Beyond specialist programmes: a study of the needs of offenders with intellectual disability requiring psychiatric attention.

BACKGROUND: Despite the increased prevalence of psychiatric disorder amongst offenders with an intellectual disability (ID), there is very little known about the characteristics and needs of those with dual disability. METHOD: A study of admissions to a new community forensic dual disability clinic during the first 10 months of its operation. RESULTS: Typically, the offenders are male, are older than other offenders, exhibit long-standing and continuing serious behavioural disturbance (independent of their psychiatric diagnosis or level of involvement with the criminal justice system) and require supported or custodial accommodation, despite only mild or borderline levels of ID. Although only one-third have a diagnosable major nonparaphilic psychiatric disorder, three-quarters have had prior or current contact with psychiatric services and two-thirds suffer chronic medical illness. CONCLUSIONS: These offenders suffer psychosocial disadvantages far more extensive than those implied by the "psychiatric" or "disability" label. The multiple services provided to this group have been ad hoc, poorly co-ordinated and sometimes dangerously inappropriate. A service provision model is required which must be integrative and consistent. We suggest the use of multiskilled key workers, who maintain close contact with individual clients. Their role will be to implement management plans from the various specialist agencies who become involved with this group and provide long-term follow-up of their recommendations.

Foot-and-mouth disease virus leader proteinase: involvement of C-terminal residues in self-processing and cleavage of eIF4GI.

The leader proteinase (L(pro)) of foot-and-mouth disease virus frees itself from the nascent polyprotein, cleaving between its own C terminus and the N terminus of VP4 at the sequence Lys-Leu-Lys- downward arrow-Gly-Ala-Gly. Subsequently, the L(pro) impairs protein synthesis from capped mRNAs in the infected cell by processing a host protein, eukaryotic initiation factor 4GI, at the sequence Asn-Leu-Gly- downward arrow-Arg-Thr-Thr. A rabbit reticulocyte lysate system was used to examine the substrate specificity of L(pro) and the relationship of the two cleavage reactions. We show that L(pro) requires a basic residue at one side of the scissile bond to carry out efficient self-processing. This reaction is abrogated when leucine and lysine prior to the cleavage site are substituted by serine and glutamine, respectively. However, the cleavage of eIF4GI is unaffected by the inhibition of self-processing. Removal of the 18-amino acid C-terminal extension of L(pro) slowed eIF4GI cleavage; replacement of the C-terminal extension by unrelated amino acid sequences further delayed this cleavage. Surprisingly, wild-type L(pro) and the C-terminal variants all processed the polyprotein cleavage site in an intermolecular reaction at the same rate. However, when the polyprotein cleavage site was part of the same polypeptide chain as the wild-type Lb(pro), the rate of processing was much more rapid. These experiments strongly suggest that self-processing is an intramolecular reaction.

Extremely efficient cleavage of eIF4G by picornaviral proteinases L and 2A in vitro.

Certain picornaviruses encode proteinases which cleave the translation initiation factor eIF4G, a member of the eIF4F complex which recruits mRNA to the 40S ribosomal subunit during initiation of protein synthesis in eukaryotes. We have compared the efficiency of eIF4G cleavage in rabbit reticulocyte lysates during translation of mRNAs encoding the foot-and-mouth disease virus leader proteinase (Lpro) or the human rhinovirus 2Apro. Under standard translation conditions, Lpro cleaved 50% of eIF4G within 4 min after initiation of protein synthesis, whereas 2Apro required 15 min. At these times, the molar ratios of proteinase to eIF4G were 1:130 for Lpro and 1:12 for 2Apro, indicating a much more efficient in vitro cleavage than previously observed. The molar ratios are similar to those observed during viral infection in vivo.

Structural and biochemical features distinguish the foot-and-mouth disease virus leader proteinase from other papain-like enzymes.

The structures of the two leader protease (Lpro) variants of foot-and-mouth disease virus known to date were solved using crystals in which molecules were organized as molecular fibers. Such crystals diffract to a resolution of only approximately 3 A. This singular, pseudo-polymeric organization is present in a new Lpro crystal form showing a cubic packing. As molecular fiber formation appeared unrelated to crystallization conditions, we mutated the reactive cysteine 133 residue, which makes a disulfide bridge between adjacent monomers in the fibers, to serine. None of the intermolecular contacts found in the molecular fibers was present in crystals of this variant. Analysis of this Lpro structure, refined at 1.9 A resolution, enables a detailed definition of the active center of the enzyme, including the solvent organization. Assay of Lpro activity on a fluorescent hexapeptide substrate showed that Lpro, in contrast to papain, was highly sensitive to increases in the cation concentration and was active only across a narrow pH range. Examination of the Lpro structure revealed that three aspartate residues near the active site, not present in papain-like enzymes, are probably responsible for these properties.

Pentavalent treatment: preliminary effects on state hospital utilization.

The purpose of this exploratory study was to determine if a low-cost alternative to assertive community treatment (ACT) programs could achieve results comparable to those previously reported by high-fidelity ACT programs with regard to state hospital utilization by patients with long-term, treatment-refractory serious mental illness and high rates of hospital recidivism. A sample of 30 patients was exposed to a low- cost alternative to ACT for a 12-month period. A quasi-experimental research design was used to compare state hospital utilization by the treatment group and a matched comparison group. The treatment group exhibited significantly less state hospital utilization than the comparison group and had an 88% reduction in state hospital utilization in comparison to its 10-year baseline. Low cost alternatives to ACT programs may be as effective as high-fidelity programs in reducing state hospital utilization and may be more easily adaptable to the current structure, operation, and financial constraints of community mental health centers.

MP2C, a plant protein phosphatase 2C, functions as a negative regulator of mitogen-activated protein kinase pathways in yeast and plants.

By interference of the yeast pheromone mitogen-activated protein kinase (MAPK) pathway with an alfalfa cDNA expression library, we have isolated the MP2C gene encoding a functional protein phosphatase type 2C. Epistasis analysis in yeast indicated that the molecular target of the MP2C phosphatase is Ste11, a MAPK kinase kinase that is a central regulator of the pheromone and osmosensing pathways. In plants, MP2C functions as a negative regulator of the stress-activated MAPK (SAMK) pathway that is activated by cold, drought, touch, and wounding. Although activation of the SAMK pathway occurs by a posttranslational mechanism, de novo transcription and translation of protein factor(s) are necessary for its inactivation. MP2C is likely to be this or one of these factors, because wound-induced activation of SAMK is followed by MP2C gene expression and recombinant glutathione S-transferase-MP2C is able to inactivate extracts containing wound-induced SAMK. Wound-induced MP2C expression is a transient event and correlates with the refractory period, i.e., the time when restimulation of the SAMK pathway is not possible by a second stimulation. These data suggest that MP2C is part of a negative feedback mechanism that is responsible for resetting the SAMK cascade in plants.

Doctors and public authorities: the trend toward collaboration.

Insuring a population and managing its money require a comprehensive health care financing system. Many issues must be resolved, particularly the roles of the medical profession and its relationship with organizations of laymen in insurance carriers and in government. The spread of society-wide, third-party reimbursement produced conflicts with doctors over admission to practice, work rules, and pay in all countries. Eventually new arrangements were made to settle conflicts of interest and to ensure the harmonious operation of health care services. Policymakers and financial managers came to realize that the medical profession as a whole must be motivated to ensure the success of the system. Recently countries with statutory health insurance and direct public financing created new systems for negotiation and for joint decision making. Even some governments now agree to collaborate with doctors as virtual peers rather than to dictate rules and finance. The only exception is the United States, which will continue to have periodic conflicts until it crafts a joint decision-making system. The evidence comes from the author's first-hand field research over thirty years in the principal developed countries in Europe and North America. He interviewed informants, collected reports, and observed events for these topics primarily in Germany, France, the Netherlands, Great Britain, Canada, and the United States.

The United States needs a health system like other countries.

Every developed country except the United States has a comprehensive health system for coverage, service provision, and finance. Social policy in the United States once was guided by thinkers who realized this, and the Social Security system--complete except for health insurance--resulted. The climate of thinking changed, and health policy for some time has been dominated by classical economists who argue that free competitive markets will solve all problems. They justify their arguments by claiming that the only alternative is full government takeovers of service and financing, as in Canada. While this debate has dragged along, problems in the United States have become grave. Instead of reviving the institutional economics and social policies that once served the United States well, the Clinton administration has turned policy over to devotees of managed competition. But the problem is how to organize the country, and national health insurance--easily observed in other countries--is superior to the current chaos and free-market utopias in the United States. Important aims would be achieved, such as expanding coverage, obtaining stable revenue, and containing costs. Important political barriers can be overcome, such as resistance by small business. Such a health system includes machinery for setting goals and implementing results, involving collaboration among providers, payers, and government.

The competition vogue and its outcomes.

Social security and comprehensive health care financing were developed to protect all citizens and to redistribute money to cover costs. Their inspiration was social solidarity rather than pecuniary self-interest. The United States differed from other countries by continuing a private market in health, with many self-centred and competing providers and insurers; and its prevailing school of health economics deplored the national health insurance and national health services that were universal in other countries and recommended devices that would eliminate "market failure" in health. When health economics grew in Europe during the 1970s and 1980s, the reformers' first presumption was that the voluminous American market-oriented literature must offer answers; but much of it proved superfluous, since European health care systems still had much competition and consumer choice, and they worked better than the reality in the United States. The United States itself has paid a heavy price for turning over health financing policy to the devotees of microeconomics and free markets, and today its serious problems in health are unsolved. So powerful is the pro-competitive ideology that it has now been adopted by the Democratic Clinton Administration, contradicting the heritage of Roosevelt, Truman, and Johnson.

Universal health insurance that really works: foreign lessons for the United States.

The United States has serious and worsening problems in the delivery and financing of health. The debate about reform has inspired many schemes that are persuasive in their presentation, but they are unrealistic: some cannot be enacted by Congress, others would not improve existing arrangements, most are imaginary inventions with uncertain outcomes. The most politically prudent and the most effective course is to emulate the methods used successfully and available for full analysis in other developed countries. America created its successful social security system in this fashion, and statutory health insurance should be added now. All or most groups would be required to join. Financing would come from social security payroll taxes, supplemented by government subsidies. Basic acute care services would be equally available to all. The existing insurance companies would remain as fiscal intermediaries. Doctors and hospitals would continue to work much as they do now. They would prosper from more utilization, few bad debts, and less administrative trouble. The payment and work of doctors would be governed by collective negotiations between the insurance carriers and the medical associations. The payment and work of hospitals would be governed by a mixture of government regulations and negotiations with the carriers. Costs would be controlled by coordinated decision making by the payers, the providers, and government. The system would not turn over services and financing to government.

How expenditure caps and expenditure targets really work.

Every organized payment system must contain its costs in order to keep within revenue without denying benefits. Fixed expenditure caps requiring the provider to operate within its annual financial grant can be imposed on organizations like hospitals, but are fiercely resisted by the medical profession. All financial arrangements with doctors are negotiated, including systems of fixed expenditure caps and more flexible expenditure targets. If the doctors accept the principle of caps and cooperate in achieving them, they do so only as part of a negotiated settlement to avoid a worse outcome. Government's power is minimized, even when government is the payer. Caps on the physicians' sector are unusual. Instead, we see the spread of flexible targeting systems, wherein cost overruns are compensated for by lower expenditure targets the following year. Medical associations in all countries resisted even these restraints for years, but eventually accepted them, provided that target setting, judgments of overruns, utilization control, and all other features are part of a joint negotiating system. Targeting systems are often complicated because they preserve the semiprivate character of statutory health insurance and they are the result of negotiated compromises. To succeed in controlling costs, they require the cooperation of the medical association and of the rank-and-file doctors--but they can succeed. The United States has enacted a small-scale targeting system for Medicare physician payments alone. It cannot become the method for universal health insurance, which must heed lessons from abroad. Only an all-payer system can cover an entire population and contain the costs of the system. A few government officials cannot dictate and implement expenditure goals, but a system of consultation is required for setting and carrying out targets. Impartial officials can regulate hospitals according to the guidelines produced by the consultations, but the record of the medical profession in the countries reviewed here is that they insist on negotiating the final rules and rates. Americans have become bewitched by the mirage of econometric formulas automatically governing a sector, but the real problem is to devise and operate a harmonious decision-making system.

Picture naming.

Picture naming has become an important experimental paradigm in cognitive psychology. To name a picture can be considered an elementary process in the use of language. Thus, its chronometric analysis elucidates cognitive structures and processes that underlie speaking. Essentially, these analyses compare picture naming with reading, picture categorizing, and word categorizing. Furthermore, techniques of double stimulation such as the paradigms of priming and of Stroop-like interference are used. In this article, recent results obtained with these methods are reviewed and discussed with regard to five hypotheses about the cognitive structures that are involved in picture naming. Beside the older hypotheses of internal coding systems with only verbal or only pictorial format, the hypotheses of an internal dual code with a pictorial and a verbal component, of a common abstract code with logogen and pictogen subsystems, and the so-called lexical hypothesis are discussed. The latter postulates two main components: an abstract semantic memory which, nevertheless, also subserves picture processing, and a lexicon that carries out the huge amount of word processing without semantic interpretation that is necessary in hearing, reading, speaking and writing.

Paying the hospital: American problems and foreign solutions.

Hospital financing in the United States suffers from many problems. Many persons lack access because they lack third-party coverage. Among those covered, benefits vary, and persons receive unequal services. Costs are high and are uncontrolled. The hospital is burdened by complicated relations with many payers. In order to cover their costs and earn extra cash, hospitals overcharge the more generous third parties, and recriminations result. All other developed countries have either statutory health insurance, national health services, or full public financing of privately managed hospitals. Whatever the financing method, all countries avoid the problems prevailing in the United States. All citizens are covered, all have access, and hospitals reject no one for financial reasons. All citizens have equal benefits and receive the same basic services. Regulation by government and negotiations with health insurance carriers guarantee the hospital's operating costs to service its catchment area adequately, but also prevent the hospital from installing excessive equipment and excessive staff. Each hospital is paid by all-payer standard rates, administration of reimbursement is simple, and shifting of costs among payers is both unnecessary and administratively impossible. Costs are contained by the total management of the system, not by fragmented efforts by separate insurance carriers. Considerable strategic thinking by government, the providers, and other interest groups sets guidelines for spending levels every year to meet the country's clinical needs but also to stay within its fiscal capacity. Capital investment for new treatments depends on government grants and evaluation of needs.

Designing fee schedules by formulae, politics, and negotiations.

Fee-for-service cannot be used successfully by organized health insurance without a fee schedule. America first tried to pay doctors under Medicare by an involved formula system without a fee schedule, but the effort has failed. The United States has now commissioned a research project to design a unique fee schedule that will precisely reflect physicians' effort and practice costs and that will represent the prices produced by a perfectly competitively market. The primary goal is the same as that pursued recently by reformers in all countries: viz., narrow the spread in fees and income between surgical and cognitive fields. There are serious technical limitations on this effort, despite the talent of the research team. An additional difficulty lies in the nature of the subject: paying the doctor involves conflicts of interest between payers and all doctors as well as among the medical specialties, and the conflicts cannot be resolved by any formulae calculated by any single research team. Methodological and political compromises will be necessary, in order to adopt a reform. The new method may be just as politically driven, complicated, and disputed as the old one, despite America's pretenses that it prefers free markets and opposes excessive government.