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PubMed2006

Spectroscopic spectral-domain optical coherence microscopy.

The spectroscopic content within optical coherence tomography (OCT) data can provide a wealth of information. Spectroscopic OCT methods are frequently limited by time-frequency trade-offs that limit high spectral and spatial resolution simultaneously. We present spectroscopic spectral-domain optical coherence microscopy performed with a multimodality microscope. Restricting the spatial extent of the signal by using high-numerical-aperture optics makes high-resolution spectroscopic information accessible, facilitated with spectral-domain detection. Simultaneous acquisition of multiphoton microscopy images is used to validate tissue structure and localization of nuclei within individual cells.

Animals↗
PubMed2006

Multidisciplinary therapy of locally far-advanced or inflammatory breast cancer with fixed perioperative sequence of epirubicin, vinorelbine, and Fluorouracil chemotherapy, surgery, and radiotherapy: long-term results.

BACKGROUND: Based on phase II data in advanced breast cancer (BC), the fluorouracil, epirubicin, and vinorelbine (FEN) combination was assessed as perioperative chemotherapy, integrated in a multidisciplinary treatment for locally advanced BC. PATIENTS AND METHODS: Patients with newly diagnosed inoperable (stage IIIB or inflammatory) BC. Multimodality treatment protocol consisted of four preoperative courses of fluorouracil (600 mg/m(2) day 1), epirubicin (75 mg/m(2) day 1), and vinorelbine (25 mg/m(2) day1 and day 8), all i.v. every 21 days, followed by radical or conservative surgery according to clinical response and four postoperative identical chemotherapy courses aimed to eradicate micrometastatic disease. Locoregional radiotherapy was offered to all patients after the completion of chemotherapy followed by hormonotherapy according to hormone receptor status. The primary end points of the study were: (a) clinical and pathological response, (b) downstaging and conversion to operable disease, and (c) recurrence-free survival (RFS) and overall survival (OS). RESULTS: Forty-eight women, one stage IIIA, 27 (56.2%) stage IIIB, two stage IIIC (4.1%), and 12 (25%) with inflammatory BC, aged 34-75 years (median, 52), were accrued. Thirty-eight and 34 patients completed the planned pre- and postoperative chemotherapy, respectively. Totals of 175 and 135 cycles were administered pre- and postoperatively, respectively. Toxicity of both phases, mainly hematologic, was in general acceptable without treatment-related death. Venous reactions were a frequent problem. All but three tumors were converted to operable, 31.3% with breast conservation. The clinical response rate (RR) was 77.7% (22.2% complete) and pathological RR was 73.3% (complete, 20% in both primary and axilla). After a median follow-up of 72 months, 62.5% and 16.7% of patients remain relapse free at 3 and 5 years, respectively, while 83% and 58.3% were alive 3 and 5 years, respectively, after the start of chemotherapy. Median RFS and OS have not yet been reached, and are currently 37+ and 62+ months, respectively. CONCLUSION: This fixed number of FEN perioperative courses schedule followed by radiotherapy is safe and highly active in inducing both local and distant control of locally far-advanced BC. This strategy is at least not inferior to other established regimens or strategies for locally far-advanced BC, while the integration of taxanes or new targeted agents may help show its true value for this challenging clinical entity.

Adult↗
PubMedDate not supplied

Helping new graduates succeed at the NCLEX-RN experience: evaluation of an anxiety-reducing workshop.

A descriptive, longitudinal study was conducted to determine the effectiveness of a 2-day workshop designed to reduce the anxiety levels of new graduates participating in the NCLEX-RN examination. A hospital nurse administrator, in collaboration with nurse educators, provided a multimodal in-service program. "Test wiseness," or test-taking strategies, and exercises related to physical and emotional well-being, were included for three groups of new graduates. Using Zung's Self-rating Anxiety Scale to collect data, reduction in anxiety after the workshop and at the completion of the NCLEX-RN experience was identified. All participants in the program passed the NCLEX-RN examination.

Anxiety↗
PubMed1995

Prospective multimodality treatment of SCLC--experience during the past 18 years.

Lung cancer has been one of the leading malignancies in China. Since 1989 it has ranked first among common malignancies in the male population, and second in females. In 1975, a multimodality treatment study group for lung cancer was organized in our institute. The group has since expanded to 15 institutions in the Beijing and Tianjin area during the past four years. The present communication is based on our experiences and data, and tries to explain the treatment strategy of our study group.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Second malignant neoplasms in long-term survivors of childhood rhabdomyosarcoma.

BACKGROUND: The occurrence of second malignant neoplasms (SMNs) in successfully treated pediatric patients with cancer has been an area of increasing concern because survival of these patients has improved with intensification of therapy. Therefore, the incidence of SMNs in long term survivors of childhood rhabdomyosarcoma (RMS) was studied. METHODS: From 1970 to 1989, 210 newly diagnosed patients (median age, 9.7 years; range, 1 month to 27 years) with RMS were treated at Memorial Sloan-Kettering Cancer Center (New York, NY). Multimodality treatment included chemotherapy, surgery, and radiotherapy, when indicated. There were 130 long term survivors (> 2 years off therapy) with a median follow-up of 9 years (range, 2-20 years). The cumulative dose of each chemotherapeutic agent and the radiation doses each patient received were reviewed. Statistical analysis was performed by comparison with the Connecticut Tumor Registry data. RESULTS: Seven patients developed a SMN, including three with acute nonlymphoblastic leukemia (ANLL) and four with solid tumors. Acute nonlymphoblastic leukemia developed a median of 4.5 years after diagnosis. Of the solid tumors, 3 developed within the radiation field at a median of 10 years after diagnosis, whereas the fourth occurred 9.3 years after initial diagnosis in a patient who did not receive radiotherapy. All seven patients with SMNs received total dactinomycin doses higher than the median (9.6 mg/M2) for the group. All three patients with ANLL received total cyclophosphamide doses higher than the median (16.8 g/M2). Moreover, six of the seven patients received a dose of radiotherapy greater than 4000 cGy. The standardized incidence ratio was: 17.07 (95% confidence interval, 6.68-35.18; P < 0.0001). CONCLUSIONS: Multimodality therapy has improved long term survival for patients with childhood RMS. The combination of high dose radiotherapy and chemotherapy appears to increase the risk for developing a second malignancy.

Adolescent↗
PubMed2001

Audio-visual perception of sinewave speech in an adult cochlear implant user: a case study.

OBJECTIVE: The purpose of this case study was to investigate multimodal perceptual coherence in speech perception in an exceptionally good postlingually deafened cochlear implant user. His ability to perceive sinewave replicas of spoken sentences, and the extent to which he integrated sensory information from multimodal sources was compared with a group of adult normal-hearing listeners to determine the contribution of natural auditory quality in the use of electrocochlear stimulation. DESIGN: The patient, "Mr. S," transcribed sinewave sentences of natural speech under audio-only (AO), visual-only (VO), and audio-visual (A+V) conditions. His performance was compared with the data collected from 25 normal-hearing adults. RESULTS: Although normal-hearing participants performed better than Mr. S for AO sentences (65% versus 53% syllables correct), Mr. S was superior for VO sentences (43% versus 18%). For A+V sentences, Mr. S's performance was comparable with the normal-hearing group (90% versus 86%). An estimate of the amount of visual enhancement, R, obtained from seeing the talker's face showed that Mr. S derived a larger gain from the additional visual information than the normal-hearing controls (78% versus 59%). CONCLUSIONS: The findings from this case study of an exceptionally good cochlear implant user suggest that he is perceiving the sinewave sentences on the basis of coherent variation from multimodal sensory inputs, and not on the basis of lipreading ability alone. Electrocochlear stimulation is evidently useful in multimodal contexts because it preserves dynamic speech-like variation, despite the absence of speech-like auditory qualities.

Adult↗
PubMed1998

Effects of combined treatment of chemotherapeutics and hyperthermia on survival and the regulation of heat shock proteins in Dunning R3327 prostate carcinoma cells.

BACKGROUND: Hyperthermia can enhance the clinical response of chemotherapeutic agents in prostate cancer, but optimal sequencing of this combination therapy needs to be developed. Given the role of heat shock proteins (HSPs) in the development of resistance (thermotolerance) to subsequent hyperthermic stresses as well as to certain chemotherapeutics, the study of HSP regulation is important in the establishment of effective schedules in multimodal treatment strategies. METHODS: In this study we evaluated the effects of the chemotherapeutic agents cisplatin, 5-fluorouracil, and adriamycin in combination with hyperthermia. (43 degrees C, 1 h) on clonogenic survival and inducible HSP70 regulation in Dunning rat adenocarcinoma of the prostate. HSP70 was analyzed by Western blot and by measuring beta-galactosidase produced by cells stably transfected with a gene construct containing the E. coli beta-galactosidase gene driven by the Drosophila HSP70 promoter. RESULTS: Colony formation assays revealed a sensitizing effect of hyperthermia when simultaneously combined with each chemotherapeutic agent, resulting in a potentiated cytotoxicity compared to subsequenced treatments. Thermotolerant cells showed a significantly better survival when treated with adriamycin alone, but also when each chemotherapeutic agent was combined with hyperthermia. This enhanced survival was correlated with inducible HSP70 accumulation. The chemotherapeutics modified the HSP70 promoter activation induced by hyperthermia, suggesting changes in the development of cellular thermotolerance. CONCLUSIONS: Our data reveal synergistic cytotoxic effects of the synchronous application of chemotherapeutic agents and hyperthermia on this model of prostate cancer. Furthermore, they demonstrate that the induction of HSPs in thermotolerant cells, as measured by HSP70 induction, results in a modulation the chemotherapeutic-mediated cytotoxicity. Therefore, HSP70 is a useful marker of cellular resistance in multimodal approaches combining hyperthermia and chemotherapeutic agents in the treatment of locally advanced prostate carcinoma.

Animals↗
PubMed2006

Endometrial cancer in Kentucky: the impact of age, smoking status, and rural residence.

INTRODUCTION: The study objectives were to assess the effect of age, to evaluate the impact of smoking, and to determine the effect of rural residence on tumor characteristics, treatment modalities, and outcomes for Kentucky's endometrial cancer patients. METHODS: The Kentucky Cancer Registry identified Kentucky residents diagnosed with endometrial cancer from 1995 to 2002. Data abstracted included demographics, tumor characteristics, treatment, and recurrence/survival status. RESULTS: Three thousand five hundred and sixty-two women were diagnosed with endometrial cancer. Mean age at diagnosis decreased significantly (P=0.0388) over the 7-year period. Smokers had higher grade, stage, and worse outcomes. Rural women more often lacked commercial insurance, underwent less comprehensive surgical evaluation, and had less multimodality treatment. Increasing age (P<0.0001), positive or unknown smoking status (P=0.0003), black race (P<0.0001), no commercial insurance (P<0.0001), increasing grade or advanced stage (P<0.0001), small size of treating hospital (P<0.0001), and unknown nodal status (P<0.0001) were negatively associated with disease-specific survival. Lymph node sampling was performed in only 38.6% of women. On multivariate analysis, age (RR 1.38 for 10 year increments; P<0.0001), smoking (RR 1.38; P=0.008), no commercial insurance or Medicaid (RR 1.87; P=0.0007), rural residence (RR 0.77; P=0.011), advanced stage and grade (RR 7.96, 3.96; P<0.0001), and no nodal evaluation or unknown nodal status (RR 2.32, 2.51; P<0.0001) significantly effected disease-specific survival. CONCLUSIONS: Our data support a trend toward a younger age for endometrial cancer diagnosis, confirm the adverse impact of smoking and socioeconomic factors, and demonstrate an association between incomplete surgical staging and decreased survival.

Adult↗
PubMed2003

The associative striatum: organization of cortical projections to the dorsocentral striatum in rats.

The dorsocentral striatum (DCS) is the major site of input from medial agranular cortex (AGm) and has been implicated as an associative striatal area that is part of a cortical-subcortical circuit involved in multimodal spatial functions involving directed attention. Anterograde axonal tracing was used to investigate the spatial organization of corticostriatal projections to DCS. Injections of biotinylated dextran amine were made into several cortical areas known to project to DCS based on retrograde tracing data. These included areas AGm, lateral agranular cortex (AGl), orbital cortex, posterior parietal cortex (PPC), and visual association cortex. We discovered a previously undescribed geometry whereby the projection from AGm is prominent within DCS and the main corticostriatal projections from areas other than AGm are situated around the periphery of DCS: visual association cortex dorsomedially, PPC dorsally, AGl laterally, and orbital cortex ventrally. Each of these cortical projections is also represented by less dense aggregates of terminal labeling within DCS, organized as focal patches and more diffuse labeling. Because these cortical areas are linked by corticocortical connections, the present findings indicate that interconnected cortical areas have convergent terminal fields in the region of DCS. These findings suggest that DCS is a central associative region of the dorsal striatum characterized by a high degree of corticostriatal convergence.

Animals↗
PubMed1997

[Fear-avoidance-beliefs in patients with backpain].

INTRODUCTION: In recent years most industrialized nations have been confronted with a dramatic increase in cases dealing with back pain which, because of the associated costs, has put a strain on health care systems. Because of the tremendous costs caused by patients with chronic illnesses, there is a common interest in identifying determinants responsible for the pain becoming chronic. According to the fear-avoidance model, chronic back pain is the cause of specific patient beliefs according to their perception and appraisal of back pain and their assumptions about the connection between pain and work activities. These fear-avoidance beliefs are assumed as the main cognitive factors of adapting to chronic invalidism. In this study a German version of a self-reporting instrument that assesses fear-avoidance beliefs (FABQ, Waddell et al. 1993) is presented. METHODS: A translated version of the "Fear-Avoidance Beliefs Questionnaire" was given to 87 patients with back pain, who took part in a multimodal treatment program in an outpatient pain unit. The questionnaire was administered at different times in the therapeutic process. We examined the factor structure of the questionnaire and conducted the first examinations concerning its psychometric properties. RESULTS: The results of our data set concerning different aspects of reliability and validity conform the good psychometric properties of the questionnaire. The factor analysis revealed a three-factor solution, which accounted for nearly 60% of the variance. The first factor made up 34% of the variance. The six corresponding items dealt with "back pain caused by work". The second factor made up 13% of the variance. The content of the 5 items is focused on the patients' view about his/her probable return to work. Beliefs about physical activity in back pain (factor 3, 5 items) accounted for 12% of the variance. Correlation analysis demonstrated that all three factors are of independent value, which showed satisfactory reliability. Furthermore, we analyzed the prognostic value of the three factor dimensions. Patients completed multidisciplinary treatment according to the concept of "functional restoration". At the end of treatment, factor 1 (causation by work) was not diminished, but both other factors showed significant reductions. In a discriminant factor analysis, back-to-work could be significantly predicted by factor 3 (beliefs about physical activity) and factor 2 (patients' prognosis about their probable return to work at the beginning of treatment). Furthermore, length of time off work and age accounted for an additive classification rate of 77%. The FABfactor 1 (causation by work) was of no predictive value. CONCLUSIONS: The results suggest that primary target points for further investigation include an analysis of the patients' beliefs about their pain, with special emphasis on fear-avoidance beliefs. It is also necessary to analyze the behavioral assumptions of the fear-avoidance model in an experimental design. Furthermore, our results concerning the psychometric properties of the questionnaire should be proved in a far larger sample of back pain patients.

English Abstract↗
PubMed1995

Impact of clinicopathologic parameters on patient survival in carcinoma of the cervical esophagus.

BACKGROUND: The survival of patients with carcinoma of the cervical esophagus remains poor in spite of multimodality treatment and technical improvements in surgical resection and reconstruction. This study was undertaken to update our experience with cervical esophageal carcinoma and to identify factors that had an impact on patient survival and quality of life. PATIENTS AND METHODS: Clinical data encompassing 132 variables were collected on 67 patients with cervical esophageal carcinoma from 1980 to 1993. Statistical analysis was performed: independent Student's t-tests, Cox regression, Kaplan-Meier curves, and log rank analyses were used in the statistical evaluation. The mean age of the patients was 63 years (range 31 to 88). Dysphagia was the primary symptom in 86% of patients; 80% had received no prior treatment. The most common abnormal finding (21%) on physical examination was a neck mass. RESULTS: Curative resection was performed in 22 patients, 7 had palliative procedures, and 7 were found to be inoperable at exploration and received palliative treatment. Radiation with or without chemotherapy was definitive treatment for 10 patients, whereas 4 patients were treated with chemotherapy alone for cure, and 17 patients received palliative treatment. The mean survival following diagnosis was 17 months (range 1 to 96). Cumulative 5-year survival was 12%. CONCLUSIONS: Persistent disease, chemotherapy prior to presentation, and chemotherapy for cure remained as statistically significant parameters associated with decreased survival by multivariate analysis. There was a trend toward improved survival in patients treated with surgical resection.

Adult↗
PubMedDate not supplied

Chemical composition distribution of bacterial copolyesters.

Poly(3-hydroxybutyrate) [P(3HB)] and its copolymers with hydroxyalkanoates are naturally occurring thermoplastic materials produced by bacteria. There are many potential uses for these copolyesters owing to their biodegradability and biocompatibility. The physical properties of the copolyesters vary depending on the chemical structure as well as the composition of the comonomers. Usually, we expect, copolymers to have a narrow chemical composition distribution (CCD). Several reports, however, have pointed out that some bacterial copolyesters have broad and/or multimodal CCD. Fractionation based on the chemical composition has also been reported for several bacterial copolyester samples. In this review, the literature concerning CCD and fractionation based on chemical composition is summarized. The width of CCD is approximated based on the data of diad sequence distribution. Generality of the complex CCD in bacterial copolyesters is also discussed.

Bacteria↗
PubMed1995

Combined carboplatin plus bleomycin and conventional radiotherapy for advanced carcinomas of the head and neck.

In a previous study, we reported a 72% response rate (CR = 52%) in patients with unresectable head and neck (H&N) carcinomas treated with simultaneous carboplatin (CBDCA) and radiotherapy (RT). Bleomycin (Bleo), a known radiosensitizing agent, has been shown to increase response rates when given together with RT in similar patients. To explore the nonoverlapping toxicities of these two agents, we combined i.v. CBDCA (100 mg/m2/week), Bleo (5 units on day 1 and 4/weekly) and standard doses of RT in patients with unresectable H&N carcinomas. Chemotherapy (CT) was continued until completion of RT. Twenty-three (13 males, 10 females) previously untreated patients with stage IV squamous cell carcinoma of the H&N were treated at the University of Maryland Medical Center: 61% had oropharyngeal cancers; 26%, hypopharynx; 9%, oral cavity; and 4%, an unknown primary. Moderate to severe mucositis developed in 90%, which required RT interruptions of up to 3 weeks. After a median follow-up (FU) of 18 months, 35% achieved a complete response (CR) and 65% died from progressive disease. These preliminary data suggest that the addition of Bleo increases mucosal toxicity substantially and, while a moderate response rate was observed, it is unlikely that the CR rate will be higher than CBDCA/RT, which was also better tolerated and hence more suitable to multimodal approaches.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Behavioural-communications treatment of marital interaction: negative behaviours.

The present investigation assessed the effectiveness of a behavioural-communications marital intervention package focused solely upon negative behaviours. Treatment effectiveness was evaluated via two independent, within-subject multiple base-line designs. Four target behaviours, selected on the basis of clinical and laboratory assessment, were sequentially and cumulatively introduced over the course of an eight-week treatment programme. Multimodal assessment techniques included self-report, spouse-report, and direct observations of laboratory-based interactions. While slight differences occurred between measurement systems, all results attested to the efficacy of the therapeutic package. One-year follow-up data continued to indicate maintenance of treatment gains over time. These findings were discussed with regard to decelerative targets of intervention, and recommendations were made for continued investigations in the area.

Adult↗
PubMed2002

The stroke patient who woke up: clinical and radiological features, including diffusion and perfusion MRI.

BACKGROUND AND PURPOSE: Time of stroke onset is uncertain for patients who wake from sleep with stroke. Functional imaging techniques may allow estimation of benefit and risk of acute stroke therapy. We compared the clinical and multimodal MRI findings of patients with uncertain stroke onset with those with known onset time. METHODS: Patients imaged within 24 hours of ischemic stroke onset between January 1997 and June 2000 were identified from a prospective stroke registry. Clinical and imaging data from patients with known stroke onset (group I) were compared with those who woke with stroke (group II). RESULTS: A total of 364 patients were identified, of whom 100 (27%) woke from sleep with stroke. Group I and group II did not differ in age, gender, National Institutes of Health Stroke Scale, or TOAST (Trial of Org 10172 in Acute Stroke Treatment) diagnoses. Time from stroke onset was shorter in group I (mean 6.0 versus 13.3 hours, P<0.001); time from detection did not differ between groups (6.0 versus 5.9 hours). Within 3 hours, diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) lesion volumes were similar in both groups; DWI-PWI mismatch was present in 82% of group I and 73% of group II patients. Mean apparent diffusion coefficient of water (ADC) of group I patients was negatively associated with DWI volume (beta=-0.324, P=0.004) and time from stroke onset (beta=-0.238, P=0.031) in multivariate analysis. The mean ADC of group II patients was lower than that of group I patients within 3 hours of stroke detection (mean 556 versus 665 microm2/s, P<0.01), but individual group II patients had ADC values as high as 742 microm2/s, in addition to a DWI-PWI mismatch pattern. CONCLUSIONS: Onset time is uncertain in over one quarter of acute ischemic stroke patients. Clinical features of these patients do not differ significantly from those with known onset time. Some patients who wake with stroke seem to have favorable imaging characteristics for acute stroke therapy. Further study is needed to determine whether criteria for therapy based on imaging parameters can safely be applied to these patients.

Aged↗
PubMedDate not supplied

[Monitoring of brain damage in patients with head injuries].

INTRODUCTION: Early detection of impending cerebral ischemia in comatose patients is most important to avoid secondary insults to the injured brain. DEVELOPMENT: Whilst the computer tomography scan provides a static picture primarily concerned with details of structure, the electroencephalogram (EEG) is the objective source par excellence of information about brain function. The EEG represents the only biological activity suitable for continuous non-invasive monitoring of brain function. In this context, the cerebral function monitor (CFM) of Maynard and Prior (1969) provides a compressed array of amplitude variations and has benefited many critical patients. Among the invasive methods, direct monitoring of cerebral white matter oxygenation (tissular pressure of oxygen) is a promising new technique that has attracted considerable interest over the past four years. Recent studies on multimodal hemodynamic monitoring (intracranial pressure, cerebral perfusion pressure, PtiO2), place this latter technique as a primary basis for management decisions in the ICUs. We have studied four young injured patients, to compare early digital EEG recordings with tissular pressure of oxygen data. CONCLUSIONS: In general, there was agreement between EEG findings and tissular pressure of oxygen levels. The EEG helped with urgent data, though barbiturate therapy interfered in two cases.

Brain↗
PubMed2004

Survival and prognostic factors in resected cN2-pN0 non-small cell lung cancer.

This study retrospectively examined the records of patients with clinical N2 (cN2) stage non-small cell lung cancer (NSCLC) who were surgically treated but who actually had pathologic N0 (pN0) stage disease. From 1982 to 1997, 94 patients with cN2 NSCLC underwent surgery. Forty-five patients proved to have pN0 disease, with an overall 5-year survival rate of 67.3%. According to the Cox model, visceral pleural invasion (p=0.01) and a carcinoembryonic antigen (CEA) concentration > or =2.5 ng/mL (p=0.03) negatively influenced survival. The six patients with both visceral pleural involvement and a CEA > or =2.5 ng/mL all died within five years compared with a 78.1% 5-year survival for the 21 patients who had neither factor. For the subgroup of patients who have poor prognostic factors, multimodality therapy should be considered. Our previous report found that parietal pleural invasion, elevated CEA concentration, and the number of involved mediastinal lymph node (MLN) stations correlated with survival in 40 patients with cN2-pN2 disease who underwent resection. These data show how important it is to assess pleural status carefully and measure the CEA concentration, as is to determine the MLN status in patients with cN2 disease.

Aged↗
PubMed2004

[The fibromyalgia syndrome].

The Fibromyalgia Syndrome Fibromyalgia is a "pain disorder" and is diagnosed in accordance with the criteria of the American College of Rheumatology. The clinical presentation involves a complexity of symptoms with pains occurring at numerous sites identified by "tender points", disturbed sleep, increased fatigue, and numerous psychovegetative and psychic symptoms. Epidemiological data reveal high prevalence figures for fibromyalgia, and the disease is usually chronic. The etiopathogenesis can be described only within a multifactorial model. Numerous neurobiological and psychosocial factors militate in favor of a central disturbance of stress coping and pain perception. Multimode therapeutic approaches need to be individualized, but in many cases continue to be only moderately successful.

Adult↗