Abstract Despite advances in preventive strategies, cytomegalovirus (CMV) infection remains a major complication in solid organ and hematopoietic cell transplant recipients. CMV infection may fail to respond to commercially available antiviral therapies, with or without demonstrating genotypic mutation(s) known to be associated with resistance to these therapies. This lack of response has been termed “resistant/refractory CMV” and is a key focus of clinical trials of some investigational antiviral agents. To provide consistent criteria for future clinical trials and outcomes research, the CMV Resistance Working Group of the CMV Drug Development Forum (consisting of scientists, clinicians, regulatory officials, and industry representatives from the United States, Canada, and Europe) has undertaken establishing standardized consensus definitions of “resistant” and “refractory” CMV. These definitions have emerged from the Working Group’s review of the available virologic and clinical literature and will be subject to reassessment and modification based on results of future studies.

Symptomatic cytomegalovirus (CMV) disease has been the standard endpoint for clinical trials in organ transplant recipients. Viral load may be a more relevant endpoint due to low frequency of disease. We performed a meta-analysis and systematic review of the literature. We found several lines of evidence to support the validity of viral load as an appropriate surrogate end-point, including the following: (1) viral loads in CMV disease are significantly greater than in asymptomatic viremia (odds ratio, 9.3 95% confidence interval, 4.6-19.3); (2) kinetics of viral replication are strongly associated with progression to disease; (3) pooled incidence of CMV viremia and disease is significantly lower during prophylaxis compared with the full patient follow-up period (viremia incidence: 3.2% vs 34.3%; P < .001) (disease incidence: 1.1% vs 13.0%; P < .001); (4) treatment of viremia prevented disease; and (5) viral load decline correlated with symptom resolution. Based on the analysis, we conclude that CMV load is an appropriate surrogate endpoint for CMV trials in organ transplant recipients.

It has been emphasized that the anterior cruciate ligament plays an important role in the proprioceptive feedback system. The anterior cruciate ligament-hamstring reflex has been revealed in animal experiments, but it has not been established in humans. The purpose of this study was to demonstrate direct evidence of the anterior cruciate ligament-hamstring reflex arc. Nine knees in nine healthy subjects were investigated. The anterior cruciate ligament was stimulated by the use of wire electrodes inserted using an arthroscopic technique. Electromyographic signals from the biceps femoris and the semitendinosus muscles were recorded with surface electrodes. The change in electromyographic activity was analyzed after electrical stimulation in the normal knee condition, and again after intraarticular sensation had been interrupted with a local anesthetic. After electrical stimulation, subjects demonstrated increased electromyographic activity of the hamstring muscles in the normal knee condition. This response indicates the existence of an anterior cruciate ligament-hamstring reflex arc. Conversely, there was no change in activity for the hamstring muscle in the anesthetized knee because the afferent impulse from the neural elements of the anterior cruciate ligament had been removed.

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Independent regulatory analyses confirmed that baseline HCV RASs can reduce the efficacy of certain DAA-based regimens in selected patient groups. However, highly effective treatment options are available for patients with or without baseline RASs. (Hepatology 2018;67:2430-2448).

Our previous work presented explicit formulas for the generalized zeta function and the generalized Ihara zeta function corresponding to the Grover walk and the positivesupport version of the Grover walk on the regular graph via the Konno-Sato theorem, respectively. This paper extends these walks to a class of walks including random walks, correlated random walks, quantum walks, and open quantum random walks on the torus by the Fourier analysis.

Ant crickets (Orthoptera, Myrmecophilidae) are typical ant guests that obtain nourishment from the ants in their nests. Some ant crickets are host-specific, whereas other species are host-generalists. We investigated the behavioral polarization between the specialist cricket Myrmecophilus albicinctus and generalist Myrmecophilus formosanus. In the field, M. albicinctus was found exclusively in nests of Anoplolepis gracilipes (185/185), whereas 62 M. formosanus were found in nests of 9 ant species from 3 subfamilies. Behavioral observations revealed that M. albicinctus could not survive in the absence of A. gracilipes and was killed when it was introduced into colonies of non-host ant species. In addition, M. albicinctus showed intimate behavior, such as trophallaxis, with its host. In contrast, M. formosanus swiftly avoided frequent attacks by host ants, independently took food, and survived well in the absence of ants. Overall, the specialist adapted its behavior and physiology to those of a specific ant host, whereas the generalist adopted versatile parasitic behaviors, such as quick movements. Our findings revealed interspecific polarization in the degree of host dependence and inquilinehost interaction, and they indicate that trade-offs occur between specialization to specific hosts and retention of generalization in order to exploit alternative hosts.