Riding the waves from epidemic to endemic: Viral mutations, immunological change and policy responses.

Nonpharmaceutical interventions (NPI) are an important tool for countering pandemics such as COVID-19. Some are cheap; others disrupt economic, educational, and social activity. The latter force governments to balance the health benefits of reduced infection and death against broader lockdown-induced societal costs. A literature has developed modeling how to optimally adjust lockdown intensity as an epidemic evolves. This paper extends that literature by augmenting the classic SIR model with additional states and flows capturing decay over time in vaccine-conferred immunity, the possibility that mutations create variants that erode immunity, and that protection against infection erodes faster than protecting against severe illness. As in past models, we find that small changes in parameter values can tip the optimal response between very different solutions, but the extensions considered here create new types of solutions. In some instances, it can be optimal to incur perpetual epidemic waves even if the uncontrolled infection prevalence would settle down to a stable intermediate level.

The hammer and the jab: Are COVID-19 lockdowns and vaccinations complements or substitutes?

The COVID-19 pandemic has devastated lives and economies around the world. Initially a primary response was locking down parts of the economy to reduce social interactions and, hence, the virus' spread. After vaccines have been developed and produced in sufficient quantity, they can largely replace broad lock downs. This paper explores how lockdown policies should be varied during the year or so gap between when a vaccine is approved and when all who wish have been vaccinated. Are vaccines and lockdowns substitutes during that crucial time, in the sense that lockdowns should be reduced as vaccination rates rise? Or might they be complementary with the prospect of imminent vaccination increasing the value of stricter lockdowns, since hospitalization and death averted then may be permanently prevented, not just delayed? We investigate this question with a simple dynamic optimization model that captures both epidemiological and economic considerations. In this model, increasing the rate of vaccine deployment may increase or reduce the optimal total lockdown intensity and duration, depending on the values of other model parameters. That vaccines and lockdowns can act as either substitutes or complements even in a relatively simple model casts doubt on whether in more complicated models or the real world one should expect them to always be just one or the other. Within our model, for parameter values reflecting conditions in developed countries, the typical finding is to ease lockdown intensity gradually after substantial shares of the population have been vaccinated, but other strategies can be optimal for other parameter values. Reserving vaccines for those who have not yet been infected barely outperforms simpler strategies that ignore prior infection status. For certain parameter combinations, there are instances in which two quite different policies can perform equally well, and sometimes very small increases in vaccine capacity can tip the optimal solution to one that involves much longer and more intense lockdowns.

Regulation of conduction time along axons.

Timely delivery of information is essential for proper functioning of the nervous system. Precise regulation of nerve conduction velocity is needed for correct exertion of motor skills, sensory integration and cognitive functions. In vertebrates, the rapid transmission of signals along nerve fibers is made possible by the myelination of axons and the resulting saltatory conduction in between nodes of Ranvier. Myelin is a specialization of glia cells and is provided by oligodendrocytes in the central nervous system. Myelination not only maximizes conduction velocity, but also provides a means to systematically regulate conduction times in the nervous system. Systematic regulation of conduction velocity along axons, and thus systematic regulation of conduction time in between neural areas, is a common occurrence in the nervous system. To date, little is understood about the mechanism that underlies systematic conduction velocity regulation and conduction time synchrony. Node assembly, internode distance (node spacing) and axon diameter - all parameters determining the speed of signal propagation along axons - are controlled by myelinating glia. Therefore, an interaction between glial cells and neurons has been suggested. This review summarizes examples of neural systems in which conduction velocity is regulated by anatomical variations along axons. While functional implications in these systems are not always clear, recent studies on the auditory system of birds and mammals present examples of conduction velocity regulation in systems with high temporal precision and a defined biological function. Together these findings suggest an active process that shapes the interaction between axons and myelinating glia to control conduction velocity along axons. Future studies involving these systems may provide further insight into how specific conduction times in the brain are established and maintained in development. Throughout the text, conduction velocity is used for the speed of signal propagation, i.e. the speed at which an action potential travels. Conduction time refers to the time it takes for a specific signal to travel from its origin to its target, i.e. neuronal cell body to axonal terminal.

First Report of Late Blight Caused by Phytophthora infestans Clonal Lineage US-24 on Potato (Solanum tuberosum) in Wisconsin.

Potato (Solanum tuberosum) crops are grown on over 25,090 ha in Wisconsin annually. Late blight, caused by Phytophthora infestans (Mont.) deBary, is a potentially devastating disease that affects tomato and potato crops in Wisconsin every few years when inoculum is introduced and weather conditions favor disease. Incidence and severity of late blight are highly variable in these few years due to differences in pathogen clonal lineages, their timing and means of introduction, and weather conditions. Prevention of this disease through prophylactic fungicide application can cost producers millions of dollars annually in additional chemical, fuel, and labor expenses. Populations of P. infestans in the U.S. have recently undergone significant genetic change, resulting in isolates with unique clonal lineages and epidemiological characteristics (1). In 2010, late blight epidemics were of low severity in discrete portions of a few fields and were seen exclusively on potato in two counties of central Wisconsin. Symptoms included water-soaked to dark brown circular lesions with pale green haloes accompanied by white fuzzy pathogen sporulation typically on leaf undersides in high humidity conditions. Infected plants were collected by professional crop consultants and submitted to the authors at the University of Wisconsin Vegetable Pathology Laboratory in Madison, Wisconsin. Eight isolates of P. infestans were generated from individual leaf samples, representing separate fields, by removing sporangia from sporulating lesions and placing onto Rye A agar amended with rifampicin and ampicillin. Axenic, single zoospore-derived cultures of isolates were generated from parent cultures and maintained on Rye A agar for further characterization. Mycelium was coenocytic with hyphal diameter of 5 to 8 µm (n = 50). Sporangia were limoniform to ovoid, semi- to fully papillate, caducous, had short pedicels, and were 36.22 × 19.11 µm (height × width; n = 50). The average length-width ratio was 1.91. Allozyme banding patterns at the glucose-6-phosphate isomerase (Gpi) locus indicated a 100/100/111 profile, consistent with the US-24 clonal lineage (3,4). Mating type assays confirmed the isolates to be A1 and intermediate insensitivity to mefenoxam was observed in vitro (4). Genomic DNA was extracted with a phenol:chloroform:isoamyl alcohol solution and restriction fragment length polymorphism (RFLP) analysis was performed using the RG-57 probe on a representative isolate and resulted in banding patterns consistent with US-24 (2,3). Clonal lineages of P. infestans documented in Wisconsin in previous epidemics included US-8 in the mid-1990s and US-1 in the 1970s. The US-24 (A1) clonal lineage was very widespread in the U.S. in 2010 and its presence in Wisconsin in the same year as identification of US-22 (A2) posed great concern for potential sexual recombination, oospore production, and soil persistence. Fortunately, the opposite mating types were separated spatiotemporally. To the best of our knowledge, this is the first report of the P. infestans clonal lineage US-24 causing late blight on potato in Wisconsin. References: (1) K. Deahl. (Abstr.) Phytopathology 100:S161, 2010. (2) S. B. Goodwin et al. Curr. Genet. 22:107, 1992. (3) Hu et al. Plant Dis. 96:1323, 2012. (4) A. C. Seidl and A. J. Gevens. (Abstr.) Phytopathology 101:S162, 2011.

First Report of Late Blight Caused by Phytophthora infestans Clonal Lineage US-22 on Tomato and Potato in Wisconsin.

Tomato (Solanum lycopersicum) and potato (S. tuberosum) crops are grown on over 67,000 acres (27,114 hectares) in the state of Wisconsin each year. Late blight, caused by Phytophthora infestans (Mont.) deBary, is a potentially devastating oomycete pathogen that sporadically affects tomato and potato crops in the state. Prevention of this disease through prophylactic application of oomycete-specific fungicides can cost producers millions of dollars per year in additional chemical, fuel, and labor expenses. In 2009, late blight was observed on tomato and potato in over 25 Wisconsin counties. The epidemic initiated on tomato in southern WI in early August and progressed northward in the state with additional reports on tomato primarily from home gardens and small farms. Potato late blight was also identified but with limited incidence in central WI, likely due to routine fungicide programs in commercial production. Clonal lineages of P. infestans documented in Wisconsin in previous epidemics included US-1 in the 1970s and US-8 in the mid-1990s. Populations of P. infestans in the U.S. have recently undergone significant genetic changes, resulting in isolates with unique clonal lineages and epidemiological characteristics (1). Symptoms of late blight observed on tomato and potato included water-soaked to dark brown circular lesions with pale green haloes accompanied by signs of pathogen sporulation typically on leaf undersides during periods of high humidity. Isolates of P. infestans were generated from field infected tomato and potato foliar tissues. Axenic, single zoospore derived cultures were generated and maintained on Rye A agar for further characterization. Mycelium was coenocytic with hyphal diameter of 5 to 8 µm (n = 50). Sporangia were limoniform or ovoid, semi- to fully papillate, caducous, had short pedicels, and were 29.6 (h) × 16.8 µm (w) (n = 50). The average length/width ratio was 1.76. Allozyme banding patterns at the glucose-6-phosphate isomerase (Gpi) locus indicated a 100/122 profile, consistent with the US-22 clonal lineage (3). Mating type assays confirmed the isolates to be A2 and in vitro mefenoxam sensitivity was observed (4). Restriction fragment length polymorphic analysis of a representative isolate from Wisconsin with the multilocus RG57 sequence and EcoRI produced the DNA pattern indicative of US-22 (2). The P. infestans clonal lineage US-22 was predominant in U.S. epidemics on tomato in 2009. To our knowledge, this is the first report of P. infestans clonal lineage US-22 causing late blight on tomato and potato in Wisconsin, USA. References: (1) K. Deahl. (Abstr.) Phytopathology 100(suppl.):S161, 2010. (2) S. B. Goodwin et al. Curr. Genet. 22:107, 1992. (3) C. H. Hu et al. Plant Dis. 96:1323, 2012. (4) A. C. Seidl et al. Phytopathology 101(suppl.):S246, 2011.

First Report of Late Blight Caused by Phytophthora infestans Clonal Lineage US-23 on Tomato and Potato in Wisconsin, United States.

Tomato (Solanum lycopersicum) and potato (S. tuberosum) crops are grown on over 67,000 acres (27,114 ha) in Wisconsin annually. Late blight, caused by Phytophthora infestans (Mont.) deBary, is a potentially devastating disease that affects tomato and potato crops in Wisconsin every few years when inoculum is introduced and weather conditions favor disease. Incidence and severity of late blight are highly variable in these few years due to differences in pathogen clonal lineages, their timing and means of introduction, and weather conditions. Prevention of this disease through preventative application of fungicides can cost producers millions of dollars per year in additional chemical, fuel, and labor expenses. In 2009, late blight caused by P. infestans clonal lineage US-23 was observed on potato very late in the season in Vernon County, southwestern Wisconsin, in very low incidence and severity. In 2010, US-23 again appeared but on tomato in two southeastern Wisconsin counties, Waukesha and Ozaukee, again in low incidence and severity. Clonal lineages of P. infestans documented in Wisconsin in previous epidemics included US-8 in the mid-1990s and US-1 in the 1970s. Populations of P. infestans in the United States have recently undergone significant genetic change, resulting in isolates with unique clonal lineages and epidemiological characteristics (1). Foliar symptoms included water-soaked to dark brown circular lesions with pale green haloes accompanied by white pathogen sporulation. On tomato fruit, lesions were firm, sunken, and brown. Isolates of P. infestans were generated from field-infected tomato and potato foliar and fruit tissues collected by the authors and professional crop consultants. In initial pathogen confirmation analysis in 2009, three isolates of P. infestans were generated from one potato plant exhibiting multiple lesions from one of eight fields tested by placing infected leaf excisions onto Rye A agar amended with rifampicin and ampicillin. Axenic, single zoospore-derived cultures of isolates were generated from parent cultures and maintained on Rye A agar for further characterization. In 2010, three US-23 isolates were recovered from three locations (two counties), out of 20 fields tested. Mycelium was coenocytic with hyphal diameter of 5 to 8 µm (n = 50). Sporangia were limoniform or ovoid, semi to fully papillate, caducous, had short pedicels, and were 26.16 µm high × 18.17 µm wide (n = 50). The average length/width ratio was 1.42. Allozyme banding patterns at the glucose-6-phosphate isomerase (Gpi) locus indicated a 100/100 profile, consistent with the US-23 clonal lineage (3) Mating type assays confirmed the isolates to be A1 and in vitro intermediate mefenoxam sensitivity was observed (4). Genomic DNA was extracted with a phenol/chloroform/isoamyl alcohol solution and RFLP analysis was performed using the RG-57 probe on a representative isolate and resulted in banding patterns consistent with US-23 (2,3). The P. infestans clonal lineage US-23 was present in epidemics in 2009 and 2010 in the United States. Disease symptoms associated with US-23 were observed exclusively on potato in 2009 and on tomato in 2010 in Wisconsin. To our knowledge, this is the first report of P. infestans clonal lineage US-23 causing late blight on tomato and potato in Wisconsin and represents a change in the composition of the pathogen population from previous epidemic years. References: (1) K. Deahl. (Abstr.) Phytopathology 100:S161, 2010. (2) S. B. Goodwin et al. Curr. Genet. 22:107, 1992. (3) Hu et al. Plant Dis. 96:1323, 2012. (4) A. C. Seidl and A. J. Gevens. (Abstr.) Phytopathology 101(suppl.):S162, 2011.

[IQWiG's methods for the cost-benefit assessment : Comparison with an international reference scenario]. / Wo steht die Kosten-Nutzen-Bewertung des IQWiG : Abgleich mit einem internationalen Referenzszenario?

Standardization of international health economic guidelines has been repeatedly requested. In this context, an international reference case was proposed, which constitutes an agreed approach for the key elements of health economic evaluation including study perspective, comparators, source of effectiveness data, role of modeling, main (economic) outcome, source of utilities, characterizing uncertainty. It is, however, questionable whether such a reference scenario can reasonably be applied across all health care systems. Our analysis pursues the question to which degree the Institute for Quality and Efficiency in Health Care's (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, IQWiG) "General methods for evaluating the relation between cost and benefit" comply with the key elements of the reference case. In case of divergences, they will be described and discussed in light of the German social legislation and in consideration of current scientific evidence. In conclusion, the analysis revealed that IQWiG complied with the reference case in almost all aspects. Differences were found only with respect to the choice of main (economic) outcome and the source of utilities. These differences seem justified and well explained in the context of the German social legislation as well as in view of the weaknesses of the quality-adjusted life year (QALY) concept.

Trypanosoma evansi control and horse mortality in the Brazilian Pantanal.

The impact of three treatment strategies for Trypanosoma evansi control on horse mortality in the Brazilian Pantanal based on four size categories of cattle ranches is explored. The region's 49,000 horses are indispensable to traditional extensive cattle ranching and T. evansi kills horses. About 13% of these horses would be lost, annually, due to T. evansi if no control were undertaken. One preventive and two curative treatment strategies are financially justifiable in the Pantanal. The best available technology for the treatment of T. evansi from a horse mortality perspective is the preventive strategy, which spares 6,462 horses, annually. The year-round cure spares 5,783 horses, and the seasonal cure saves 5,204 horses on a regional basis relative to no control strategy. Regardless of the strategy adopted, 39% of the costs or benefits fall to the largest ranches, while 18% fall to the smallest ranches.

Trypanosoma evansi control and horse mortality in the Brazilian Pantanal

The impact of three treatment strategies for Trypanosoma evansi control on horse mortality in the Brazilian Pantanal based on four size categories of cattle ranches is explored. The region's 49,000 horses are indispensable to traditional extensive cattle ranching and T. evansi kills horses. About 13 percent of these horses would be lost, annually, due to T. evansi if no control were undertaken. One preventive and two curative treatment strategies are financially justifiable in the Pantanal. The best available technology for the treatment of T. evansi from a horse mortality perspective is the preventive strategy, which spares 6,462 horses, annually. The year-round cure spares 5,783 horses, and the seasonal cure saves 5,204 horses on a regional basis relative to no control strategy. Regardless of the strategy adopted, 39 percent of the costs or benefits fall to the largest ranches, while 18 percent fall to the smallest ranches

Estimated financial impact of Trypanosoma vivax on the Brazilian pantanal and Bolivian lowlands.

The financial impact of the first outbreak of Trypanosoma vivax in the Brazilian Pantanal wetland is estimated. Results are extended to include outbreaks in the Bolivian lowlands providing a notion of the potential influence of the disease and an analytical basis. More than 11 million head of cattle, valued at more than US$3 billion are found in the Brazilian Pantanal and Bolivian lowlands. The total estimated cost of the 1995 outbreak of T. vivax is the sum of the present values of mortality, abortion, and productivity losses and treatment costs, or about 4% of total brood cow value on affected ranches. Had the outbreak gone untreated, the estimated losses would have exceeded 17% of total brood cow value.

A financial analysis of treatment strategies for Trypanosoma evansi in the Brazilian Pantanal.

The Brazilian Pantanal is a 138,000 km2 tropical seasonal wetland located in the center of South America bordering Bolivia and Paraguay. The Pantanal contains approximately 1100 cattle ranches, 3 million cattle, 49,000 horses and a unique diversity of wildlife. Cattle ranching is the most important economic activity in the Pantanal. This study explores the direct financial impacts of the adoption of seven treatment strategies for the control of Trypanosoma evansi in the Brazilian Pantanal. T. evansi adversely affects the health of the horse population in the region. Horses are indispensable to the cattle ranching industry in the Pantanal. Estimated costs include risk of infection, costs of diagnosis, alternative treatments, collecting animals for treatment, and costs of animal losses. The estimated total cost of T. evansi to the Pantanal region's cattle ranchers is about US$2.4 million and 6462 horses/yr. Results indicate that one preventive and two curative treatment strategies are financially justifiable. The best available technology for the treatment of T. evansi from an economic perspective is a curative treatment employed year-round. This treatment represents an annual net benefit of more than US$2 million or US$1845/ranch and spares about 5783 horses. It represents an annual net benefit of over US$200,000 and 600 horses relative to the currently most widely adopted strategy.

Nurses' attitudes toward emotional, sexual, and physical abusers of children with disabilities.

Some studies have linked birth defects, disability, and chronic illness with an increased incidence of child abuse. Nurses who are involved with disabled children face a challenge in preventing child abuse and intervening in cases in which abuse has occurred. Nurse must become aware of the risk factors and signs of abuse, understand the role of their personal attitudes toward abuse and abusers, and develop the skills to intervene effectively and deal with abusers. Thus, the authors of this article undertook a study to ascertain nurses' attitudes about emotional, sexual, and physical abuse of children with disabilities and to determine if nurses' anticipated level of comfort differed when dealing with abusers of children with disabilities in contrast to abusers of children without disabilities.

GAS TRANSPORT IN THE HAEMOLYMPH OF ARACHNIDS - OXYGEN TRANSPORT AND THE PHYSIOLOGICAL ROLE OF HAEMOCYANIN

Oxygen equilibrium curves and the relationships between the partial pressure of CO2 and pH were determined for the haemolymph of the arachnids Eurypelma californicum, Pandinus imperator and Cupiennius salei. A new type of experimental apparatus was constructed, tested and used to make these measurements on small undiluted cell-free haemolymph samples. Most of its components were made in our workshop and were inexpensive. The apparatus proved to be very reliable as demonstrated by control (oxygen concentration) experiments. In previous reports on O2 equilibrium curves of E. californicum haemocyanin, Tris­HCl buffer was used to set the pH, whereas in our experiments, pH was adjusted by altering the partial pressure of CO2. The O2 concentration measurements demonstrate an increase in oxygen affinity of E. californicum haemocyanin when using Tris­HCl buffer. The position and shape of the O2 equilibrium curves of E. californicum and P. imperator haemocyanin show a distinct dependency on pH. Oxygen affinity is lower in E. californicum and cooperativity changes with pH in E. californicum, but not in P. imperator. Oxygen transport in the haemolymph of E. californicum during rest, activity and recovery was calculated on the basis of the O2 equilibrium curves of undiluted haemolymph. Apart from oxygen transport, there are indications that haemocyanin is also involved in other physiological processes. For example, it may function as a storage protein.

GAS TRANSPORT IN THE HAEMOLYMPH OF ARACHNIDS - CARBON DIOXIDE TRANSPORT AND ACID-BASE BALANCE

The relationships between PCO2 and pH were determined in cell-free undiluted haemolymph of the arachnids Eurypelma californicum, Pandinus imperator and Cupiennius salei. The pH/bicarbonate diagrams and the CO2 equilibrium curves were calculated, using the Henderson­Hasselbalch equation, for haemolymph sampled at rest and during recovery from exercise. The calculations of solubility (alphaCO2) and dissociation constant (pK"') were based on additional ion concentration measurements. Blood gas analyses corroborate these results: after locomotor activity, there is a metabolic acidosis linked to the accumulation of lactate in the haemolymph. The concentration of bicarbonate in the haemolymph of resting individuals is quite different in the three species and is related to the extent of post-exercise bicarbonate depletion. During early recovery, buffering in the haemolymph strongly depends upon CO2 release. Potassium and magnesium concentrations in the haemolymph increase after exercise. During cold-acclimation (to 10 °C), there is a metabolic acidosis in the tarantula's haemolymph that is linked to the accumulation of acetate.

Parent gender, victim gender, and family socioeconomic level influences on the potential reporting by nurses of physical child abuse.

In 1974, the Federal Child Abuse Prevention and Treatment Act required reporting of child abuse in all states. Although nurses have since this time been designated as mandated reporters of abuse, only recently have nurses begun to hold positions where they are directly responsible for abuse reporting. This study investigated whether the gender of the victim, the gender of the abusing parent, or the family's socioeconomic level influences the potential reporting of child abuse by nurses. Participants were shown three vignettes of children being admitted to an emergency room with symptoms of possible abuse. When asked if they would or would not report the incident as child abuse, participants indicated they were significantly less apt to report abuse when the victim was female rather than male, and when the family was perceived as being from a middle rather than a low or high socioeconomic background. The implication of this finding is that female children from middle-class backgrounds may be left less protected than others as nurses become more actively involved in child abuse reporting.

A short-term geriatric nursing programme in the US for Japanese Nurses.

Providing quality care to their growing elderly population is a top priority for Japanese nurses. As geriatric nursing has become a significant subspecialty in the US, this expertise was sought by the Japanese Hospital Administration in collaboration with Kyoto University. The result: a geriatric nursing programme developed to meet the specific needs of Japanese nurses in caring for the elderly, but yet adaptable to meet the needs of nursing students and registered nurses in other countries.