Search

A conflict between Taiwan and China might involve a full-scale invasion, or a more limited coercion campaign in which China seeks to cause Taiwan enough pain to cause it to change its behavior. If the United States chooses to intervene in such a conflict on Taiwan's behalf, it can likely prevent China from invading Taiwan but might not be able to prevent Taiwan from being coerced. For this reason, the United States would be mistaken if it completely abandoned its policy of ambiguity about defending Taiwan. If the United States were to change its policy of ambiguity, it should do so only in the case of an invasion and remain ambiguous as to whether and how it would respond to a Chinese coercion campaign. [ABSTRACT FROM AUTHOR]

In Victory In War: Foundations of Modern Military Policy, William Martel attempts to provide a theory (actually, a 'pre-theory') of victory in war with the stated purpose of helping both [...]

Presents a reprint of the article `Avoiding Nuclear Anarchy: Continuing the Threat of Loose Russian Nuclear Weapons and Fissile Material,' on the nuclear challenges posed by the collapse of the former Soviet Union for American policy makers. Tactical nuclear weapons; Strategic nuclear weapons; Nuclear leakage; Recommendations.

Presents a study which aimed to examine the specific limitations and errors associated with garbage analysis in comparison to self-report measures. Sources of error in unobtrusive measures; Methodology; Correlation between self-report and garbage measures when examining sensitive products; Advantages and limitations of garbage analysis.

Background: An obesity paradox, whereby patients with higher body mass index (BMI) experience improved outcomes, has been described for ischemic stroke. It is unclear whether this applies to patients undergoing mechanical thrombectomy (MT) for large vessel occlusion (LVO)., Methods: Mechanical thrombectomies for anterior circulation LVO between 2015 and 2021 at a single institution were reviewed. Multivariable logistic regressions were used to determine the association between BMI and favorable functional outcome (90-day modified Rankin Scale 0-2), intracranial hemorrhage, and malignant middle cerebral infarction. A systematic review was performed to identify studies reporting the effect of BMI on outcomes among patients receiving MT for LVO. The data from the systematic review were combined with the institutional data by using a random effects model., Results: The institutional cohort comprised 390 patients with a median BMI of 27 kg/m 2 . Most patients were obese [36.7% (BMI ≥ 30 kg/m 2 )], followed by overweight [30.5% (BMI ≥ 25 and < 30 kg/m 2 )], normal [27.9% (BMI ≥ 18.5 and < 25 kg/m 2 )], and underweight [4.9% (BMI < 18.5 kg/m 2 )]. As a continuous variable, BMI was not associated with any of the outcomes. When analyzing BMI ordinally, obesity was associated with lower odds of favorable 90-day modified Rankin Scale (odds ratio 0.42, 95% confidence interval 0.20-0.86). The systematic review identified three eligible studies comprising 1,348 patients for a total of 1,738 patients. In the random effects model, there was no association between obesity and favorable outcome (odds ratio 0.89, 95% confidence interval 0.63-1.24)., Conclusions: Obesity is not associated with favorable outcomes in patients undergoing MT for LVO., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: Mechanical thrombectomy (MT) improves outcomes in patients with LVO but many still experience mortality or severe disability. We sought to develop machine learning (ML) models that predict 90-day outcomes after MT for LVO., Methods: Consecutive patients who underwent MT for LVO between 2015-2021 at a Comprehensive Stroke Center were reviewed. Outcomes included 90-day favorable functional status (mRS 0-2), severe disability (mRS 4-6), and mortality. ML models were trained for each outcome using prethrombectomy data (pre) and with thrombectomy data (post)., Results: Three hundred and fifty seven patients met the inclusion criteria. After model screening and hyperparameter tuning the top performing ML model for each outcome and timepoint was random forest (RF). Using only prethrombectomy features, the AUCs for the RF pre models were 0.73 (95% CI 0.62-0.85) for favorable functional status, 0.77 (95% CI 0.65-0.86) for severe disability, and 0.78 (95% CI 0.64-0.88) for mortality. All of these were better than a standard statistical model except for favorable functional status. Each RF model outperformed Pre, SPAN-100, THRIVE, and HIAT scores (P < 0.0001 for all). The most predictive features were premorbid mRS, age, and NIHSS. Incorporating MT data, the AUCs for the RF post models were 0.80 (95% CI 0.67-0.90) for favorable functional status, 0.82 (95% CI 0.69-0.91) for severe disability, and 0.71 (95% CI 0.55-0.84) for mortality., Conclusions: RF models accurately predicted 90-day outcomes after MT and performed better than standard statistical and clinical prediction models., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: We evaluated how systolic blood pressure (SBP) and mean arterial pressure (MAP) parameters between presentation and reperfusion influence functional status and intracranial hemorrhage (ICH)., Methods: All patients who underwent MT for LVO at a single institution were reviewed. Independent variables included SBP and MAP measurements obtained on presentation, between presentation and reperfusion (pre-reperfusion), and between groin puncture and reperfusion (thrombectomy). Mean, minimum, maximum, and standard deviations (SD) for SBP and MAP were calculated. Outcomes included 90-day favorable functional status, radiographic ICH (rICH), and symptomatic ICH (sICH)., Results: 305 patients were included. Higher pre-reperfusion SBP max was associated with rICH (OR 1.41, 95% CI 1.08-1.85) and sICH (OR 1.84, 95% CI 1.26-2.72). Higher SBP SD was also associated with rICH (OR 1.38, 95% CI 1.06-1.81) and sICH (OR 1.59, 95% CI 1.12-2.26). Greater SBP max (OR 0.64, 95% CI 0.47-0.86), MAP max (OR 0.72, 95% CI 0.52-0.97), SBP SD (OR 0.63, 95% CI 0.46-0.86), and MAP SD (0.63, 95% CI 0.45-0.84) during thrombectomy were associated with lower odds of 90-day favorable functional status. In a subgroup analysis, these associations were primarily limited to patients with intact collateral circulation. Optimal SBP max cutoffs for predicting rICH were 171 (pre-reperfusion) and 179 mmHg (thrombectomy). Cutoffs for predicting sICH were 178 (pre-reperfusion) and 174 mmHg (thrombectomy)., Conclusion: Greater maximum BP and variability in BP during the pre-reperfusion period are associated with unfavorable functional status and ICH after MT for anterior circulation LVO., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: Prediction of malignant middle cerebral artery infarction (MMI) could identify patients for early intervention. We trained and internally validated a ML model that predicts MMI following mechanical thrombectomy (MT) for ACLVO., Methods: All patients who underwent MT for ACLVO between 2015 - 2021 at a single institution were reviewed. Data was divided into 80% training and 20% test sets. 10 models were evaluated on the training set. The top 3 models underwent hyperparameter tuning using grid search with nested 5-fold CV to optimize the area under the receiver operating curve (AUROC). Tuned models were evaluated on the test set and compared to logistic regression., Results: A total of 381 patients met the inclusion criteria. There were 50 (13.1%) patients who developed MMI. Out of the 10 ML models screened on the training set, the top 3 performing were neural network (median AUROC 0.78, IQR 0.72 - 0.83), support vector machine ([SVM] median AUROC 0.77, IQR 0.72 - 0.83), and random forest (median AUROC 0.75, IQR 0.68 - 0.81). On the test set, random forest (median AUROC 0.78, IQR 0.73 - 0.83) and neural network (median AUROC 0.78, IQR 0.73 - 0.83) were the top performing models, followed by SVM (median AUROC 0.77, IQR 0.70 - 0.83). These scores were significantly better than those for logistic regression (AUROC 0.72, IQR 0.66 - 0.78), individual risk factors, and the Malignant Brain Edema score (p < 0.001 for all)., Conclusion: ML models predicted MMI with good discriminative ability. They outperformed standard statistical techniques and individual risk factors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Radial access is an increasingly popular approach for performing cerebral angiography. There are two sites for radial artery puncture: proximal transradial access (pTRA) in the wrist and distal transradial access (dTRA) in the snuffbox. These approaches have not been directly compared., Materials and Methods: Consecutive diagnostic cerebral angiograms performed at a single institution were retrospectively reviewed. Outcomes included fluoroscopy time, radiation dose, contrast volume, time to obtain access, procedure duration, and time to discharge home. Success rates as well as minor and major complication rates associated with each approach were also compared. Multivariate linear regression models were used to determine the relationship between access site and outcomes while adjusting for covariates., Results: A total of 287 angiograms on 244 patients met the inclusion criteria. pTRA was associated with shorter fluoroscopy time (ß -2.54, 95% CI -4.18 - -0.9, p = 0.003) and lower radiation dose (ß -242.89, 95% CI -351.55 - -134.24, p < 0.001), but not contrast volume. Time to obtain access, procedure duration, and time to discharge home were similar between approaches. A total of 10 minor complications occurred with similar rates for each approach (8 for dTRA, 2 for pTRA, p = 0.168) and there were no major complications. The conversion rate to femoral access was low (1.05% overall) and did not differ with approach., Conclusion: dTRA and pTRA are associated with similarly high rates of safety and efficacy. Procedure duration, time to obtain access, and time to discharge did not differ between approaches., Competing Interests: Declarations of Competing Interest None, (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Distal transradial access (dTRA) has several advantages compared with proximal transradial access (pTRA) for cerebral angiography. The learning curve for transitioning from pTRA to dTRA has not been described., Methods: Retrospective analysis of the first 75 diagnostic cerebral angiograms performed with dTRA by a single operator was performed. Outcomes included time for sheath insertion, sheath to first vessel time, procedure duration, fluoroscopy time, radiation dose, and contrast volume. Their associations with procedure number were evaluated with multivariate linear regressions, segmented linear regression, and locally weighted regression (LOESS)., Results: The mean age of patients was 56.1 years and 61.3% were female. Seventy-four of 75 angiograms were successfully completed with dTRA. There were 3 minor and no major complications. After adjusting for covariates, sheath to first vessel time (β = -0.50, P < 0.001) and procedure duration (β = -0.26, P = 0.002) were associated with procedure number. Time for sheath insertion, fluoroscopy time, radiation dose, and contrast volume were not associated with procedure number. Segmented linear regression identified break-points of 33 for sheath to first vessel time and 11 for procedure duration, which corresponded to the procedure number after which these outcomes trended down. LOESS models for time to sheath placement, procedure duration, fluoroscopy time, and radiation dose predicted minimum values between procedures 40-50., Conclusions: Transitioning from pTRA to dTRA for diagnostic cerebral angiography is feasible and safe. The learning curve is overcome between procedures 11 and 33, and further refinement in performance occurs through procedures 40-50., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The flashing lights and celebratory sounds that dominate slot-machine gambling are believed to promote engagement and motivation to keep playing. However, these cues are often presented in the absence of reward, and previous research suggests that this reward uncertainty, which degrades their predictive value, also increases their incentive value. Here, we used autoshaping to tease apart the impact of reward uncertainty on the predictive and incentive value of a conditioned stimulus (CS) using serial cues. Each CS trial began with the presentation of a predictive CS1, followed by a CS2, holding primarily incentive value, because of its proximity to sucrose reward delivery, under Certain (100%-1) or Uncertain (50%-1- 2-3) reward conditions. Subsequently, we tested the impact of amphetamine and nicotine on cue attraction, and the ability of these cues to either serve as a conditioned reinforcer, or promote motivation for sucrose during a progressive ratio task. Finally, we measured anxiety behavior, and examined its interaction with each cue and uncertainty. Our results suggest that reward uncertainty increases attraction to the incentive CS2 and its ability to trigger motivation and reward-seeking. However, although the CS2 is largely ignored under Certain conditions, both CS1 and CS2 become conditioned reinforcers for both groups. Finally, amphetamine reduced the attraction of the CS1 for both groups but had no effect on the attraction of the CS2. These results suggest that reward uncertainty recruits and increases the incentive value of cues with limited predictive value and highlights the distinction between cue attraction, reward-seeking and conditioned reinforcer properties., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hybridomas secreting anti-HBs were produced by fusion of either adw or ayw HBsAg primed mouse spleen cells with either P3 X63 Ag8 or P3 NSI 1 Ag4 1 mouse myeloma cell lines. Individual anti-HBs secreting clones were isolated by limiting dilution procedures, and six cell lines have been established, namely, BX182, BX259, BX248, CN324, DN283, and DN296. Progenies of each cell line were derived from a single clone obtained from three subclonings of six anti-HBs positive initial fusion colonies. Clones were passaged in tissue culture and as tumors in syngeneic mice for upwards of six months. Anti-HBs of each line showed characteristic reactivity (detection) patterns in radioimmunoassay using different antigen subtype solid phases followed by either 125I-HBsAg or 125I-goat anti-mouse IgG probe. The specificity of the anti-HBs from each clone for the subdeterminants of HBsAg was identified by their reaction with 125I-HBsAg ligands of several subtypes in a radioimmunoprecipitation assay. Four types of reaction were identified and correlated to the conventional serological subtyping definitions; they were anti-HBs/a (BX259 and CN324), anti-HBs/d (BX182), and possibly anti-HBs/w (BX248 and DN296) and anti-HBs/y (DN283). These monoclonal antibodies will be important for the elucidation of the antigenic structure of native HBsAg and will provide valuable reagents for both antigen detection and subtyping.

The synthesis of the two respiratory syncytial (RS) virus glycoproteins (VP66 and VP84) was examined under standard conditions and after treatment with tunicamycin and monensin. The protein backbone for VP66, the fusion protein (F1,2) is cotranslationally glycosylated to form F0, which is cleaved to form F1,2 by 20 min of chase. Monensin treatment inhibited the cleavage of F0 over an 80 min chase period, indicating that this occurred late in the transit of F0 through the Golgi apparatus or after exit from the Golgi apparatus. Tunicamycin treatment resulted in the synthesis of a 50K to 55K unglycosylated F0 which is cleaved to a 40K protein. VP84, the large glycoprotein, contains a protein backbone of only 26K to 30K which is modified by N-linked and probable O-linked glycosylation. Tunicamycin treatment results in the synthesis of a 70K protein (p70) which incorporates [3H]glucosamine and [3H]fucose but not [3H]mannose. Glycosylated precursors varying in mol. wt. from 29K to 45K (p45) are found in infected cells at regular 2K to 3K intervals, producing a 'ladder' effect. The step from p45 to VP84 is severely delayed by monensin treatment thereby enhancing the 'ladder' effect of the precursors.

Five nonoverlapping antigenic sites (sites I through V) of woodchuck hepatitis virus surface antigen were identified with competitive binding assays involving monoclonal antibodies. Site I contributed to cross-reactions among surface antigens of hepatitis B-like viruses infecting woodchucks, ground squirrels, and humans. At least three distinct sites (sites I, II, and III) are responsible for cross-reactions between woodchuck and ground squirrel hepatitis virus surface antigens. Sites IV and V of woodchuck hepatitis virus surface antigen are not major cross-reactive sites, suggesting that these elicit virus-specific antibodies. There were no cross-reactions with duck hepatitis B virus surface antigen.

Monoclonal antibodies to human respiratory syncytial (RS) virus-specific antigens can be obtained without preliminary recourse to large-scale culture and purification of the virion. Lytically infected human and persistently infected murine cultured cells expressing RS virus-specific cell surface and cytoplasmic antigens were substituted as priming immunogens and as substrates in solid-phase antibody radioimmunoassays. Seven hybridoma clones secreting murine IgG of either the gamma 1 or the gamma 2a subclass bearing kappa light chains were isolated. Two of the antibodies were specific for cell surface viral antigens, but only one was able to neutralize RS virus infectivity. The five remaining antibodies did not neutralize virus infectivity and were specific for viral antigens associated with large cytoplasmic inclusions as judged by indirect immunofluorescence (IF) analysis on fixed infected cells. Similar IF analysis using live cells revealed that those antigens, associated with the cytoplasmic inclusions in both the human and murine infected cells, were not expressed on the cell surface of the live infected human cells, but were expressed on the cell surface of the live infected murine cells. Monoclonal antibodies generated via the present system will prove useful in the immunological analysis of viral components which are specific pathogenic functions, such as infectivity, and those which may be abnormally exposed at the surface of persistently infected cells.

The effects of spironolactone and cirrhosis on the measurement of serum digoxin levels by radioimmunoassay were studied in patients not receiving cardiac glycosides. Three groups of 10 patients each were studied. Groups 1 and 2 included patients with alcoholic cirrhosis, with Group 1 patients receiving spironolactone and Group 2 receiving no spironolactone. Group 3, the control group, included patients who were not receiving spironolactone and did not have cirrhosis. Apparent digoxin serum levels were measured by radioimmunoassay, and the mean levels of each group were compared. Group 1 had significantly higher apparent digoxin levels (1.3 +/- 0.62 ng/ml, p 0.05) than Groups 2 or 3. The apparent digoxin level of Group 2 (0.74 +/- 0.44 ng/ml) did not differ significantly from that of Group 3 (0.40 +/- 0.35 ng/ml). Significant correlations were found between apparent serum digoxin levels and daily spironolactone dose (Group 1), SGOT levels (Group 1), and prothrombin time/control ratios (Group 2 and all groups combined). Spironolactone appears to increase digoxin levels measured by radioimmunoassay. The effect of cirrhosis on digoxin radioimmunoassay has not been confirmed.

The hepatitis B-like viruses (human hepatitis B virus, woodchuck hepatitis virus, ground squirrel hepatitis virus, and duck hepatitis B virus) are hepatotropic DNA viruses which have been referred to collectively as "hepadnaviruses." Using a murine monoclonal antibody (101-2) to the surface antigen of woodchuck hepatitis virus, we have shown that the surface antigens of mammalian hepadnaviruses (HBsAg, WHsAg, and GSHsAg) are antigenically related via a common determinant (HV/101). Furthermore, analysis with other monoclonal antibodies to WHsAg revealed that WHsAg and GHsAg are antigenically distinct, although the antigens had more determinants in common with each other than with HBsAg. The hepadnavirus group-specific antibody (101-2) reacted with HBsAg subtypic variants in a group-specific rather than subtype-specific manner. In conjunction with observations with an HBsAg-specific, group-reactive monoclonal antibody (BX259), the present data suggest that there are at least two group-reactive epitopes of HBsAg: one which is virus specific (HBV/259) and one which is common to two other mammalian hepadnaviruses (HV/101).