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Background: End-stage liver disease (ESLD) patients carry heavy symptom burdens and risk receiving aggressive and sometimes unwanted care at end of life. Palliative care (PC), which aims to alleviate symptoms and facilitate goal-concordant care in serious illness, may offer substantial benefits for ESLD patients but is not widely provided. Objectives: To assess the impact of PC integrated within hepatology (PCIH) services on health care utilization, advance care planning (ACP), and hospice enrollment. Design: We compared patients who received PCIH (n = 55) to a retrospective cohort (n = 57) receiving usual care in an outpatient hepatology clinic. Setting/Subjects: From June 2016 to November 2017, we enrolled patients receiving care in a U.S. public hospital clinic who met the following inclusion criteria: (1) ESLD with a Model for End-Stage Liver Disease score ≥20, (2) hepatology approval for PC referral, and (3) at least one advanced complication of ESLD. Measurements: We assessed patient demographics, clinical information, health care insurance status, health care utilization, completion of psychosocial assessments, and ACP using two-sided Fisher's exact test and Mann-Whitney U tests. Results: Patients receiving PCIH more frequently had goals of care discussions (87.3% vs. 21.2% p ≤ 0.01), completed ACP documentation (56.4% vs. 7.0%, p ≤ 0.01), psychosocial assessments (98.2% vs. 35.1%, p ≤ 0.01), and hospice enrollment (25.5% vs. 7.0%, p = 0.01). Patients receiving PCIH who were hospitalized also had fewer mean hospitalization days (13 vs. 19.7 days, p ≤ 0.01). Conclusions: Embedding PC services in a hepatology clinic is a promising strategy to improve care for ESLD patients in public hospitals.

BACKGROUND: Post-exertional malaise (PEM) is the hallmark symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) yet its diverse manifestations make it difficult to recognize. Brief instruments for detecting PEM are critical for clinical and scientific progress. OBJECTIVE: To develop a clinical prediction rule for PEM. METHOD: 49 ME/CFS and 10 healthy, sedentary subjects recruited from the community completed two maximal cardiopulmonary exercise tests (CPETs) separated by 24 hours. At five different times, subjects reported symptoms which were then classified into 19 categories. The frequency of symptom reports between groups at each time point was compared using Fisher’s exact test. Receiver operating characteristics (ROC) analysis with area under the curve calculation was used to determine the number of different types of symptom reports that were sufficient to differentiate between ME/CFS and sedentary groups. The optimal number of symptoms was determined where sensitivity and specificity of the types of symptom reports were balanced. RESULTS: At all timepoints, a maximum of two symptoms was optimal to determine differences between groups. Only one symptom was necessary to optimally differentiate between groups at one week following the second CPET. Fatigue, cognitive dysfunction, lack of positive feelings/mood and decrease in function were consistent predictors of ME/CFS group membership across timepoints. CONCLUSION: Inquiring about post-exertional cognitive dysfunction, decline in function, and lack of positive feelings/mood may help identify PEM quickly and accurately. These findings should be validated with a larger sample of patients.

Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS. In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS. This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) can cause a wide range of severity and functional impairment, leaving some patients able to work while others are homebound or bedbound. The most severely ill patients may need total care. Yet, patients with severe or very severe ME/CFS struggle to receive appropriate medical care because they cannot travel to doctors’ offices and their doctors lack accurate information about the nature of this disease and how to diagnose and manage it. Recently published clinical guidance provides updated information about ME/CFS but advice on caring for the severely ill is limited. This article is intended to fill that gap. Based on published clinical guidance and clinical experience, we describe the clinical presentation of severe ME/CFS and provide patient-centered recommendations on diagnosis, assessment and approaches to treatment and management. We also provide suggestions to support the busy provider in caring for these patients by leveraging partnerships with the patient, their caregivers, and other providers and by using technology such as telemedicine. Combined with compassion, humility, and respect for the patient’s experience, such approaches can enable the primary care provider and other healthcare professionals to provide the care these patients require and deserve.

Adult patients affected by myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are at an increased risk of death by suicide. Based on the scientific literature and our clinical/research experiences, we identify risk and protective factors and provide a guide to assessing and managing suicidality in an outpatient medical setting. A clinical case is used to illustrate how information from this article can be applied. Characteristics of ME/CFS that make addressing suicidality challenging include absence of any disease-modifying treatments, severe functional limitations, and symptoms which limit therapies. Decades-long misattribution of ME/CFS to physical deconditioning or psychiatric disorders have resulted in undereducated healthcare professionals, public stigma, and unsupportive social interactions. Consequently, some patients may be reluctant to engage with mental health care. Outpatient medical professionals play a vital role in mitigating these effects. By combining evidence-based interventions aimed at all suicidal patients with those adapted to individual patients’ circumstances, suffering and suicidality can be alleviated in ME/CFS. Increased access to newer virtual or asynchronous modalities of psychiatric/psychological care, especially for severely ill patients, may be a silver lining of the COVID-19 pandemic.

Background Today, 24% of college and university students are affected by a chronic health condition or disability. Existing support programs, including disability services, within colleges and universities are often unaccustomed to addressing the fluctuating and unpredictable changes in health and functioning faced by students with severe chronic illnesses. This situation is especially difficult for students with lesser-known, invisible diseases like Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a complex disease affecting up to 2.5 million Americans which often begins in late adolescence or young adulthood. Objective Educate occupational therapists (OTs) about ME/CFS and steps they can take to assist students. Methods This work is based on a review of the scientific literature and our collective professional/ personal experiences. Results ME/CFS' effects on multiple organ systems combined with the unusual symptom of post-exertional malaise frequently and substantially decrease function. Currently, no effective disease-modifying treatments have been established. Nevertheless, OTs can help student maximize their participation in university life by identifying potential obstacles, formulating practical solutions and negotiating with their institutions to implement reasonable, environmental accommodations. Conclusions Through understanding this disease, being aware of possible support options, and recommending them as appropriate, OTs are in unique position to greatly improve these students' lives.

Differences of opinion about how case definitions are operationalized should not be characterized as ‘mistaken.’ Despite limitations, our study provides insight into how systemic exertion intolerance disease (SEID) criteria perform early in the course of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) compared to other case definitions. To facilitate early, accurate diagnosis, research needs to be performed, ideally, prospectively with subjects who have not been ill for years. In addition, results of past treatment studies may not be applicable to many ME/CFS patients because criteria used for research differed from patients’ clinical presentations. To avoid this potential mismatch between research employing the new clinically-focused SEID criteria should be promoted, rather than discouraged.

Background: Myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) remains undiagnosed in up to 91% of patients. Recently, the United States-based Institute of Medicine (IOM) developed new diagnostic criteria, naming it systemic exertion intolerance disease (SEID).Purpose: We examined how subjects fit SEID criteria and existing ME/CFS case definitions early in their illness.Methods: A total of 131 subjects fitting 1994 Fukuda CFS criteria at the time of study recruitment completed a survey of symptoms they experienced during their first 6 months of illness. Symptoms were drawn from SEID and existing criteria (1994 Fukuda, 2003 Canadian Consensus Criteria (CCC), and 2011 Myalgic Encephalomyelitis-International Consensus Criteria (ME-ICC)). We calculated and compared the number/percentage of subjects fitting single or combinations of case definitions and the number/percentage of subjects with SEID experiencing orthostatic intolerance (OI) and/or cognitive impairment.Results: At 6 months of ill...

A significant challenge of traditional glycan mapping techniques is that they do not provide site-specific glycosylation information. Therefore, for proteins containing multiple glycosylation sites, the individual glycan species present at a particular site cannot be differentiated from those species present at the other glycosylation sites on the molecule. Quantification of glycoform has previously been demonstrated using a multiattribute method (MAM), which can quantify multiple post-translational modifications including deamidation, oxidation, glycosylation variants, and fragmentation ( Rogers, R. S.; Nightlinger, N. S.; Livingston, B.; Campbell, P.; Bailey, R.; Balland, A. MAbs 2015 , 7 , 881 - 890 ; ref 1). In this paper we describe the application of an MAM based method for site specific quantification of N-linked glycan heterogeneity present on an IgG1 mAb molecule containing two distinct N-linked glycosylation sites: one present on the heavy chain (HC) variable region (Fab) and the other present on the conserved HC constant region (Fc). MAM is a peptide mapping method utilizing mass spectrometry to detect and quantify specific peptides of interest. The ionization properties of the glycopeptides with different classes of glycan structural variants, including high mannose, sialylated, and terminal galactosylated species were studied in detail. Our results demonstrate that MAM quantification of individual glycan species from both the Fab and Fc N-Linked glycosylation sites is consistent with quantification using the traditional hydrophilic interaction liquid chromatography (HILIC) analysis of enzymatically released and fluorescently labeled glycans. Furthermore, no significant impact from the glycoform on the ionization properties of the glycopeptide is observed. Our work demonstrates that the MAM method is a suitable approach for providing quantitative, site-specific glycan information for profiling of N-linked glycans on immunoglobulins.

Background: Epidemiologic studies of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) have examined different aspects of this disease separately but few have explored them together. Objective: Describe ME/CFS onset and course in one United States-based cohort. Methods: One hundred and fifty subjects fitting Fukuda 1994 CFS criteria completed a detailed survey concerning the initial and subsequent stages of their illness. Descriptive statistics, graphs, and tables were used to illustrate prevalence and patterns of characteristics. Results: The most common peri-onset events reported by subjects were infection-related episodes (64%), stressful incidents (39%), and exposure to environmental toxins (20%). For 38% of subjects, more than 6 months elapsed from experiencing any initial symptom to developing the set of symptoms comprising their ME/CFS. Over time, the 12 most common symptoms persisted but declined in prevalence, with fatigue, unrefreshing sleep, exertion-related sickness, and flu-like symptoms declining the most (by 20-25%). Conversely, cognitive symptoms changed the least in prevalence, rising in symptom ranking. Pregnancy, menopause, and menstrual cycles exacerbated many women's symptoms. Fatigue-related function was not associated with duration of illness or age; during the worst periods of their illness, 48% of subjects could not engage in any productive activity. At the time of survey, 47% were unable to work and only 4% felt their condition was improving steadily with the majority (59%) describing a fluctuating course. Ninety-seven percent suffered from at least one other illness: anxiety (48%), depression (43%), fibromyalgia (39%), irritable bowel syndrome (38%), and migraine headaches (37%) were the most diagnosed conditions. Thirteen percent came from families where at least one other first-degree relative was also afflicted, rising to 27% when chronic fatigue of unclear etiology was included. Conclusions: This paper offers a broad epidemiologic overview of one ME/CFS cohort in the United States. While most of our findings are consistent with prior studies, we highlight underexamined aspects of this condition (e.g., the evolution of symptoms) and propose new interpretations of findings. Studying these aspects can offer insight and solutions to the diagnosis, etiology, pathophysiology, and treatment of this condition.

Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

Background Post-exertional malaise (PEM) is considered to be the hallmark characteristic of myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). Yet, patients have rarely been asked in formal studies to describe their experience of PEM. Objectives To describe symptoms associated with and the time course of PEM Methods One hundred and fifty subjects, diagnosed via the 1994 Fukuda CFS criteria, completed a survey concerning 11 symptoms they could experience after exposure to two different types of triggers. We also inquired about onset and duration of PEM and included space for subjects to write in any additional symptoms. Results were summarized with descriptive statistics; McNemar’s, paired t-, Fisher’s exact and chi-square goodness-of-fit tests were used to assess for statistical significance. Results One hundred and twenty-nine subjects (90%) experienced PEM with both physical and cognitive exertion and emotional distress. Almost all were affected by exertion but 14 (10%) reported no effect with emotion. Fatigue was the most commonly exacerbated symptom but cognitive difficulties, sleep disturbances, headaches, muscle pain, and flu-like feelings were cited by over 30% of subjects. Sixty percent of subjects experienced at least one inflammatory/ immune-related symptom. Subjects also cited gastrointestinal, orthostatic, mood-related, neurologic and other symptoms. Exertion precipitated significantly more symptoms than emotional distress (7±2.8 vs. 5±3.3 symptoms (median, standard deviation), p

Glycation of immunoglobulin G (IgG) can result from incubation with a reducing sugar in vitro or during circulation in vivo. Upon injection of a recombinantly produced human therapeutic IgG into humans, changes in the glycation levels could be observed as a function of circulation time. Mass changes on the individual IgG polypeptide chains as the results of glycation were determined using reversed-phase liquid chromatography/mass spectrometry. Changes to the light and heavy chains were low but easily detectable at 0.00092 and 0.0021 glucose (Glc) additions per chain per day, respectively. Levels of glycation found on the Fc portion of IgG isolated from healthy subjects, using a similar analytical approach, were on average 0.045 Glc molecules per fragment. In vivo glycation rates could be approximated in vitro by modeling the physiological glycation reaction with a simplified incubation containing physiological Glc concentrations, pH and temperature but with a high concentration of a single purified IgG. To test the impact of glycation on IgG function, highly glycated IgG1 and IgG2 were prepared containing on average 42-49 Glc molecules per IgG. Binding to FcγIIIa receptors, neonatal Fc receptor or protein A was similar or identical to the non-glycated IgG controls. Although the modifications were well distributed throughout the protein sequence, and at high enough levels to affect the elution position by size-exclusion chromatography, no changes in the tested Fc functions were observed.

According to Dede Bonner in 2000, employees hold a wealth of knowledge and experience about their companies, including the products, customers, internal processes, histories, technologies, and competitors. But this knowledge is usually dispersed across scattered individuals and locations. Although learning happens at an individual level, it is usually as a one-time event, without an organizational context or a sense of continuity. Knowledge is kept in people's minds but not shared in an organization. Not until the 20th century did people start to realize that knowledge is critical to the success of a company and considered to be the pivotal point for aggressive organizational growth in today's highly competitive marketplace. This is also true for the Hong Kong construction industry. In order to gain a deeper understanding of the current situation of knowledge sharing at the departmental level in contracting companies, this research was carried out with the aims of investigating the main barriers to and finding out the critical factors for and benefits resulting from effective knowledge sharing in the tendering departments of contracting companies in Hong Kong and the United Kingdom. The research reviews existing theories of knowledge and knowledge sharing. It seeks to contribute to the theory of organizational knowledge sharing by providing an explorative account supported by empirical evidence. It also allows management to continuously anticipate and support knowledge sharing activities related to the successful management of construction projects within their particular organizations.

Rectal thermometry, the criterion standard of temperature measurement in young children, has numerous disadvantages. This study examined the agreement between rectal versus a new temporal artery professional model (TAPM) thermometer and rectal versus a home device temporal artery consumer model (TACM) thermometer, investigated if the TAPM can safely screen for rectal fever, and determined if parents can detect rectal fever using the TACM. DESIGN, OUTCOME MEASURES, AND SUBJECTS: In this cross-sectional agreement emergency department study, 327 children24 months of age had their temperature measured rectally and by the TAPM and TACM by a single nurse and using the TACM by the parents. Agreements were analyzed by the Bland Altman plots. Temperature cutoff to detect rectal feveror =38.0 degrees C andor =38.3 degrees C with sensitivities ofor =90% andor =95%, respectively, was determined for the TAPM.The mean difference between the rectal minus TAPM was -0.19 degrees C +/- 0.66 degrees C, and minus the TACM home device, it was +0.11 degrees C +/- 0.66 degrees C. The sensitivities of TAPM temperature ofor =37.7 degrees C to detect rectal feveror =38.0 degrees C andor =38.3 degrees C were 90% (95% confidence interval: 0.83; 0.94) and 97% (95% confidence interval: 0.92; 0.99), respectively. The parents detected 67% and 73% of rectal fevers 38.0 degrees C andor =38.3 degrees C, respectively.The TAPM thermometer cannot replace the rectal. However, TAPM temperature of37.7 degrees C can be safely used as a screen to exclude rectal feveror =38.3 degrees C in infants 3 to 24 months of age. The TACM home device has insufficient ability to detect rectal fever. A multicenter trial is needed to validate these results across multiple emergency departments and numerous observers.

Traditional barriers to large-scale mammalian culture have now been addressed, with the standard stirred-tank reactor emerging as industry's technology of choice. The issues of adapting cells to suspension culture, shear sensitivity and oxygen supply have been largely resolved. But for many low-volume and specialty applications, such as the production of viral vaccines and gene therapies, reactor technology remains diversified, with reactor types ranging from roller bottles to stacked plates and hollow fibers.

Peptide growth factors and other receptor-binding cytokine ligands are of interest in contemporary molecular health care approaches in applications such as wound healing, tissue regeneration, and gene therapy. Development of effective technologies based on operation of these regulatory molecules requires an ability to deliver the ligands to target cells in a reliable and wellcharacterizable manner. Quantitative information concerning the fate of peptide ligands within tissues is necessary for adequate interpretation of experimental observations at the tissue level and for truly rational engineering design of ligand-based therapies. To address this need, we are undertaking efforts to elucidate effects of key molecular and cellular parameters on temporal and spatial distribution of cytokines in cell population and cell/matrix systems. In this article we summarize some of our recent findings on dynamics of growth factor depletion by cellular endocytic trafficking, growth factor transport through cellular matrices, and growth factor production and release by autocrine cell systems.

Background Chronic fatigue syndrome (CFS) is a debilitating disorder characterized by persistent fatigue that is not alleviated by rest. The lack of a clearly identified underlying mechanism has hindered the development of effective treatments. Studies have demonstrated elevated levels of inflammatory factors in patients with CFS, but findings are contradictory across studies and no biomarkers have been consistently supported. Single time-point approaches potentially overlook important features of CFS, such as fluctuations in fatigue severity. We have observed that individuals with CFS demonstrate significant day-to-day variability in their fatigue severity. Methods Therefore, to complement previous studies, we implemented a novel longitudinal study design to investigate the role of cytokines in CFS pathophysiology. Ten women meeting the Fukuda diagnostic criteria for CFS and ten healthy age- and body mass index (BMI)-matched women underwent 25 consecutive days of blood draws and self-reporting of symptom severity. A 51-plex cytokine panel via Luminex was performed for each of the 500 serum samples collected. Our primary hypothesis was that daily fatigue severity would be significantly correlated with the inflammatory adipokine leptin, in the women with CFS and not in the healthy control women. As a post-hoc analysis, a machine learning algorithm using all 51 cytokines was implemented to determine whether immune factors could distinguish high from low fatigue days. Results Self-reported fatigue severity was significantly correlated with leptin levels in six of the participants with CFS and one healthy control, supporting our primary hypothesis. The machine learning algorithm distinguished high from low fatigue days in the CFS group with 78.3% accuracy. Conclusions Our results support the role of cytokines in the pathophysiology of CFS.

The adhesion of biological cells to substrates is often mediated by binding between cellular receptors andsubstrate-bound ligand. In this work, we used a centrifugation assay to measure the adhesion of rat basophilic leukemia (RBL) cells coated with immunoglobulin E (IgE) to substrates coated with the ligand dinitrophenol (DNP). Increasing force, decreasing DNP substrate density, and decreasing cell surface IgE density all led to decreasing adhesion. Experiments performed at low IgE cell surface densities, in which few tethers from between cell and substrate suggest individual tethers have a binding strength of 2 to 4 microdyne, in agreement with previous measurements of the force to uproot receptors from the plasma membrane

This article provides an overview of the upstream technologies used in the industrial production of therapeutic monoclonal antibodies (mAbs) based on the cultivation of mammalian cells. More specifically, in a first section, after a short discussion of relevant biochemical characteristics of antibodies, we review the cell lines currently employed in commercial production and the methods of constructing and isolating production clones. This is followed with a review of the most current methods of commercial scale production and their associated technologies. Selected references and short discussions pertaining to emerging and relevant technologies have been embedded throughout the text in order to give a sense of the overall direction the field is taking.

Arguments have been made that the culture of nursing homes (NHs) must change to improve the quality of care, and two initiatives have been designed to accomplish this goal. One initiative is to provide resident outcome information (quality indicators) to NH management and consumers via public reporting systems. This initiative is based on the assumptions that resident outcomes are related to care processes implemented by NH staff, the NH industry will respond to market forces, and there are management systems in place within NHs to change the behavior of direct care staff if outcomes are poor. A separate staffing initiative argues that NH care will not improve until there are resources available to increase the number of direct care staff and improve staff training. This initiative also assumes that systems are in place to manage staff resources. Unfortunately, these initiatives may have limited efficacy because information useful for managing the behavior of direct care providers is unavailable within NHs. Medical record documentation about daily care-process implementation may be so erroneous that even the best-intentioned efforts to improve the care received by residents will not be successful. A culture of inaccurate documentation is largely created by a discrepancy between care expectations placed on NHs by regulatory guidelines and inadequate reimbursement to fulfill these expectations. Nursing home staff have little incentive to implement the technologies necessary to audit and assure data quality if accurate documentation reveals that care consistent with regulatory guidelines is not or cannot be provided. A survey process that largely focuses on chart documentation to assess quality provides further incentive for care-process documentation as opposed to care-process delivery. This article reviews methods to improve the accuracy of NH medical record documentation and to create data systems useful for staff training and management.

Objectives The objectives of this study were to describe changes in prescription analgesic and antidepressant medications and to track the costs associated with these medication changes when elderly Medicaid beneficiaries move from the community to a nursing home setting. Design Retrospective analysis of Medicaid long-term care and drugs claims data for fiscal year 2000 from three different states. Setting Long-term care facilities in three different states. Participants We studied 1321 elderly Medicaid beneficiaries newly admitted to a nursing home during the study period. Measurements Pain medications were grouped into four different categories and all antidepressants were grouped into one category. For each medication category, we obtained the number of unique patients for whom it was prescribed, the number of days it was prescribed, and the amount paid by Medicaid. We then calculated the percentage of subjects prescribed and the amount paid per day for each medication class before and after nursing home admission. Results Except for skeletal muscle relaxants, 21% to 39% of beneficiaries already had claims linked to each medication class while still living in the community. After nursing home admission, the percentage of beneficiaries exposed to each medication class increased by 2% to 33%. Cost per day of therapy increased by 10% to 83%. There was significant variation among the states in utilization and cost per day of therapy. Conclusions We draw three major conclusions: (1) community-dwelling elderly Medicaid beneficiaries in this study use more prescription analgesics and antidepressants than community-dwelling elders in prior studies; (2) there is a significant increase in medication utilization and cost on nursing home admission; and (3) significant variability in medication use and cost exists among the three states examined. Further investigation to elucidate the reasons for these differences could assist legislators in formulating sound public policy to contain Medicaid expenditures without sacrificing patient care.

The authors compare the banking crises experienced in Estonia, Latvia, and Lithuania, examining the causes, effects, and policy responses. Estonia and Lithuania reconstituted the specialized Soviet banks as national state banks and began to privatize them. Latvia, by contrast, reconstituted the savings bank, then privatized branches of the remaining banks. In the early stages the three private banking systems were similar and grew rapidly. All three have had liberal policies toward licensing new commercial banks, believing that more banks would generate the competition needed to drive down deposit and lending rates, and provide the capital needed to support the emerging private sector. Little though was given at first to the implications of this policy for banking safety and supervision. The following conclusions, drawn by the authors, may have implications for banking reform in other former Soviet republics, especially the smaller ones: 1) some banking distress is inevitable; 2) banking distress may be desirable; 3) banking crises die down relatively quickly; 4) when crises arise, authorities should respond firmly and promptly; 5) corruption and weakness should never be rewarded; 6) banking crises should be prepared for; and 7) supervisors should send strong signals to bankers about appropriate banking behavior.

The authors compare the banking crises experienced in Estonia, Latvia, and Lithuania, examining the causes, effects, and policy responses. Estonia and Lithuania reconstituted the specialized Soviet banks as national state banks and began to privatize them. Latvia, by contrast, reconstituted the savings bank, then privatized branches of the remaining banks. In the early stages the three private banking systems were similar and grew rapidly. All three have had liberal policies toward licensing new commercial banks, believing that more banks would generate the competition needed to drive down deposit and lending rates, and provide the capital needed to support the emerging private sector. Little though was given at first to the implications of this policy for banking safety and supervision. The following conclusions, drawn by the authors, may have implications for banking reform in other former Soviet republics, especially the smaller ones: 1) some banking distress is inevitable; 2) banking distress may be desirable; 3) banking crises die down relatively quickly; 4) when crises arise, authorities should respond firmly and promptly; 5) corruption and weakness should never be rewarded; 6) banking crises should be prepared for; and 7) supervisors should send strong signals to bankers about appropriate banking behavior.

A common ‘neural integrator’ has been hypothesized to perform mathematical integration of velocity-coded inputs for all oculomotor subsystems. Studies in cats suggested that the integrators for some subsystems may be differentially affected by drugs. Our tests in macaques show that the fixation is unaffected and saccadic and vestibulo-ocular systems are affected in parallel. Thus, the common integrator hypothesis cannot be ruled out on the basis of these results.

The Qa-1b allele is assigned to strains whose peripheral lymphocytes are not lysed by a standard anti-Qa-1 serum. In order to investigate whether Qa-1b represents a single allele or several alleles that have been grouped together as “not a,” we studied the activity of cytotoxic T lymphocytes (CTL) specific for Qa-1b-associated antigens. Cold target inhibition experiments were performed to test the ability of various Qa-1b targets to inhibit the lysis of 51Cr-labeled B10 blasts by B10.BR anti-C3H and C57BR anti-AKR CTL. Qa-1a targets did not inhibit lysis relative to controls syngeneic with the CTL. In contrast, Qa-1b cold targets strongly inhibited the lysis of labeled B10 targets. We found no differences in inhibition among 16 Qa-1b strains representing six H-2 haplotypes and nine different backgrounds. These data indicate that all of these Qa-1b strains express the Qa-1 antigens shared by B10 and C3H or AKR, and thus suggest that Qa-1 is markedly less polymorphic than H-2. Experiments were also performed to test the possibility that Qa-1-associated antigens are involved in the recognition of minor histocompatibility determinants. CTL were generated in secondary cultures between strains identical at Qa-1 and at H-2, but differing at minor histocompatibility loci. These CTL were tested for their ability to lyse targets bearing the minor histocompatibility antigens of the stimulators, and sharing either Qa region or H-2 antigens with the stimulators. In contrast with the well established role for H-2K and H-2D antigens in the recognition of conventional determinants, we found that in both Qa-1a and Qa-1b strain combinations, Qa region homology was neither necessary nor sufficient for minor locus-specific lysis.

We have shown that cytotoxic lymphocytes generated in primary cultures of NZB spleen cells with H-2-identical BALB/c or B10.D2 stimulator cells exhibit specificity for Qa-1b-associated antigenic determinants. This unidirectional cytotoxicity constitutes the initial demonstration of a primary in vitro response to antigens of the Qa-Tla system. Such responses do not require H-2 homology between effector and target cells in the assay system. In fact, when H-2Dd homologous target cells were employed there was little, if any, evidence for development of primary H-2-restricted responses to minor locus histocompatibility antigens or viral antigens. In view of the recently defined role of Qa-1+, Ly-1,2,3+ cells as regulators of antibody responses, and of the deficiency of such cells in NZB mice, the observation of hyperreactivity for determinants of this system may be relevant to the development of autoimmunity in these animals.