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The problem of efficiency vs fairness is considered in relation to the splitting of costs for shared facilities between users. This is considered as a result of a problem of sharing the cost of the provision of central computing facilities between different faculties in a large university, but the basic problem is widespread. A linear programming model is considered in order to minimise cost. The dual of this model is shown to correspond to an efficient allocation of costs. An alternative optimal dual solution is shown to give a `fair' solution according to criteria resulting from cooperative game theory. Journal of the Operational Research Society (2002) 53, 1324-1329. doi: 10.1057/palgrave.jors.2601456 Keywords: cost allocation; efficiency; fairness; linear programming; duality; game theory

Global neurosurgery seeks to provide quality neurosurgical health care worldwide and faces challenges because of historical, socioeconomic, and political factors. To address the shortfall of essential neurosurgical procedures worldwide, dyads between established neurosurgical and developing centers have been established. Concerns have been raised about their effectiveness and ability to sustain capacity development. Successful partnerships involve multiple stakeholders, extended timelines, and twinning programs. This article outlines current initiatives and challenges within the neurosurgical community. This narrative review aims to provide a practical tool for colleagues embarking on clinical partnerships, the Engagements and assets, Capacity, Operative autonomy, Sustainability, and scalability (ECOSystem) of care. To create the ECOSystem of care in global neurosurgery, the authors had multiple online discussions regarding important points in the practical tool. All developed tiers were expanded based on logistics, clinical, and educational aspects. An online search was performed from August to November 2023 to highlight global neurosurgery partnerships and link them to tiers of the ECOSystem. The ECOSystem of care involves 5 tiers: Tiers 0 (foundation), 1 (essential), 2 (complexity), 3 (autonomy), and 4 (final). A nonexhaustive list of 16 neurosurgical partnerships was created and serves as a reference for using the ECOSystem. Personal experiences from the authors through their partnerships were also captured. We propose a tiered approach for capacity building that provides structured guidance for establishing neurosurgical partnerships with the ECOSystem of care. Clinical partnerships in global neurosurgery aim to build autonomy, enabling independent provision of quality healthcare services., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: One strategy to increase the availability of neurosurgical services in underserved regions within Sub-Saharan African countries is to create new residency training programs outside of cosmopolitan cities where programs may already exist. In 2016 Tenwek Hospital in rural western Kenya began offering full-time neurosurgical services and in 2020 inaugurated a residency training program. This review highlights the operative epidemiology of the first 5 years of the hospital's neurosurgical department., Methods: A retrospective review of all cases performed by a neurosurgeon at Tenwek Hospital between September 2016 and February 2022 was performed. Patient demographics, surgical indications, length of stay, and in-hospital mortality rates were collected., Results: A total of 1756 cases were retrievable. Of these, 1006 (57.3%) were male and mean age was 30 years (range 1 day to 97 years). Mean length of stay was 11 ± 2 days and in-hospital mortality rate was 4.4% (77 patients). The most common pathologies in children comprised hydrocephalus and spina bifida (42.5% and 21.1%, respectively); in adults, cranial trauma (28.2%), oncology (25.2%), and degenerative spine (18.5%) were most common. Trauma was the leading cause of death., Conclusions: The neurosurgical caseload of a rural hospital in an underserved area can provide not only an adequate neurosurgical volume, but a robust and varied exposure that is necessary for training safe and competent surgeons who are willing to remain in their countries of origin., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Acromegaly has high morbidity and mortality when growth hormone secretion remains uncontrolled. Stereotactic radiosurgery (SRS) may be used when pituitary surgery is not suitable or unsuccessful, but there are few very long-term safety data available, especially for significant adverse events such as stroke., Methods: 118 patients with acromegaly were treated with SRS between 1985 and 2015, at the National Centre for Stereotactic Radiosurgery, Sheffield, UK. Data were gathered from case notes, hospital databases, and patient questionnaires. Stroke incidence in comparison to the normal population was quantified using the standardised incidence ratio (SIR), and visual complications assessed., Results: 88% (104/118) had complete morbidity follow up data for analysis. The mean follow-up was 134 months, and median SRS dose was 30 Gy. 81% of tumours had cavernous sinus invasion. There was no excess stroke rate relative to that seen in two age- and sex-matched large population studies (SIR = 1.36, 95% CI 0.27-3.96; SIR = 0.52, 95% CI 0.06-1.89). In 68/104 patients who had MRI-guided SRS with no further radiation treatment (SRS or fractionated radiotherapy) there was no loss of visual acuity and 3% developed ophthalmoplegia. There was a positive correlation between > 1 radiation treatment and both ophthalmoplegia and worsening visual acuity., Conclusion: Stroke rate is not increased by SRS for acromegaly. Accurate MRI-based treatment planning and single SRS treatment allow the lowest complication rates. More than one radiation treatment (SRS or fractionated radiotherapy) was associated with increased visual complications., (© 2021. The Author(s).)

As policymakers and school communities work to address underlying causes of achievement gaps and access to quality early childhood education, this study considers the use of 21st Century Community Learning Centers to address early childhood education needs on western U.S. state, Idaho. The study sought to understand the relationship between federal and state policies related to out-of-school opportunities to enhance early childhood education. Utilizing data from a statewide evaluation of Idaho's 21st Century Learning Centers, the study examined 92 centers providing after school, before school, or summer programs in grades preschool through the third grade to predominately at-risk children. Data collection included quantitative data from a survey given to parents ( n  = 183), as well as qualitative data collected through site-based interviews, focus groups and observations. Data included a review of historical and current data on participation rates; attendance rates; standardized test scores for program participants in grades PK-3 ( n  = 3258). Data were analyzed for themes and transfer. The study findings provide further insight into understanding possible relationships between U.S. federal and state policy regarding 21st Century Community Learning Centers on both students' outcomes and parent satisfaction. The findings further support the role of out-of-school time (OST) experiences in the larger ecosystem of learning and provides insight into understanding how the OST activities are carried over into family life., Competing Interests: Competing interestsThe author declares no competing interests., (© The Author(s) 2021.)

Objective: Transsphenoidal surgery (TSS) remains the recommended primary treatment for acromegaly. Long-term outcome data are not available for patients treated with gamma knife radiosurgery (STRS) as a primary treatment., Design: Retrospective cohort study., Data Collection: notes review, laboratory results, general physician notes, patient questionnaire and death certification., Patients: Twenty acromegaly patients underwent primary STRS at the National Centre for Radiosurgery, Sheffield, UK, between 1985 and 2015., Measurements: Biochemical control (GH/IGF1), hypopituitarism, morbidity and mortality were all recorded., Results: At 20 years of follow-up, control was seen in all on acromegaly-specific medication (n = 12) and 75% of those off medication (3/4). Time for 50% to achieve control on medication was 3 years, and 7.4 years off medication. Median marginal radiation dose was 27.5 Gy, and median follow-up was 166.5 months. 53% of patients developed new hypopituitarism at a median follow-up of 146 months, and the development of first onset of hypopituitarism occurred as late as 20 years after treatment. With MRI planning, no other complications were noted. Three patients underwent subsequent TSS due to poor biochemical control. During follow-up, 7 patients died at a median age of 65 years. There were no STRS-related deaths., Conclusion: This is the longest follow-up of patients who have undergone primary STRS for acromegaly. It shows low morbidity, but significant latency to biochemical control and new-onset hypopituitarism. This mandates very long-term follow-up for these patients. STRS has shown good long-term efficacy providing initial control can be afforded by optimal medical management. While TSS remains best practice, STRS offers an alternative for those in whom surgery is not an option., (© 2018 Crown copyright. Clinical Endocrinology © 2018 John Wiley & Sons Ltd.)

Background: Out-of-school time (OST) programs are an important setting for supporting student health and academic achievement. This study describes the prevalence and characteristics of school-based OST programs, which can inform efforts to promote healthy behaviors in this setting., Methods: A nationally representative sample of public elementary schools (N = 640) completed surveys in 2013-2014. Administrators reported on OST programs and policies at their school. Multivariable logistic regression models estimated the prevalence of school-based OST programs, adjusting for school characteristics. Among schools with OST programs (N = 475), chi-square tests identified school characteristics associated with having an OST policy about physical activity or nutrition., Results: Three fourths of elementary schools (75.6%) had a full- or partial-year school-based OST program, with 30.8% having both. Full- and partial-year programs were significantly less prevalent in rural and township areas versus urban settings. Only 27.5% of schools with OST programs reported having physical activity and/or nutrition policies., Conclusions: Most US elementary schools have an on-site OST program, but disparities in access exist, and most lack policies or awareness of existing policies regarding physical activity and nutrition. To maximize OST programs' potential benefits, strategies are needed to increase access to programs and physical activity and/or nutrition policy adoption., (© 2018, American School Health Association.)

Background: To describe the extent of renal disease in Ugandan children surviving at least ten years after spina bifida repair and to investigate risk factors for renal deterioration in this cohort., Patients and Methods: Children who had undergone spina bifida repair at CURE Children's Hospital of Uganda between 2000 and 2004 were invited to attend interview, physical examination, renal tract ultrasound, and a blood test (creatinine). Medical records were retrospectively reviewed. The following were considered evidence of renal damage: elevated creatinine, hypertension, and ultrasound findings of hydronephrosis, scarring, and discrepancy in renal size >1cm. Female sex, previous UTI, neurological level, mobility, detrusor leak point pressure, and adherence with clean intermittent catheterisation (CIC) were investigated for association with evidence of renal damage., Results: 65 of 68 children aged 10-14 completed the assessment. The majority (83%) reported incontinence. 17 children (26%) were performing CIC. One child had elevated creatinine. 25 children (38%) were hypertensive. There was a high prevalence of ultrasound abnormalities: hydronephrosis in 10 children (15%), scarring in 42 (64%), and >1cm size discrepancy in 28 (43%). No children with lesions at S1 or below had hydronephrosis (p = 0.025), but this group had comparable prevalence of renal size discrepancy, scarring, and hypertension to those children with higher lesions., Conclusions: Incontinence, ultrasound abnormalities, and hypertension are highly prevalent in a cohort of Ugandan children with spina bifida, including those with low neurological lesions. These findings support the early and universal initiation of CIC with anticholinergic therapy in a low-income setting.

Background: Children surviving after spina bifida repair often have significant disability, the consequences of which may be more profound in low-income countries. The aim of this cross-sectional study was to measure quality of life (QOL) reported by children with spina bifida in Uganda, and to define factors associated with QOL., Methods: QOL was measured using both the Health Utilities Index (HUI3) Tool and a visual analogue scale (VAS) marked from 0 to 10. In keeping with the WHO definition of QOL, further analysis was conducted using subjective QOL scores (using the VAS). Multivariate regression was used to investigate the association between VAS scores and prespecified variables: age, sex, hydrocephalus, mobility, urinary continence, school attendance and family size., Results: Sixty two of 68 surviving children aged 10-14 were able to complete all aspects of the assessment. There was poor correlation between the VAS and HUI3 Tool (Pearson correlation 0.488). On multivariate regression, the following variables were associated with a significant change in the 10-point VAS (change in score; 95% CI): male sex (-1.45; -2.436 to -0.465), urinary continence (1.681; 0.190 to 3.172), large family size (-1.775; -2.773 to -0.777) and hydrocephalus (-1.382; -2.374 to -0.465)., Conclusions: Urinary continence and family size are potentially modifiable, the former by simple and inexpensive medical management. Enhanced investment in community-based rehabilitation and support is urgently needed. Delivery of family planning services is a national priority in Uganda, and should be discussed with families as part of holistic care., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Human immunodeficiency virus (HIV) is a global health problem. It renders the central nervous system susceptible to infectious and noninfectious diseases. HIV-positive individuals may present to neurosurgical services with brain lesions of unknown etiology. The differential diagnosis in these cases is broad, including opportunistic infections and malignancies, and investigation should be tailored accordingly. Opportunistic infections of the central nervous system can be complicated by hydrocephalus, and the management is pathogen dependent. Patients may also present to a neurosurgical service with conditions unrelated to their HIV status. This review outlines important conditions that cause brain lesions and hydrocephalus. It addresses the issues of diagnosis and intervention in HIV-positive patients in the era of combination antiretroviral therapy, while not ignoring the potential for opportunistic central nervous system infection in undiagnosed patients. The care of HIV-positive patients presenting to neurosurgical services requires a multidisciplinary approach, which is reflected in the authorship of this review, as well as in the guidance given.

Deep Brain Stimulation (DBS) has been used to target many deep brain structures for the treatment of chronic pain. The periaqueductal grey and periventricular grey (PAG/PVG) is an effective target but results are variable, sometimes short-lived or subject to tolerance. The centromedian intra-laminar parafascicular complex (CMPf) modulates medial pain pathways and CMPf DBS may address the affective aspects of pain perception. Stimulation of multiple deep brain targets may offer a strategy to optimize management of patients with complex pain symptomatology. However, previous attempts to stimulate multiple targets requires multiple trajectories and considerable expense. Using a single electrode to stimulate multiple targets would help overcome these challenges. A pre-requisite of such a technique is the ability to use different stimulation parameters at different contacts simultaneously on the same electrode. We describe a novel technique in 3 patients with chronic pain syndromes for whom conventional medical and/or neuromodulation therapy had failed using a single electrode technique to stimulate PVG/PAG and CMPf at dual frequencies., Competing Interests: N.K.P. has been medical advisor to Boston Scientific and has held consultancies to Medtronic, St Jude Medical (now Abbott) and Nevro; he is the chief medical officer at Bioinduction Ltd. (Bristol, United Kingdom). N.B. is a clinical consultant for Renishaw (Gloucestershire, PLC). H.S.-W, A.P. and M.H. declare no conflicts of interest.

OBJECTIVE Myelomeningocele (MM) is a neural tube defect complicated by neurological deficits below the level of the spinal lesion and, in many cases, hydrocephalus. Long-term survival of infants treated for MM in a low- and middle-income country has never been reported. This retrospective cohort study reports 10-year outcomes and factors affecting survival for infants undergoing MM repair at CURE Children's Hospital of Uganda. METHODS Patients were traced by telephone or home visit. Survival was estimated using the Kaplan-Meier method. Multivariate survival was analyzed using the Cox proportional hazards model, investigating the following variables: sex, age at surgery, weight-for-age at surgery, motor level, and presence and management of hydrocephalus. RESULTS A total of 145 children underwent MM repair between 2000 and 2004; complete data were available for 133 patients. The probability of 10-year survival was 55%, with 78% of deaths occurring in the first 5 years. Most of the deaths were not directly related to MM; infection and neglect were most commonly described. Lesions at motor level L-2 or above were associated with increased mortality (HR 3.176, 95% CI 1.557-6.476). Compared with repair within 48 hours of birth, surgery at 15-29 days was associated with increased mortality (HR 9.091, 95% CI 1.169-70.698). CONCLUSIONS Infants in low- and middle-income countries with MM can have long-term survival with basic surgical intervention. Motor level and age at surgery were significant factors influencing outcome. Education of local health care workers and families to ensure both urgent referral for initial treatment and subsequent access to basic medical care are essential to survival.

Background: Several deep brain stimulation (DBS) targets have been explored for the alleviation of trigeminal anaesthesia dolorosa. We aimed to characterise the analgesia produced from the periaqueductal grey (PAG) and centromedian-parafascicular (CmPf) nucleus using a within-subject design., Method: We report a case series of 3 subjects implanted with PAG and CmPf DBS systems for the treatment of anaesthesia dolorosa. At follow-up, testing of onset and offset times, magnitude, and thermal and mechanical sensitivity was performed., Results: The mean pain score of the cohort was acutely reduced by 56% (p < 0.05) with PAG and 67% (p < 0.01) with CmPf stimulation at mean time intervals of 38 and 16 min, respectively. The onset time was 12.5 min (p < 0.05) for PAG stimulation and 2.5 min (p < 0.01) for CmPf. The offset time was 2.5 min (p < 0.05) for PAG and 12.5 min (p < 0.01) for CmPf. The two targets were effective at different stimulation frequencies and were not antagonistic in effect., Conclusion: The mechanisms by which stimulation at these two targets produces analgesia are likely to be different. Certain pain qualities may respond more favourably to specific targets. Knowledge of onset and offset times for the targets can guide optimisation of stimulation settings. The use of more than one stimulation target may be beneficial and should be considered in anaesthesia dolorosa patients., (© 2016 The Author(s) Published by S. Karger AG, Basel.)

A young man with Fisher grade IV subarachnoid haemorrhage (SAH) underwent aneurysm coiling following external ventriculostomy. Coiling was complicated by thrombus formation and parent vessel occlusion necessitating anti-platelet therapy. Several hours after anti-platelet therapy, catastrophic haemorrhage associated with the ventriculostomy tract occurred. Timing and location of haemorrhage suggest combined anti-platelet therapy and ventriculostomy may have been causal. The literature on ventriculostomy haemorrhage rates and risks with concomitant anti-platelet therapy are reviewed. Where endovascular coiling is being considered, the possibility of ventriculostomy-related haemorrhage should be considered and should influence subsequent treatment decisions.

Male Anopheles mosquitoes coagulate their seminal fluids via cross-linking of a substrate, called Plugin, by the seminal transglutaminase AgTG3. Formation of the "mating plug" by cross-linking Plugin is necessary for efficient sperm storage by females. AgTG3 has a similar degree of sequence identity (~30%) to both human Factor XIII (FXIII) and tissue transglutaminase 2 (hTG2). Here we report the solution structure and in vitro activity for the cross-linking reaction of AgTG3 and Plugin. AgTG3 is a dimer in solution and exhibits Ca(2+)-dependent nonproteolytic activation analogous to cytoplasmic FXIII. The C-terminal domain of Plugin is predominantly α-helical with extended tertiary structure and oligomerizes in solution. The specific activity of AgTG3 was measured as 4.25 × 10(-2) units mg(-1). AgTG3 is less active than hTG2 assayed using the general substrate TVQQEL but has 8-10× higher relative activity when Plugin is the substrate. Mass spectrometric analysis of cross-linked Plugin detects specific peptides including a predicted consensus motif for cross-linking by AgTG3. These results support the development of AgTG3 inhibitors as specific and effective chemosterilants for A. gambiae.

Mutations in the lamin A/C (LMNA) gene cause significant disruption to skeletal and myocardial muscle, as well as nervous tissue. We describe a case illustrating varied manifestations of a LMNA mutation and the implications for diagnosis and management. We turn to several family studies that describe considerable phenotypic variation arising from LMNA mutations. The discussion focuses on educating the reader in recognition of potential presentations of LMNA mutations.

Background: In humans, mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system, and clinical phenotypes ranging from Charcot-Marie-Tooth neuropathy to a severe infantile form of spinal muscular atrophy. GARS is ubiquitously expressed and may have functions in addition to its canonical role in protein synthesis through catalyzing the addition of glycine to cognate tRNAs., Methodology/principal Findings: We have recently described a new mouse model with a point mutation in the Gars gene resulting in a cysteine to arginine change at residue 201. Heterozygous Gars(C201R/+) mice have locomotor and sensory deficits. In an investigation of genetic mutations that lead to death of motor and sensory neurons, we have crossed the Gars(C201R/+) mice to two other mutants: the TgSOD1(G93A) model of human amyotrophic lateral sclerosis and the Legs at odd angles mouse (Dync1h1(Loa)) which has a defect in the heavy chain of the dynein complex. We found the Dync1h1(Loa/+);Gars(C201R/+) double heterozygous mice are more impaired than either parent, and this is may be an additive effect of both mutations. Surprisingly, the Gars(C201R) mutation significantly delayed disease onset in the SOD1(G93A);Gars(C201R/+) double heterozygous mutant mice and increased lifespan by 29% on the genetic background investigated., Conclusions/significance: These findings raise intriguing possibilities for the study of pathogenetic mechanisms in all three mouse mutant strains.

Mutations in the enzyme glycyl-tRNA synthetase (GARS) cause motor and sensory axon loss in the peripheral nervous system in humans, described clinically as Charcot-Marie-Tooth type 2D or distal spinal muscular atrophy type V. Here, we characterise a new mouse mutant, Gars(C201R), with a point mutation that leads to a non-conservative substitution within GARS. Heterozygous mice with a C3H genetic background have loss of grip strength, decreased motor flexibility and disruption of fine motor control; this relatively mild phenotype is more severe on a C57BL/6 background. Homozygous mutants have a highly deleterious set of features, including movement difficulties and death before weaning. Heterozygous animals have a reduction in axon diameter in peripheral nerves, slowing of nerve conduction and an alteration in the recovery cycle of myelinated axons, as well as innervation defects. An assessment of GARS levels showed increased protein in 15-day-old mice compared with controls; however, this increase was not observed in 3-month-old animals, indicating that GARS function may be more crucial in younger animals. We found that enzyme activity was not reduced detectably in heterozygotes at any age, but was diminished greatly in homozygous mice compared with controls; thus, homozygous animals may suffer from a partial loss of function. The Gars(C201R) mutation described here is a contribution to our understanding of the mechanism by which mutations in tRNA synthetases, which are fundamentally important, ubiquitously expressed enzymes, cause axonopathy in specific sets of neurons.

Cell polarity is essential for unicellular and multicellular stages of Dictyostelium development. Chemotaxis during early development requires each cell to rapidly reorganize its cytoskeleton to point towards a source of cAMP. This involves a balance between local induction of F-actin polymerization and suppression of pseudopods that point in other directions. Both the lipid phosphatidylinositol (3,4,5) trisphosphate and the soluble signal cGMP have been implicated in these processes, in addition to conserved and novel proteins. During later development cells adopt newly discovered, alternative modes of movement and interact through adhesion molecules. Finally, cells polarize secretion to particular regions of their surface.

Sorting nexins (Snxs) are a recently discovered family of conserved hydrophilic cytoplasmic proteins that have been found associated with membranes of the endocytic system and that are implicated in the trafficking of many endosomal membrane proteins, including the epidermal growth factor receptor and transferrin receptor. Snx proteins are partly defined by the presence of a p40 phox homology domain that has recently been shown to bind phosphatidylinositol 3-phosphate. Most Snx proteins also contain a predicted coiled-coils domain in the carboxyl-terminal half of the protein and have been shown to form dimers with other members of the Snx family. The yeast sorting nexins Vps5p and Vps17p form a dimer and are also components of the retromer complex that mediates endosome-to-Golgi transport of the carboxypeptidase Y receptor Vps10p. To functionally define the different domains of the yeast sorting nexins Vps5p and Vps17p, we have generated various truncations to examine the role that the different domains of Vps5p/Vps17p play in their respective functions. Herein, we show that the C-terminal halves of Vps5p and Vps17p, which contain the coiled-coils domains, are necessary and sufficient for their interaction. We have also mapped the retromer assembly domain to the N-terminal half of Vps5p and found that binding of Vps5p by Vps17p synergizes the interaction between Vps5p and other retromer components. Additionally, we have examined which domain(s) of Vps5p is necessary for membrane association.

We report here an in vivo study of kinesin heavy chain (KHC) functions in yeast. We have identified in Schizosaccharomyces pombe a kinesin motor gene, klp3(+), which has the highest homology to the Neurospora crassa KHC. Using indirect immunofluorescence, HA epitope-tagged Klp3 protein is cytoplasmic and appears as one to a few distinct patches that are coincident with microtubules. The klp3 null allele is viable. In klp3 deleted cells, ER, Golgi and mitochondrial distribution appear normal. Mitochondrial distribution in S. pombe is known to be microtubule-associated. We show that latrunculin A does not cause mitochondria to aggregate, suggesting that mitochondrial distribution in fission yeast, unlike budding yeast, is not dependent upon actin-based processes. Neither latrunculin A nor thiabendazole affects ER or Golgi distribution. We also used the vital dye FM4-64 to visualize the internalization of the dye and its transport to vacuoles in fission yeast in the presence and absence of Klp3. We observed no significant difference between the wild-type and Klp3 null cells in either the dynamics of endocytosis or the distribution and fusion of vacuoles. The drug brefeldin A causes Golgi-to-ER recycling in wild-type fission yeast cells. Although recycling of Golgi to ER after brefeldin A treatment occurs in klp3 null cells, recycling is defective and the distribution pattern we see is different from that observed in the wild-type strain. We conclude that Klp3 plays a role in BFA-induced membrane transport. The nucleotide sequence of S. pombe klp3(+) was submitted to GenBank under Accession No. AF154055., (Copyright 2000 John Wiley & Sons, Ltd.)

A study was undertaken to determine if can-opener (CO) or continuous curvilinear capsulorhexis (CCC) anterior lens capsulotomy influences decentration of a two-zone multifocal intraocular lens (IOL). Fifty IOLs (25 with polypropylene haptics and 25 with poly[methyl methacrylate] haptics) were implanted following CO, 42 with poly(methyl methacrylate) haptics, following CCC. The extent and direction of decentration was estimated using a photogeometric technique. The haptic material may influence decentration. Continuous curvilinear capsulorhexis was associated with less decentration than CO (0.36 mm and 0.43 mm, respectively). The difference, however, was not statistically significant.

The time course of cocaine-induced changes in self-stimulation thresholds were used to evaluate cocaine euphoria and dysphoria as a function of the chronicity of drug treatment, dosage level, and the spacing of injections. It was assumed that cocaine-induced decreases in thresholds were indicative of cocaine euphoria, while increases in thresholds reflected rebound dysphoric responses to cocaine administration. Three experiments were performed using self-stimulating rats implanted with ventral tegmental area electrodes. Cocaine's threshold-lowering effects were evident 15 min postinjection (IP) with thresholds returning to baseline by approximately 3.0 h after treatment. Little evidence for cocaine-induced increases in thresholds was observed during periods of chronic cocaine treatment. However, thresholds were slightly elevated upon withdrawal from chronic cocaine treatment in Experiments 2 and 3. No evidence of tolerance or sensitization to cocaine-induced shifts in thresholds was noted with single daily injections, while multiple daily injections produced tolerance to cocaine's threshold-lowering effects. It is concluded that cocaine's ability to enhance brain-stimulation reward is highly reliable and robust, while decreases in brain-stimulation reward associated with chronic cocaine treatment are less reliable and difficult to demonstrate. The possible influence of drug dosage on the induction of cocaine dysphoria and the ability of various self-stimulation procedures to measure dysphoric effects are discussed.

While some investigators have reported that cocaine increases response rates for brain stimulation reward, others have failed to demonstrate this effect. The present study was designed to evaluate the influence of stimulation parameters, dose of cocaine and operant-dependent response requirements on cocaine's ability to alter self-stimulation rates. Self-stimulation rates were collected on a minute by minute basis for 45 min following IP injections of 0, 5, 15 or 30 mg/kg cocaine HCI. All doses were tested using both nose-poking and lever-pressing operants. It was found that mean lever-pressing rates were significantly increased by 5 mg/kg cocaine, while nose-poking rates were significantly increased by 15 and 30 mg/kg cocaine. Further examination of the pattern of results indicated that the cocaine-induced increases in lever-pressing rate were mainly due to an increase in the time spent self-stimulating, whereas increases in nose-poking were mainly due to increases in nose-poking rate/min within self-stimulation bouts. It was hypothesized that 5 mg/kg cocaine increased lever-pressing by producing response perseveration, while the higher doses increased nose-poking mainly due to the compatibility of the nose-poking response topography with cocaine-induced stereotypies.

Self-stimulation thresholds obtained from rate/intensity functions have often been used to measure brain stimulation reward (BSR) under the assumption that these indices are not contaminated by performance factors. However, very few studies have explicitly examined the effect of performance variables on thresholds. The present experiment examined the joint effects of response effort and current intensity on train duration thresholds. Three levels of stimulation current and lever weightings were factorially combined and train duration thresholds (defined as 50% of maximum response rates) were determined for each condition. It was discovered that changes in both current intensity and response effort produced shifts in thresholds, and that these shifts were of approximately equal magnitude. It was concluded that caution must be exercised when interpreting self-stimulation threshold data since, at least under some conditions, both reward (i.e., train duration) and performance (i.e., effort) manipulations produced similar shifts in self-stimulation response functions.

The results of this investigation have shown that PCP persisted in leaf litter and sediments for at least seventeen months following contamination. This persistence provides a potential for continuous contamination of the water column and biological magnification via detritus- and benthic-feeding organisms. An investigation of these factors is presently underway.

We present a retrospective study of fifty patients who developed raised intraocular pressure in association with herpes simplex kerato-uveitis. We consider the incidence, clinical features, management and prognosis, and discuss the mechanisms which may be responsible.

Successful extracapsular cataract surgery depends on adequate mydriasis, which will facilitate the anterior capsulotomy and provide a full field of view throughout the operation. The surgeon, especially the neophyte, must recognise which irises may present a difficulty in establishing, maintaining, and reversing mydriasis, with or without the introduction of an intraocular lens. The author describes the preliminary assessment of the iris for disease, previous iris surgery, ease of dilatation, and the place of primary iridectomy. Topical and subconjunctival preoperative mydriatics are assessed, and a practical account of the pharmacological, mechanical, and surgical means of maintaining intra-operative mydriasis is given. The indication for iridectomy in extracapsular lens extraction with or without an intraocular lens is reviewed, and the postoperative manipulation of the iris is described with reference to the problems caused by rebound mydriasis.

The discriminate use of topically applied corticosteroids to modify or abolish the inflammatory response in herpetic stromal keratitis, has, as its objectives, the prevention of visual loss from corneal scarring and disorganization and a lessening of the morbidity associated with this disese. Steroids may be expected to have a profound anti-inflammatory effect in antibody-complement mediated inflammation and are effective in delayed hypersensitivity as in homograft rejection. The equally profound effect of pharmacological vasoconstriction may enable steroids to impede both afferent and efferent pathways in an immunological reflex arc, and they may be expected to reduce inflammation of nonimmunogenic origin. The adverse effects of the misapplication of these potent drugs in herpetic keratitis, in terms of an increase in the rate of complications and in the severity and morbidity of the disease, should be emphasized again.

The problem of finding an Evolutionary Stable Strategy (ESS) for an animal species is defined. It is shown how such strategies are a subset of the equilibrium solutions for a particular non-zero sum game. These equilibrium solutions are then shown to arise from the vertices of a particular convex polyhedron. A method of finding these equilibrium solutions through the vertices and then the ESS solutions is given. This is illustrated by a number of numerical examples taken from the literature. Finally an alternative approach based on solving a Linear Complementarity Problem is discussed.

We define in this paper a rational approach to the management of the various stages of herpetic eye disease. We consider in more detail comparisons between idoxuridine (IDU), trifluorothymidine (F3T), and adenine arabinoside (Ara-a) (derived largely from clinical trials in herpetic ulcers). We discuss metaherpetic ulcers and certain aspects of keratoplasty.

Automated tritium-hydrogen exchange measurements have been made on the linear octapeptide Val(5)-angiotensin II amide. All six amide hydrogens of the peptide backbone are observable, and are resolved into three classes according to their exchange rates. The rate of exchange of the slowest class, t(1/2) of 300 min at 0 degrees C (pH 2.5), is compared with that of hydrogens that exchange abnormally slowly in other peptides. It is concluded that these slow hydrogens in angiotensin II are involved in secondary structure with either one or both forming stable, intramolecular hydrogen bonds. This finding demonstrates that linear peptides may have hydrogen-bonded conformations in aqueous solutions. Analysis of the pH dependence of the rate of exchange indicates that one peptide amide hydrogen, namely that of the Asn(1)-Arg(2) peptide bond, is not involved in hydrogen bonding and is freely accessible to the solvent. Thus, the finding of internal hydrogen bonding, together with the assignment of the environment of one peptide bond, places major constraints on the number of allowable conformations of this linear polypeptide hormone.