementia who could benefit from disease management programs. These programs should include population-based screening efforts; the development of practice guidelines; the use of case managers; education of caregivers, case managers, and physicians in issues such as availability of community services, patient/caregiver self-management techniques, and the latest developments in efficacious treatment; and monitoring of care through quality assurance activities. Dementia is a highly prevalent, devastating, and costly chronic illness of the elderly, but it is also eminently manageable. Managed care has the potential to improve the quality of life and care for these patients, while managing the costs.

Identification of the border between fibronectin type III homologous repeats 2 and 3 of the neural cell adhesion molecule L1 as a neurite outgrowth promoting and signal transducing domain.

To determine the domains of the neural cell adhesion molecule L1 involved in neurite outgrowth, we have generated monoclonal antibodies against L1 and investigated their effects on neurite outgrowth of small cerebellar neurons in culture. When the 10 antibodies were coated as substrate, only antibody 557.B6, which recognizes an epitope represented by a synthetic peptide comprising amino acids 818 to 832 at the border between the fibronectin type III homologous repeats 2 and 3, was as efficacious as L1 in promoting neurite outgrowth, increasing intracellular levels of Ca2+, and stimulating the turnover of inositol phosphates. These findings suggest that neurite outgrowth and changes in these second messengers are correlated. Such a correlation was confirmed by the ability of Ca2+ channel antagonists and pertussis toxin to inhibit neurite outgrowth on L1 and antibody 557.B6. These observations indicate for the first time a distinct site on cell surface-bound L1 as a prominent signal-transducing domain through which the recognition events appear to be funneled to trigger neurite outgrowth, increase turnover of inositol phosphates, and elevate intracellular levels of Ca2+.

Several extracellular domains of the neural cell adhesion molecule L1 are involved in homophilic interactions.

The neural cell adhesion molecule L1 is a multidomain protein that plays important roles in cell adhesion, migration, and neurite outgrowth. It can interact with itself by a self-binding, i.e., homophilic adhesion mechanism (Kadmon et al.: J Cell Biol 110: 193-208, 1990a). To determine the domains of L1 involved in homophilic binding, we have generated protein fragments of L1 in a prokaryotic and a eukaryotic expression system and used these covalently coupled to fluorescent microspheres to quantify aggregation between them by cytofluorometric analysis. Protein fragments containing the first and second Ig-like domains and the third fibronectin type III homologous repeat showed avid self-binding. Ig-like domains III and IV also showed some self-binding, whereas Ig-like domains V and VI and fibronectin type III homologous repeats 1 and 2 as well as 4 and 5 were less or not active. Binding between different domains was also observed: fibronectin type III homologous repeats 4 and 5 interacted with Ig-like domains I and II, and fibronectin type III homologous repeats 3-5 interacted with all Ig-like domains. These results were confirmed by experiments testing the binding of fragment-conjugated microspheres to substrate-coated L1 or to cell surface-expressed L1 on cultured neurons. Binding of L1 to itself was interfered with by all protein fragments tested, suggesting that also less avidly binding domains of L1 contribute to homophilic binding. These observations indicate prominent functional roles of both Ig-like domains and fibronectin type III homologous repeats in homophilic binding of L1.

Several extracellular domains of the neural cell adhesion molecule L1 are involved in neurite outgrowth and cell body adhesion.

The neural cell adhesion molecule L1 is a multidomain protein that plays important roles in cell adhesion, migration, and neurite outgrowth. To analyze structure-function relationships of L1 in neurite outgrowth and cell body adhesion, we have expressed and purified a set of different fragments of the extracellular part of this glycoprotein in CHO cells and in Escherichia coli. When neurite outgrowth from small cerebellar neurons was measured on substrate-coated L1 or L1 fragments, neurite outgrowth was promoted by the immunoglobulin-like domains I-II, III-IV, and V-VI, and by the fibronectin type III homologous repeats 1-2, while the fibronectin type III homologous repeats 3-5 were ineffective. In contrast, cell bodies of small cerebellar neurons adhered mostly to the immunoglobulin-like domains I-II and V-VI, and to the fibronectin type III homologous repeats 3-5, but less to the immunoglobulin-like domains III-IV and fibronectin type III homologous repeats 1-2. In both assays, the neuronal cell surface receptor for all active protein fragments was identified as L1. No significant differences in functional activities were found between fragments with and without carbohydrate structures. These findings indicate that L1 uses several domains for homophilic interactions overlapping for the two functions analyzed here, but also showing some regional specialization. Furthermore, we show that a homophilic molecule uses several domains in one function, with neurite outgrowth requiring more domains than adhesion for maximal activity.

Production and secretion in CHO cells of the extracellular domain of AMOG/beta 2, a type-II membrane protein.

A hybrid gene consisting of the sequences coding for the signal peptide and N terminus of a type-I membrane protein, the neural cell adhesion molecule (N-CAM), and the extracellular domain of the adhesion molecule on glia (AMOG/beta 2), a type-II membrane protein, was constructed. The sequence was inserted into a eukaryotic expression vector containing the human cytomegalovirus promoter and the glutamine synthetase selection marker, and used to transfect Chinese hamster ovary cells. The resulting stably transformed cell lines produced large amounts of soluble recombinant AMOG/beta 2 (reAMOG/beta 2), which was secreted into the culture medium as a heavily glycosylated 40-55-kDa protein. N-terminal sequence analysis revealed that the protein is not cleaved at the natural signal peptide cleavage site of N-CAM, but two amino acids (aa) further downstream. Treatment of reAMOG/beta 2 with N-glycosidase F (GlycoF) reduced the molecular mass to 27 kDa, corresponding to the calculated mass of the unglycosylated form. In contrast to AMOG/beta 2 isolated from mouse brain, which is sensitive to endoglycosidase H, the immunoaffinity-purified re-protein is more resistant to this treatment, indicating that the sugars attached to reAMOG/beta 2 are mainly of the complex type. Our results demonstrate the feasibility of secreting the extracellular domain of a type-II membrane protein, which is usually inserted into the membrane with the C terminus facing the extracellular side.

A hydrophobic protein sequence can override a nuclear localization signal independently of protein context.

Simian virus 40 T antigen is specifically targeted to the nucleus by the signal Pro-Lys-Lys-128-Lys-Arg-Lys-Val. We have previously described the isolation of a simian virus 40 T-antigen mutant, 676FS, which retains a wild-type nuclear localization signal but fails to accumulate properly in the nucleus and interferes with the nuclear localization of heterologous proteins. Here we report that the hydrophobic carboxy-terminal sequence novel to 676FS T antigen overrides the nuclear localization signal if fused to other proteins, thereby anchoring the proteins in the cytoplasm. We discuss possible mechanisms by which missorting of such a fusion protein could interfere with the nuclear transport of heterologous proteins.

From quality assurance to quality improvement: the Joint Commission and the new quality paradigm.

Frank Appel, NAQAP's representative on the Joint Commission's QI Task Force, describes the ongoing Agenda for Change as progressively defining a new vision of effectiveness in healthcare organizations. This vision, first articulated in 1989 in the Principles of Organization and Management Effectiveness in Healthcare Organizations, is based on the fundamental concepts of total quality management (TQM), the new paradigm in healthcare. The first direct outcome of these principles is a new set of leadership standards that will appear in the 1992 Accreditation Manual for Hospitals (AMH). The Joint Commission is using the mechanism of standards' revision to lead healthcare organizations into a transition to continuous quality improvement (CQI). The 1992 AMH contains a revision of the current QA standards in the direction of quality assessment and improvement standards. The transition to CQI standards will be complete by 1994, when the data-driven process of CQI will also be incorporated into information management. Major CQI revisions also will occur in other parts of the management. Major CQI revisions also will occur in other parts of the AMH. "Second generation" clinical indicators presently under development reflect the process and cross-functional orientation of CQI. TQM is seen by the Joint Commission as the next step in a logical progression in QI methods, while CQI offers answers to the weaknesses of current QA programs. Mr. Appel concludes with an outline of these weaknesses, and a strong message of encouragement to the quality professional to meet the challenge of leadership during this transition.

Anticonvulsant serum levels are useful only if the physician appropriately uses them: an assessment of the impact of providing serum level data to physicians.

The ability to measure serum levels of anticonvulsants has been a significant advance in the treatment of epilepsy. This technique enables practitioners to monitor a patient's plasma concentration, to detect potential toxicity, and to assess compliance with the prescribed regimen. A retrospective study of 164 adults with epilepsy was conducted to evaluate how serum anticonvulsant determinations were used by physicians in their treatment of epilepsy. Results indicate that the availability of test results did not improve the degree of seizure control, nor did it diminish patient reports of toxicity. In 17% of therapeutic decisions, prescribers did not appear to use the blood levels appropriately in their therapeutic decision-making process. When physicians did appropriately utilize information from serum levels, the degree of seizure control improved significantly compared with when the prescribers did not use this information. The cost of determining serum levels of anticonvulsants is justified only if the information is appropriately utilized.

[The elimination of hydroxyethyl starch 200/0.5, dextran 40 and oxypolygelatine (author's transl)]. / Die Elimination von Hydroxyäthylstärke 200/0,5, Dextran 40 und Oxypolygelatine.

After withdrawal of 400 ml whole blood and subsequent infusion of 500 ml of a colloidal plasma substituent, the intravascular and renal colloid elimination was investigated in 40 test subjects. The individual colloidal solutions could no longer be demonstrated in the intravascular space after the following times: 10% hydroxyethyl starch 200/0.5 (anthrone method) after six weeks, 10% dextran 40 (anthrone method) after two weeks, 6% hydroxyethyl starch 200/0.5 (anthrone method) after four weeks and 5.5% oxypolygelatine (hydroxyproline method) after two days. Colloidal plasma substitutes are polydisperse solutions with various molecular weights and degree of hydroxyethylation and therefore, also have a large number of different elimination constants. With repeated application, the intravascular colloid concentration shifts in favour of the molecules with a longer half life which are difficult to eliminate. The elimination of the clinically employed dextran 40 and oxypolygelatine solution could be best described with an open two-compartment model. As a result of its greater heterogeneity, the elimination of the moderately high molecular weight hydroxyethyl starch 200/0.5 could only be characterized approximately even assuming three elimination constants. In the first four days, the hydroxyethyl starch 200/0.5 was more rapidly eliminated compared to dextran 40. However, subsequently a very much lower elimination from the intravascular space was found for about 3% of the administered hydroxyethyl starch 200/0.5. Oxypolygelatine was eliminated especially rapidly. Accordingly, the greatest renal clearance was found for oxypolygelatine, which showed a close relation to the molecular weight. On the other hand, a rapid elimination simultaneously is followed by a correspondingly lower volume effect.

Quality assurance in primary care: a strategy based on outcome assessment.

We describe an outcome-based approach to quality assurance in primary care and present data from an initial study made to explore its usefulness. A questionnaire, which asked patients to report on the status of their problem in terms of the amount of symptoms, activity limitation, and anxiety it caused, was mailed to adults who had been seen a month previously for upper respiratory tract infection, sore throat, or urinary tract infection. Outcome standards developed for these conditions indicated that patients should report no symptoms, activity limitation, or anxiety. Of the 127 patients who responded, 17% failed to meet these standards. A review of their medical records was conducted to test the value of using substandard problem-status outcome as an indicator of important deficiencies in care. Definite deficiencies in care were found for 57% of those with substandard outcomes and for 2% of those with acceptable outcomes. Corrective action was judged likely to benefit 95% of the cases with substandard outcome and 7% of those with acceptable outcomes. Data from the medical records were insufficient to explain the reasons for substandard outcome in all cases, thus emphasizing the need to examine also patient- and system-related variables not evident in the medical record. An approach to quality assurance that is based on measuring outcome and then determining the reasons for poor outcome in useful for uncovering correctable errors in the delivery of primary care. In order for the approach to be effective in improving care, the outcome measures used must be sensitive to the role of primary care in assisting partients to resolve health problems.

Diagnosing potential noncompliance. Physicians' ability in a behavioral dimension of medical care.

Predictions by housestaff physicians of whether or not patients would return for follow-up visits and of the amount of prescribed medication they would take were compared to measured compliance for 187 patients discharged from the medical service. Although physicians were able to predict visit compliance better than by chance alone, at best they could accurately predict only 35% of the noncompliers and one half of their predictions of noncompliance were incorrect. In predicting medication compliance, less than one half of physician predictions correctly discriminated between compliant and noncompliant patients and three fourths of their predictions of noncompliance were inaccurate. Because of physician limitations in this important clinical area, medical education should expand efforts to develop physician skills in diagnosing and managing sociobehavioral aspects of illness, and efforts to improve quality of care cannot ignore these "nontechnical" factors.

Quantitative tensile-tilting stages for the high voltage electron microscope.

This paper describes a soft and a hard tensile stage for the high voltage electron microscope. Both stages can be combined with a top entry double tilting stage. The devices are driven by thermal expansion elements operating against water cooled parts. The drive mechanism shows smooth action with a relatively low response time and good long-time stability. The stages are equipped with strain gauge bridges for force and elongation measurements. The soft stage has a maximum load of 13 g, and a hard one reaches 1.5 kg.

Extramedical factors in the decision to hospitalize medical patients.

This study assesses the importance of extramedical factors in the decision to hospitalize medical patients. Residents in a municipal hospital's emergency room completed a questionnaire on 252 consecutive patients at the time of admission. Extramedical factors contributed to the admission decision in 54 patients (21 percent); for twenty of these patients (8 percent of total) extramedical factors were the primary reason for admission. Factors noted most frequently related to patient behavior, such as being unlikely to follow instructions, and to home situations, such as social isolation. For 16 percent of the admissions, physicians felt that treatment outside the hospital was possible if realistic alternatives existed. Results suggest that extramedical factors are important contributors to the need for hospitalization. Attempts to develop quality assurance criteria, such as in utilization review or admission certification, must take such factors into account.

Management of hypertension. Effect of improving patient compliance for follow-up care.

A radomized controlled trial was conducted in a metropolitan teaching hospital to determine whether improving follow-up of emergency room patients who had hypertension led to improvements in their medical care and blood pressure control. One hundred fourty four patients were randomly assigned into an intervention group and a control group. In the former, a follow-up clerk assigned patients in returning for follow-up care. Eighty-four percent of patients in this group and 63% of control patients returned to the clinic (P less than 0.1). However, five months after the patients' emergency room visits, 51% of patients in the intervention group and 53% of control patients were normotensive. There were more diagnostic and therapeutic measures in the intervention group, but long-term management was similar in both groups. Improvement in follow-up may not be by itself lead to blood pressure control among hypertensive patients.