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Objective Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer’s disease (AD). We also aimed to determine the cutoffs for amyloid positivity for quantitative measures by investigating the agreement between quantitative and visual assessments. Methods Ninety-nine patients suspected of having AD underwent 18F-florbetapir PET at five institutions. Site-specialized physicians provided a diagnosis of AD or non-AD with a percentage estimate of their confidence and their plan for patient management in terms of medication, prescription dosage, additional diagnostic tests, and care planning both before and after receiving the amyloid imaging results. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by four board-certified nuclear medicine physicians. The PET images were also quantitatively analyzed using the standardized uptake value ratio (SUVR) and Centiloid (CL) scale. Results Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ2 = 5.334, p = 0.0209). Amyloid PET results also resulted in at least one change to the patient management plan in 42 patients (42%), mainly medication (20 patients, 20%) and care planning (25 patients, 25%). Receiver-operating characteristic analysis determined the best agreement of the quantitative assessments and visual interpretation of PET scans to have an area under the curve of 0.993 at an SUVR of 1.19 and CL of 25.9. Conclusion Amyloid PET using 18F-florbetapir PET had a substantial clinical impact on AD and non-AD diagnosis and on patient management by enhancing diagnostic confidence. In addition, the quantitative measures may improve the visual interpretation of amyloid positivity.

Background Although a large amount of evidence has revealed that amyloid β (Aβ), especially Aβ oligomers, protofibrils, and pyroglutamated Aβs, participate primarily in the pathophysiological processes of Alzheimer’s disease, most clinical trials of anti-Aβ antibody therapy have never acquired successful efficacy in human clinical trials, partly because peripheral administration of antibody medications was unable to deliver sufficient amounts of the molecules to the brain. Recently, we developed polymeric nanomicelles capable of passing through the blood–brain barrier that function as chaperones to deliver larger amounts of heavy molecules to the brain. Herein, we aimed to evaluate the efficacy of newly developed antibody 6H4 fragments specific to Aβ oligomers encapsulated in polymeric nanomicelles on the development of Alzheimer’s disease pathology in Alzheimer’s disease model mice at the age of emergence of early Alzheimer’s disease pathology. Results During the 10-week administration of 6H4 antibody fragments in polymeric nanomicelles, a significant reduction in the amounts of various toxic Aβ species, such as Aβ oligomers, toxic Aβ conformers, and pyroglutamated Aβs in the brain was observed. In addition, immunohistochemistry indicated inhibition of diameters of Aβ plaques, Aβ-antibody immunoreactive areas, and also plaque core formation. Behavioral analysis of the mice model revealed that the 6H4 fragments-polymeric nanomicelle group was significantly better at maintaining long-term spatial reference memory in the probe and platform tests of the water maze, thereby indicating inhibition of the pathophysiological process of Alzheimer’s disease. Conclusions The results indicated that the strategy of reducing toxic Aβ species in early dementia owing to Alzheimer’s disease by providing sufficient antibodies in the brain may modify Alzheimer’s disease progression.

In the present study, we analyzed the inflammatory profiles of brain tissues obtained from patients with progressive multifocal leukoencephalopathy (PML) due to John Cunningham (JC) virus infection to identify potential prognostic factors. The study included seven patients (two men, five women) who had been pathologically diagnosed with PML, and all of whom were HIV negative. Fixed brain samples were analyzed via hematoxylin and eosin (HE) staining and Kluver–Barrera (KB) staining. We then performed immunohistochemistry (IHC) specific to JC virus capsid proteins (VP1 and VP2/3) and lymphocyte surface markers (CD4, CD8, CD138, and PD-1). The mean age at onset was 53.4, while the mean duration until biopsy/autopsy was 4.7 months. Four patients were included in the good prognosis (GP) group, while three were included in the poor prognosis (PP) group. Pathological analysis revealed a significantly larger number of CD4-positive T-cell infiltrations (P = .029) in the GP group, along with a preserved CD4:CD8 ratio. Larger numbers of CD138-positive plasma cells were also observed in the GP group (P = .029) than in the PP group. Linear regression analyses revealed a significant association between the numbers of CD138-positive plasma cells and PD-1-positive cells (R2 = 0.80). Viral loads in the cerebrospinal fluid, a controlled inflammatory response mediated by CD4- and CD8-positive T cells, and plasma cells are associated with PML prognosis. Our findings further indicate that regulatory plasma cells may regulate inflammatory T-cell activity via a PD-1/PD-L1 immuno-checkpoint pathway, thereby protecting the uninfected brain from excessive immune-mediated damage during an active JC virus infection.

No evidence of disease activity-3 (NEDA-3), defined as absence of clinical relapse, disability progression, and brain magnetic resonance imaging (MRI) activity, has emerged as the therapeutic target of disease-modifying therapy for multiple sclerosis (MS). However, recent studies have revealed that NEDA-3 might not be sufficient to prevent cognitive deterioration and predict long-term disability. In addition to NEDA-3, brain atrophy has recently been recognized as a pivotal biomarker that is closely associated to disability in patients with MS. This retrospective observational study included 22 Japanese MS patients with relatively mild disease (median expanded disability status scale = 1.75). Fifteen patients (68%) received disease-modifying therapy (DMT), including interferon (IFN)-β (n = 6), IFN-β, or azathioprine followed by fingolimod (n = 4), fingolimod (n = 4), and IFN-β followed by natalizumab (n = 1). It revealed that 14 (64.6%) patients achieved NEDA-3 in the 2-year observational period. However, nine (64.3%) of the patients with NEDA-3 were revealed to have a significant BVL, defined as ≥ 0.4% per year. Importantly, these nine patients included all patients receiving IFN-β therapy (n = 6), whereas patients without BVL included none of these patients. Conversely, patients treated with fingolimod following IFN-β did not have significant BVL. These results indicate that evaluation of NEDA-4 is encouraged especially in patients with IFN-β therapy in MS clinical practice in Japan although Japanese MS patients have generally been thought to possess a milder disease including brain atrophy compared to their Western counterparts.

Three-dimensional aggregation and organ culture methods are critical for recreating in vivo cellular phenomena outside the body. Previously, we used the conventional gas liquid interphase organ culture method to induce complete mouse spermatogenesis. After incorporating microfluidic systems, we achieved a significant increase in efficiency and duration of spermatogenesis. One of the major drawbacks preventing the popularization of microfluidics, however, is the use of a power-pump to generate medium flow. In this study, we produced a pumpless microfluidic device using hydrostatic pressure and a resistance circuit to facilitate slow, longer lasting medium flow. During three months of culture, results in induction and maintenance of spermatogenesis showed no difference between pumpless and pump-driven devices. Correspondingly, the spermatogonial population was favorably maintained in the pumpless device compared to the conventional method. These results show the advantage of using microfluidic systems for organ culture experiments. Our pumpless device could be applied to a variety of other tissues and organs, and may revolutionize organ culture methods as a whole.

Although there is strong evidence for shared abstract grammatical structure in bilingual speakers from studies of sentence production, comparable evidence from studies of comprehension is lacking. Twenty-seven (N = 27) English-German bilingual adults participated in a structural priming study where unambiguous English subject and object relative clause (RC) structures were used to prime corresponding subject and object RC interpretations of structurally ambiguous German RCs. The results showed that English object RCs primed significantly greater object RC interpretations in German in comparison to baseline and subject RC prime conditions, but that English subject RC primes did not change the participants' baseline preferences. This is the first study to report abstract crosslinguistic priming in comprehension. The results specifically suggest that word order overlap supports the integration of syntactic structures from different languages in bilingual speakers, and that these shared representations are used in comprehension as well as production.

In contrast to cell cultures, particularly to cell lines, tissues or organs removed from the body cannot be maintained for long in any culture conditions. Although it is apparent that in vivo regional homeostasis is facilitated by the microvascular system, mimicking such a system ex vivo is difficult and has not been proved effective. Using the culture system of mouse spermatogenesis, we addressed this issue and devised a simple microfluidic device in which a porous membrane separates a tissue from the flowing medium, conceptually imitating the in vivo relationship between the microvascular flow and surrounding tissue. Testis tissues cultured in this device successfully maintained spermatogenesis for 6 months. The produced sperm were functional to generate healthy offspring with micro-insemination. In addition, the tissue kept producing testosterone and responded to stimulation by luteinizing hormone. These data suggest that the microfluidic device successfully created in vivo-like conditions, in which testis tissue maintained its physiologic functions and homeostasis. The present model of the device, therefore, would provide a valuable foundation of future improvement of culture conditions for various tissues and organs, and revolutionize the organ culture method as a whole.

A 52-year-old man suffering from monocular blindness, with light perception only, was admitted to our hospital. The symptom had begun as low vision and developed rapidly within 3 weeks into monocular blindness in the right eye, with no other systemic manifestations. Imaging examinations revealed multiple hepatocellular carcinomas in the cirrhotic liver, and tumors at the skull base and vertebra. A pathological and immunochemical study of specimens obtained by endoscopic transnasal tumor biopsy and laminectomy revealed them to be metastatic hepatocellular carcinomas (HCCs). Although the patient underwent radiation therapy and chemotherapy, he died 5 months after admission to our hospital. The cranial HCC, involving only the optic canal, may have disturbed the optic nerve in preference to the other cranial nerves. This is the first report of a HCC patient with monocular blindness as the initial presentation of the disease.

We develop a two-country model of mixed oligopoly with Hotelling-type spatial competition to examine how market integration influences the location of firms. The results show that the initial location of a public firm is associated with the location choices of the firm after market integration.

We analyze a duopolistic health care market in which a rural public hospital competes against an urban public hospital on medical quality, by using a Hotelling-type spatial competition model extended into a two-region model. We show that the rural public hospital provides excess quality for each unit of medical service as compared to the first-best quality, and the profits of the rural public hospital are lower than those of the urban public hospital because the provision of excess quality requires larger expenditure. In addition, we investigate the impact of the partial (or full) privatization of local public hospitals.

We study smooth functions in several variables with a Lipschitz derivative. It is shown that these functions have the "envelope property": Around zero-derivative points, and only around such points, the functions are envelopes of a quadratic parabolloid. The property is used to reformulate Fermat's extreme value theorem and the Theorem of Lagrange under slightly more restrictive assumptions but withouth the derivatives.

We investigate a health care market with uncertainty in a mixed duopoly, where a partially privatized public hospital competes against a private hospital in terms of quality choice. We use a simple Hotelling-type spatial competition model by incorporating mean-variance analysis and the framework of partial privatization. We show how the variance in the quality perceived by patients affects the true quality of medical care provided by hospitals. In addition, we show that a case exists in which the quality of the partially privatized hospital becomes higher than that of the private hospital when the patient's preference for quality is relatively high.

In Japan, most cancer patients die in the hospital. The aim of this study was to assess the quality of end-of-life treatment for dying cancer patients in general wards and palliative care unit (PCU). A retrospective chart review study was conducted. The following data on cancer patients who died in general wards (N = 104) and PCU (N = 201) at a regional cancer center were collected: do-not-resuscitate (DNR) decisions, treatments in the last 48 h of life, and aggressiveness of cancer care for dying patients. DNR orders were documented for most patients (94% in general wards, 98% in PCU, p = 0.067) and families usually consented (97%, 97%, p = 0.307). Comparison of general wards with PCU showed that, in the last 48 h of life, significantly more patients in general wards received life-sustaining treatment (resuscitation, 3.8%, 0%, p = 0.001; mechanical ventilation, 4.8%, 0%, p = 0.004), large volume hydration (>1,000 ml/day, 67%, 10%, p

Objective To determine the timing of development of suicidal ideation and factors associated therewith in suicide attempters who required psychiatric emergency treatment. Methods Of a total of 2818 suicide attempters in Japan who presented to the primary or secondary emergency department of Iwate Medical University Hospital (hereinafter, referred to as our hospital) or Iwate Prefecture Advanced Emergency and Critical Care Center (hereinafter, referred to as the emergency center), an affiliated institution to our hospital, during the 12-year period from April 1, 2002–March 31, 2014, 2274 patients for whom the timing of development of suicidal ideation was identified were included in the study. The study subjects were classified into three groups according to the timing of development of suicide ideation: the “same-day” group, those who developed suicidal ideation and attempted suicide on the same day; the “short-term” group, those who developed suicidal ideation 2–7 days before attempting suicide; and the “long-term” group, those who developed suicidal ideation more than 7 days before attempting suicide. Factors associated with the development of suicidal ideation in each group were analyzed by a multiple logistic regression analysis with background factors, the diagnosis according to the ICD and the situations before and after the suicide attempt as explanatory variables. Results The same-day group was characterized by a high female ratio, high global functioning, low stress level, non-depressed status and a lack of seeking consultation. In contrast, the long-term group was characterized by low global functioning and a high stress level, suggesting that these patients exhibit consultation behavior, but have not received psychiatric services. In the short-term group, only male gender was identified as a significant factor. Discussion For those patients who developed suicidal ideation and attempted suicide on the same day, treatment strategies focusing on the acquisition of coping skills and stress management are recommended. For those with suicidal ideation lasting for more than a week or recurrent ideation, early detection and subsequent early treatment of such ideation are essential. In intermediate cases, treatment strategies that make the full use of mental health management in the workplace and gate-keeping are likely to be effective.

The topological aspects of electrons in solids emerge in realistic matters as represented by topological insulators. They are expected to show a variety of new magneto-electric phenomena, and especially the ones hosting superconductivity are strongly desired as the candidate for topological superconductors (TSC). Possible TSC materials have been mostly developed by introducing carriers into topological insulators, nevertheless, those exhibiting indisputable superconductivity free from inhomogeneity are very few. Here we report on the observation of topologically-protected surface states in a centrosymmetric layered superconductor, beta-PdBi2, by utilizing spin- and angle-resolved photoemission spectroscopy. Besides the bulk bands, several surface bands, some of which crossing the Fermi level, are clearly observed with symmetrically allowed in-plane spin-polarizations. These surface states are precisely evaluated to be topological, based on the Z2 invariant analysis in analogy to 3-dimensional strong topological insulators. beta-PdBi2 may offer a TSC realized without any carrier-doping or applying pressure, i.e. a solid stage to investigate the topological aspect in the superconducting condensate., Comment: 17 pages, 4 figures

The Ubc13 E2 ubiquitin-conjugating enzyme is key in the process of 'tagging' target proteins with lysine 63-linked polyubiquitin chains, which are essential for the transmission of immune receptor signals culminating in activation of the transcription factor NF-kappaB. Here we demonstrate that conditional ablation of Ubc13 resulted in defective B cell development and in impaired B cell and macrophage activation. In response to all tested stimuli except tumor necrosis factor, Ubc13-deficient cells showed almost normal NF-kappaB activation but considerably impaired activation of mitogen-activated protein kinase. Ubc13-induced activation of mitogen-activated protein kinase required, at least in part, ubiquitination of the adaptor protein IKKgamma. These results show that Ubc13 is key in the mammalian immune response.

The presenilin proteins (PS1 and PS2) and their interacting partners nicastrin, aph-1 (refs 4, 5) and pen-2 (ref. 5) form a series of high-molecular-mass, membrane-bound protein complexes that are necessary for gamma-secretase and epsilon-secretase cleavage of selected type 1 transmembrane proteins, including the amyloid precursor protein, Notch and cadherins. Modest cleavage activity can be generated by reconstituting these four proteins in yeast and Spodoptera frugiperda (sf9) cells. However, a critical but unanswered question about the biology of the presenilin complexes is how their activity is modulated in terms of substrate specificity and/or relative activities at the gamma and epsilon sites. A corollary to this question is whether additional proteins in the presenilin complexes might subsume these putative regulatory functions. The hypothesis that additional proteins might exist in the presenilin complexes is supported by the fact that enzymatically active complexes have a mass that is much greater than predicted for a 1:1:1:1 stoichiometric complex (at least 650 kDa observed, compared with about 220 kDa predicted). To address these questions we undertook a search for presenilin-interacting proteins that differentially affected gamma- and epsilon-site cleavage events. Here we report that TMP21, a member of the p24 cargo protein family, is a component of presenilin complexes and differentially regulates gamma-secretase cleavage without affecting epsilon-secretase activity.

Bone marrow cells (BMCs) have been shown to differentiate into a liver cell lineage, but little is known about their dynamics following transplantation. BMCs were cultured to investigate the expression of liver-specific genes in vitro and transplanted into in vivo liver-injury models to elucidate their dynamics in the liver. The mRNA expression of various liver-specific genes in BMCs cocultured with hepatocytes was analyzed using reverse transcription-polymerase chain reaction. BMCs from transgenic rats expressing green fiuorescent protein were transplanted into the spleen of rat liver-injury models induced with 2-acetylaminofiuorene (2-AAF) or carbon tetrachloride (CCl4). BMCs were also transplanted directly into livers treated with CCl4 to determine which route is better for transplantation. BMCs differentiated into a liver cell lineage in vitro and expressed mRNAs consistent with mature hepatocytes, including albumin. The transplanted BMCs were found in the liver in the CCl4-induced injury model, but not in the 2-AAF-induced model. The hepatocyte growth factor and fibroblast growth factor mRNA levels in the liver were significantly higher in the CCl4-induced model than in the 2-AAF-induced model. Migration of BMCs to the liver was more effective following injection into the liver, rather than into the spleen. Cultured BMCs differentiated into a liver cell lineage are a potential source for cell transplantation. Transplantation is successful in the severely injured liver with a high level of expression of mRNAs for growth factors. Injection of BMCs directly into the liver is the preferred route of administration.

It is well known that a twice continuously differentiable function can be convexified by a simple quadratic term. Here we show that the convexification is possible also for every Lipschitz continuously differentiable function. This implies that the Liu---Floudas convexification works for, loosely speaking, almost every smooth program occurring in practice.

The fact that two disjoint convex sets can be separated by a plane has a tremendous impact on optimization theory and its applications. We begin the paper by illustrating this fact in convex and partly convex programming. Then we look beyond convexity and study general nonlinear programs with twice continuously differentiable functions. Using a parametric extension of the Liu-Floudas transformation, we show that every such program can be identified as a relatively simple structurally stable convex model. This means that one can study general nonlinear programs with twice continuously differentiable functions using only linear programming, convex programming, and the inter-relationship between the two. In particular, it follows that globally optimal solutions of such general programs are the limit points of optimal solutions of convex programs.

Signal transduction through Toll-like receptors (TLRs) originates from their intracellular Toll/interleukin-1 receptor (TIR) domain, which binds to MyD88, a common adaptor protein containing a TIR domain. Although cytokine production is completely abolished in MyD88-deficient mice, some responses to lipopolysaccharide (LPS), including the induction of interferon-inducible genes and the maturation of dendritic cells, are still observed. Another adaptor, TIRAP (also known as Mal), has been cloned as a molecule that specifically associates with TLR4 and thus may be responsible for the MyD88-independent response. Here we report that LPS-induced splenocyte proliferation and cytokine production are abolished in mice lacking TIRAP. As in MyD88-deficient mice, LPS activation of the nuclear factor NF-kappaB and mitogen-activated protein kinases is induced with delayed kinetics in TIRAP-deficient mice. Expression of interferon-inducible genes and the maturation of dendritic cells is observed in these mice; they also show defective response to TLR2 ligands, but not to stimuli that activate TLR3, TLR7 or TLR9. In contrast to previous suggestions, our results show that TIRAP is not specific to TLR4 signalling and does not participate in the MyD88-independent pathway. Instead, TIRAP has a crucial role in the MyD88-dependent signalling pathway shared by TLR2 and TLR4.

Venous congestion of the brainstem is an extremely rare complication of carotid-cavernous fistula (CCF). Here, we report a case in which MR imaging revealed characteristic changes associated with a simultaneous increase in pressure in the ophthalmic vein and anterior pontomesencephalic vein. Our patient was a 76-year-old woman who had been diagnosed with spinocerebellar ataxia type 31, had exophthalmos, conjunctival congestion in her left eye, worsening dysarthria, and gait instability. Ten days later, she was admitted to our hospital. A neurologic examination conducted upon admission revealed mydriasis, loss of light reflex, impaired superolateral movement of the left eye, and worsening ataxia with gait difficulty and slurred speech. Laboratory examinations revealed only high levels of serum anti-cardiolipin IgG antibody and the presence of cerebrospinal fluid myelin basic protein, but no other suggestive data of an inflammatory event. T2-weighted MRI revealed a dilated left superior ophthalmic vein and hyperintensity of the pons, mainly on the left side (Fig. 1a), which was depicted as low signal area with a linear high signal lesion in diffusion-weighted images (Fig. 1c), and T1-weighted imaging revealed an isointense mass with ring-shaped contrast enhancement after injection of gadolinium (Fig. 1b). Cerebral angiography confirmed the presence of a very weak, direct, highflow CCF in the left external carotid artery (Fig. 1d, e). The MR venography and venous phase of the angiography did not show any occlusion of veins. Methionine positron emission tomography revealed no tracer uptake in the lesion, which excluded the possibility of a brain tumor. Her symptoms were rapidly getting well before we tried an endovascular treatment. At 4 months, the MRI images showed a high signal spot at the left cerebellar peduncle and slight high signal on the left side of the pons (Fig. 1a). Most cases of idiopathic and traumatic CCF have been reported to be caused by dural arteriovenous fistulas (DAVF) [1]. The providing angiography images showed a shunt from the external carotid artery to the cavernous sinus. According to the Barrow classification, we diagnosed this case as an indirect fistula [2]. The pathomechanisms of venous congestion of the brainstem in CCF remain unknown, but variations in the drainage pattern of the superior petrosal sinus (SPS) and engorged veins in the surrounding brainstem were speculated to be important factors in most of the cases. A large flow volume shunted via the CCF [3, 4], occlusion of the superior or inferior petrosal sinus [5, 6], thrombosis of the dural sinuses or veins of the posterior fossa [4], and variations in venous drainage [7] have been speculated to be primary triggers for venous congestion. The most likely pathomechanism in this patient is that the CCF initially drained via the ophthalmic vein and recruited the prepontine venous plexus for drainage following partial thrombosis of the cavernous sinus. For the cause of the partial thrombosis, we speculate the possible mediation of antiphospholipid-related antibodies because antiphospholipid antibodies are known to be associated with cerebral venous thrombi, and recent studies have suggested that venous congestion and retrograde flow may cause a dysfunctional venous circulation [8]. Y. Ito N. Sanjo (&) K. Ishikawa O. Tao T. Yokota H. Mizusawa Department of Neurology and Neurological Science, Graduate School of Medical and Dental Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan e-mail: n-sanjo.nuro@tmd.ac.jp

Arbitrary perturbations of arbitrary coefficients in linear programming models on the canonical form are studied. Perturbations that preserve stability (lower semi-continuity of the feasible set mapping) are characterized in terms of subsets of the index set of the decision variable. A necessary condition for stability is used to formulate a method for identification of unstable perturbations. Instability is illustrated in various situations including multi-level decision making, descriptions of locally and globally optimal parameters in linear parametric programming, and a marginal value formula for models with a convex objective and linear canonical constraints.

Objective. To develop an ergonomically designed computerized recordkeeping tool for anesthesiologists that allows the clinician to maintain visual contact with the patient while performing recordkeeping. Methods.To simplify the human interface software, we developed two general use software components. All purpose menu type 1 (APM1) was used for entering events using a tree structured menu. APM1 was designed to adapt to the limits of human memory, by using Miller's rule of 7 to guide the input process. APM1 can be considered to be a three-dimensional table list consisting of 7 vertical and 7 horizontal choices, which has further 5 tree-structured divergences. APM1 is also completely configurable by the user. All purpose menu 2 (APM2) was used to implement the system-initiated human interface where the system will prompt the user by voice for each entry. When users touch a key on APM1 and APM2, the system was designed to respond with a voice prompt. A touch-screen was also utilized and designed to fit the anesthesia machine. The screen is equipped with a small speaker for voice response and a microphone for voice recognition. The positions of the screen are adjustable supported by a long flexible limb (85 cm). Results. After improving the design, systems were assembled for 10 operating rooms. Of the multiple features of the VOCAAR user interface, the following were well accepted by users and employed daily: touch-screen input, and voice response. The noncompulsory use rate was 87% during the initial 2 weeks, increased to 94% after 2 weeks and 100% after two months. The mean sound emission by voice response (n = 10, mean ± SD) was 8.2 ± 2.3 dB at the main anesthetist site (35 cm from the speaker mounted on the touch-screen), 2.2 ± 1.3 dB at the staff site (1.5 m from the touch-screen), which was only audible for anesthesiologist but for surgeon. Discussion. An EARK system was designed to allow the user to maintain visual contact with the patient while performing recordkeeping tasks. The combination of a mobile touch screen and voice response/recognition facilitated the design goals of the system. Although the system has enjoyed universal clinical acceptance, the voice functions remain too limited to satisfy the needs of a completely handsfree user interface. Enhancements to voice recognition technology will offer the potential for improved functionality. Additional research is also needed to better define the relationship between vigilance and visual contact with the patient.

Objective. In order to predict the partial pressure of volatile anesthetics in brain tissue, we developed a pharmacokinetic simulation model suitable for real time application. The accuracy of this model was examined by comparing the predicted values against measured values for blood sampled from the internal jugular vein, which was used as a measure of the partial pressure in the brain. Methods. Our model consists of six compartments: alveoli, arterial blood, a group of vessel-rich organs (VRG), muscle, fat, and venous blood. A volatile anesthetic, sevoflurane partial pressure in each compartment were calculated using the parameters of volume, blood flow, and solubility for each tissue as reported in previous studies. Simulated sevoflurane partial pressures in VRG were considered to reflect those in the brain. We studied 11 patients undergoing elective abdominal surgery or mastectomy. Sevoflurane was maintained at a concentration of 3% (by vaporizer setting) for 25 min. Sampling points were at 0 min (before sevoflurane administration) and 1, 2, 4, 9, 16, and 25 min after the start of inhalation. We measured the sevoflurane partial pressure in inspiratory gas (PIS), in end-expiratory gas (PETS), in arterial blood (PaS), and in internal jugular vein blood (PjS). These values were compared against those for the simulated brain (PBSsim). Results. The sevoflurane partial pressures increased, in order from least rapid to most rapid, as follows: PjS, PBSsim, PaS, PETS, and PIS. The differences between PjS and PBSsim were significantly smaller than those between PjS and PETS at all sampling points. PBSsim did not differ significantly from PjS at any sampling points after 4 min of inhalation, while PETS differed significantly from PjS at all sampling points. Conclusion.We conclude that our model is clinically useful for predicting sevoflurane partial pressure in the brain, assuming that PjS reflects the sevoflurane partial pressure in the brain.

Tension pneumoperitoneum may force gas into a small injured vessel if the opening is kept patent by surrounding tissues. However, the amount of carbon dioxide (CO2) that penetrates through injured or noninjured peritoneum has not been systematically determined. In 25 patients undergoing elective laparoscopic ultrasonography and cholecystectomy, CO2 output (VCO2) and O2 uptake (VO2) were measured at baseline and during anesthesia, pneumoperitoneum, laparoscopic surgical procedure (Surgery), and after hemostasis of the surgical field (Postsurgery). Before anesthesia, VCO2/BSA and VO2/BSA were 97.7 +/- 11.3 and 116.0 +/- 10.0 ml x min(-1) x m(-2), respectively. During anesthesia, they fell to 72.3 +/- 6.0 and 89.8 +/- 7.6 ml x min(-1) x m(-2), respectively (p < 0.05). VCO2/BSA increased to 96.0 +/- 11.1 at pneumoperitoneum (p < 0.05) and increased further to 126.1 +/- 11.0 ml x min(-1) x m(-2) at Surgery. It fell to 111.7 +/- 10.9 ml x min(-1) x m(-2) Postsurgery. VO2/BSA remained unchanged during pneumoperitoneum. Minute volume increased from 2.24 +/- 0.20 in anesthesia to 2.89 +/- 0.25, 4.01 +/- 0.32, and 3.46 +/- 0.28 L x min(-1) x m(-2) during pneumoperitoneum, Surgery, and Postsurgery, respectively, to maintain PaCO2. We conclude that the amount of CO2 absorbed following pneumoperitoneum prior to surgery is lower than that during Surgery or Postsurgery. The amount of CO2 absorbed through the surgical field was 2.3 times higher than that through the nonsurgical field while that from the peritoneum after hemostasis of surgical field was 1.6 times higher.

The pathogenesis of portal hypertensive gastropathy has not yet been thoroughly elucidated. Changes in the gastric surface mucus layer in prehepatic portal hypertensive and cirrhotic rat models were studied by observing frozen sections fixed with formaldehyde vapor and stained with hematoxylin and eosin. We produced prehepatic portal hypertensive rats by partial ligation of the portal vein, and cirrhotic rats by prolonged administration of carbon tetrachloride (CCl4) and phenobarbital sodium. The thickness of the corporal and antral gastric surface mucus was significantly reduced in prehepatic portal hypertensive and cirrhotic rats compared with the values obtained in control rats for portal hypertension (subjected to sham operation) and control rats for cirrhosis (treated with phenobarbital but not CCl4). These results indicate that the hemodynamic changes associated with portal hypertension reduce the thickness of the gastric surface mucus layer and may be one of the causes of the gastropathy associated with portal hypertension.

Mathematical programs, that become convex programs after “freezing” some variables, are termed partly convex. For such programs we give saddle-point conditions that are both necessary and sufficient that a feasible point be globally optimal. The conditions require “cooperation” of the feasible point tested for optimality, an assumption implied by lower semicontinuity of the feasible set mapping. The characterizations are simplified if certain point-to-set mappings satisfy a “sandwich condition”.

This paper provides an answer to the following basic problem of convex multi-objective optimization: Find a saddle-point condition that is both necessary and sufficient that a given point be Pareto optimal. No regularity condition is assumed for the constraints or the objectives.

We introduce and characterize a class of differentiable convex functions for which the Karush—Kuhn—Tucker condition is necessary for optimality. If some constraints do not belong to this class, then the characterization of optimality generally assumes an asymptotic form. We also show that for the functions that belong to this class in multi-objective optimization, Pareto solutions coincide with strong Pareto solutions,. This extends a result, well known for the linear case.