The baseline recurrence risk of patients with intermediate-risk cervical cancer.

Objective:This study aimed to investigate the prognosis of patients with intermediate-risk cervical cancer and to evaluate the necessity of adjuvant therapy.Methods:We conducted a retrospective chart review of patients with stage IB-II cervical cancer who underwent type III radical hysterectomy with pelvic lymphadenectomy between 2008 and 2017. In our institution, radical hysterectomy is performed as an open surgery and not as a minimally invasive surgery, and adjuvant therapy is not administered to patients with intermediate-risk cervical cancer. The intermediate-risk group included patients with 2 or more of the following factors: tumor size >4 cm, stromal invasion >1/2, and lymphovascular stromal invasion. Intermediaterisk patients with squamous cell carcinoma were included in the I-SCC group, whereas those with endocervical adenocarcinoma, usual type, or adenosquamous carcinoma were included in the I-Adeno group.Results:There were 34 and 18 patients in the I-SCC and I-Adeno groups, respectively. The 5-year recurrence-free survival (RFS) and overall survival rates in the I-SCC group were 90.5% (95% confidence interval [CI], 85.3-95.7%) and 100% (95% CI, 100%), respectively, whereas those in the I-Adeno group were 54.9% (95% CI, 42.0-67.9%) and 76.1% (95% CI, 63.7-88.4%), respectively. Multivariate analysis revealed that endocervical adenocarcinoma, usual type, or adenosquamous carcinoma, and tumor size >4 cm had worse RFS.Conclusion:The I-SCC group had good prognosis without adjuvant therapy; therefore, adjuvant therapy may be omitted in these patients. In contrast, the I-Adeno group had poor prognosis without adjuvant therapy; therefore, adjuvant therapy should be considered in their treatment

A phase 2 study of a combined diphtheria-tetanus-acellular pertussis vaccine with a Sabin-derived inactivated poliovirus vaccine in children

Background: With the goal of global eradication of poliomyelitis due to wild-type viruses within sight, WHO now recommends that infants receive at least one dose of trivalent inactivated poliovirus vaccine (IPV) with bivalent OPV (types 1 and 3) replacing trivalent OPV. Limited manufacturing capacity and new regulations on manufacturers’ use of wild-type viruses is driving the development of IPV based on attenuated Sabin type polioviruses. Takeda are developing a Sabin-based IPV (sIPV) to augment global capacity and supply. Methods: This study was performed to evaluate three dosages (low, medium and high) of the sIPV when administered as a combination vaccine with diphtheria-tetanus-acellular pertussis antigens (DTaP-sIPV) as a three dose primary series or as booster dose in Japanese infants and toddlers. Results: All formulations were immunogenic and well-tolerated with no safety concerns in either infants or toddlers. There was a dosage-dependent induction of neutralizing antibodies against Sabin polioviruses, the only statistically significant differences being between the low-dose and medium- and high-dose sIPVs. There was good correlation of neutralizing antibodies against Sabin and wild-type polioviruses. No sIPV dose had an observable effect on immune responses to DTaP components or the reactogenicity profile of the combined vaccine. Conclusion: When administered as a DTaP-sIPV combination, Takeda’s sIPV vaccine was well-tolerated and highly immunogenic in infant and toddler schedules. The medium-dose formulation offers the optimal balance between immunogenicity and potential dose-sparing to provide a new source of sIPV to enhance the global supply, while mitigating the environmental risks associated with manufacturing vaccines with wild-type viruses

Perturbing the consistency of auditory feedback in speech

Sensory information, including auditory feedback, is used by talkers to maintain fluent speech articulation. Current models of speech motor control posit that speakers continually adjust their motor commands based on discrepancies between the sensory predictions made by a forward model and the sensory consequences of their speech movements. Here, in two within-subject design experiments, we used a real-time formant manipulation system to explore how reliant speech articulation is on the accuracy or predictability of auditory feedback information. This involved introducing random formant perturbations during vowel production that varied systematically in their spatial location in formant space (Experiment 1) and temporal consistency (Experiment 2). Our results indicate that, on average, speakers’ responses to auditory feedback manipulations varied based on the relevance and degree of the error that was introduced in the various feedback conditions. In Experiment 1, speakers’ average production was not reliably influenced by random perturbations that were introduced every utterance to the first (F1) and second (F2) formants in various locations of formant space that had an overall average of 0 Hz. However, when perturbations were applied that had a mean of +100 Hz in F1 and −125 Hz in F2, speakers demonstrated reliable compensatory responses that reflected the average magnitude of the applied perturbations. In Experiment 2, speakers did not significantly compensate for perturbations of varying magnitudes that were held constant for one and three trials at a time. Speakers’ average productions did, however, significantly deviate from a control condition when perturbations were held constant for six trials. Within the context of these conditions, our findings provide evidence that the control of speech movements is, at least in part, dependent upon the reliability and stability of the sensory information that it receives over time