Evaluation of a new, rapid, simple test for the detection of influenza virus

BACKGROUND: Influenza virus infections are responsible for significant morbidity and mortality in both pediatric and adult populations worldwide. Rapid and accurate diagnosis of influenza is necessary for appropriate patient management during the influenza season and for optimal utilization of anti-influenza therapy. We prospectively tested the accuracy of a simple and rapid diagnostic method. METHODS: Ninety-eight samples (nasal and pharyngeal swabs) from patients with upper respiratory tract infection symptoms who presented to primary healthcare centres in Barcelona (Spain) were prospectively analyzed. The samples were collected as part of influenza surveillance program. Samples that had enough volume to make the new test after aliquoting the amount needed to perform routine tests were included. None of the samples were pre-selected as a result of their status in relation to influenza virus. Samples were analyzed by in-house real-time PCR and Alere™ i Influenza A & B (Alere™ i), which uses isothermal amplification of nucleic acids for the qualitative detection of influenza A and B in nasal swabs transported in viral transport media. The two techniques were compared by positive percent agreement (PPA) and negative percent agreement (NPA). Statistical analysis was performed with Stata. RESULTS: Of the 98 samples analysed 90 were concordant; 46 (46.9%) were positive and 44 (44.9%) were negative. Five samples showed invalid results with the Alere™ i test and could be not re-tested due to insufficient sample volume and were not included in the final statistical analysis. In the 93 remaining samples, the Alere™ i test showed 97% of accuracy having correctly classified 90 samples. We obtained discordant results in 3 samples (3%). The PPA was 93.8% for influenza A and 94.1% for influenza B, and NPA was 100% for influenza A and influenza B virus. In addition, the Alere™ i was very rapid (15 minutes or less) and extremely easy to use. CONCLUSIONS: The Alere™ i test provided a good correlation compared to the real-time PCR test for the diagnosis of influenza. Since this method can be performed in minutes, it allows immediate, accurate clinical decisions to prescribe appropriate antiviral treatment or isolation of patients

From open radical hysterectomy to robot-assisted laparoscopic radical hysterectomy for early stage cervical cancer: aspects of a single institution learning curve

We analysed the introduction of the robot-assisted laparoscopic radical hysterectomy in patients with early-stage cervical cancer with respect to patient benefits and surgeon-related aspects of a surgical learning curve. A retrospective review of the first 14 robot-assisted laparoscopic radical hysterectomies and the last 14 open radical hysterectomies in a similar clinical setting with the same surgical team was conducted. Patients were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and open radical hysterectomy (RH) before August 2006 and were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and robot-assisted laparoscopic radical hysterectomy (RALRH) after August 2006. Overall, blood loss in the open cases was significantly more compared with the robot cases. Median hospital stay after RALRH was 5 days less than after RH. The median theatre time in the learning period for the robot procedure was reduced from 9 h to less that 4 h and compared well to the 3 h and 45 min for an open procedure. Three complications occurred in the open group and one in the robot group. RALRH is feasible and of benefit to the patient with early stage cervical cancer by a reduction of blood loss and reduced hospital stay. Introduction of this new technique requires a learning curve of less than 15 cases that will reduce the operating time to a level comparable to open surgery

Patient-Derived Models of Cancer in the NCI PDMC Consortium: Selection, Pitfalls, and Practical Recommendations

For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as cancer therapeutics. Based on collective experience from the consortium groups, we provide insight regarding PDMCs established both in vitro and in vivo, with a focus on practical matters related to developing and maintaining key cancer models through a series of vignettes. Although every model has the potential to offer valuable insights, the choice of the right model should be guided by the research question. However, recognizing the inherent constraints in each model is crucial. Our objective here is to delineate the strengths and limitations of each model as established by individual vignettes. Further advances in PDMCs and the development of novel model systems will enable us to better understand human biology and improve the study of human pathology in the lab

Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer

BACKGROUND: Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. METHODS: Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. RESULTS: Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. CONCLUSION: Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed

Patients' preferences for involvement in treatment decision making in Japan

BACKGROUND: A number of previous studies have suggested that the Japanese have few opportunities to participate in medical decision-making, as a result both of entrenched physician paternalism and national characteristics of dependency and passivity. The hypothesis that Japanese patients would wish to participate in treatment decision-making if adequate information were provided, and the decision to be made was clearly identified, was tested by interview survey. METHODS: The subjects were diabetic patients at a single outpatient clinic in Kyoto. One of three case study vignettes (pneumonia, gangrene or cancer) was randomly assigned to each subject and, employing face-to-face interviews, the subjects were asked what their wishes would be as patients, for treatment information, participation in decision-making and family involvement. RESULTS: 134 patients participated in the study, representing a response rate of 90%. The overall proportions of respondents who preferred active, collaborative, and passive roles were 12%, 71%, and 17%, respectively. Respondents to the cancer vignette were less likely to prefer an active role and were more likely to prefer family involvement in decision-making compared to non-cancer vignette respondents. If a physician's recommendation conflicted with their own wishes, 60% of the respondents for each vignette answered that they would choose to respect the physician's opinion, while few respondents would give the family's preference primary importance. CONCLUSIONS: Our study suggested that a majority of Japanese patients have positive attitudes towards participation in medical decision making if they are fully informed. Physicians will give greater patient satisfaction if they respond to the desire of patients for participation in decision-making

Population dynamics and genetic connectivity in recent chimpanzee history

Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees

Local genetic adaptation to habitat in wild chimpanzees

How populations adapt to their environment is a fundamental question in biology. Yet, we know surprisingly little about this process, especially for endangered species, such as nonhuman great apes. Chimpanzees, our closest living relatives, are particularly notable because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite it having wide implications for evolutionary biology and conservation. By using newly sequenced exomes from 828 wild chimpanzees (388 postfiltering), we found evidence of fine-scale genetic adaptation to habitat, with signatures of positive selection in forest chimpanzees in the same genes underlying adaptation to malaria in humans. This work demonstrates the power of noninvasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees

Population dynamics and genetic connectivity in recent chimpanzee history

The European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 864203) (to T.M.-B.). BFU2017-86471-P (MINECO/FEDER, UE) (to T.M.-B.). “Unidad de Excelencia María de Maeztu”, funded by the AEI (CEX2018-000792-M) (to T.M.-B.). Howard Hughes International Early Career (to T.M.-B.). NIH 1R01HG010898-01A1 (to T.M.-B.). Secretaria d’Universitats i Recerca and CERCA Program del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880) (to T.M.-B.). UCL’s Wellcome Trust ISSF3 award 204841/Z/16/Z (to A.M.A. and J.M.S.). Generalitat de Catalunya (2017 SGR-1040) (to M. Llorente). Wellcome Trust Investigator Award 202802/Z/16/Z (to D.A.H.). The Pan African Program: The Cultured Chimpanzee (PanAf) is generously funded by the Max Planck Society, the Max Planck Society Innovation Fund, and the Heinz L. Krekeler Foundation.Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees.Publisher PDFPeer reviewe

A comparison of scopolamine and biperiden as a rodent model for cholinergic cognitive impairment

RATIONALE: The nonselective muscarinic antagonist scopolamine hydrobromide (SCOP) is employed as the gold standard for inducing memory impairments in healthy humans and animals. However, its use remains controversial due to the wide spectrum of behavioral effects of this drug. OBJECTIVE: The present study investigated whether biperiden (BIP), a muscarinic m1 receptor antagonist, is to be preferred over SCOP as a pharmacological model for cholinergic memory deficits in rats. This was done by comparing the effects of SCOP and BIP using a battery of operant tasks: fixed ratio (FR5) and progressive ratio (PR10) schedules of reinforcement, an attention paradigm and delayed nonmatching to position task. RESULTS: SCOP induced diffuse behavioral disruption, which included sensorimotor responding (FR5, 0.3 and 1 mg/kg), food motivation (PR10, 1 mg/kg), attention (0.3 mg/kg, independent of stimulus duration), and short-term memory (delayed nonmatching to position (DNMTP), 0.1 and 0.3 mg/kg, delay-dependent but also impairment at the zero second delay). BIP induced relatively more selective deficits, as it slowed sensorimotor responding (FR5, 10 mg/kg) and disrupted short-term memory (DNMTP, 3 mg/kg, delay-dependent but no impairment at the zero second delay). BIP had no effect on food motivation (PR10) or attention. CONCLUSION: Muscarinic m1 antagonists should be considered an interesting alternative for SCOP as a pharmacological model for cholinergic mnemonic deficits in animals

Population dynamics and genetic connectivity in recent chimpanzee history

Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (<Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees