Cautionary Findings Research Articles

Temporary reduction of distortion product otoacoustic emissions (DPOAEs) immediately following auditory brainstem response (ABR)

The hearing status of an experimental animal is typically assessed in the laboratory setting by the combined use of auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs), carried out in succession, with the former assay preceding the latter. This study reports a cautionary finding that the use of this accepted regimen yields a reduced DPOAE response. When the DPOAEs were performed after ABR testing, transient reduction of the DPOAE amplitudes was observed at all frequencies in both the inbred, C57/B6 and FVB/N, and the outbred, SW mouse strains. DPOAEs were reduced post-ABR in multiple mouse strains which suggests that this finding is not strain-specific but a general consequence of the preceding ABR analysis. The reduction in DPOAE was temporary: when re-tested at one hour, DPOAE amplitudes recovered to pre-ABR levels. In contrast to the ABR’s impact on DPOAE response, ABR thresholds were not altered or reduced when preceded immediately by DPOAE measurements. The molecular alterations underlying the ABR-induced transient reduction of DPOAE remain to be determined. To investigate the potential role of reactive oxygen species in post-ABR DPOAE reduction, transgenic mice over-expressing SOD1, the cytoplasmic enzyme critical for removal of superoxide radicals were subjected to the same auditory testing regimen. Similar to their wild type littermates, the SOD1 transgenic mice also demonstrated post-ABR DPOAE reduction, and thus do not support a role for superoxide radicals in transient reduction of DPOAE. While toxic noise exposure is known to negatively impact OAE, transient decrease in DPOAE levels following standard ABR assay has not been previously described. A practical outcome from this study is a recommendation for reversal of the traditional order for carrying out auditory tests, with the OAE measurements preceding ABR assessment, thus ensuring that the DPOAE response is unaffected.

Managing Delegated Search Over Design Spaces

Organizations increasingly seek solutions to their open-ended design problems by employing a contest approach in which search over a solution space is delegated to outside agents. We study this new class of problems, which are costly to specify, pose credibility issues for the focal firm, and require finely tuned awards for meeting the firm's needs. Through an analytical model, we examine the relationship between problem specification, award structure, and breadth of solution space searched by outside agents toward characterizing how a firm should effectively manage such open-ended design contests. Our results independently establish and offer a causal explanation for an interesting phenomenon observed in design contests—clustering of searchers in specific regions of the solution space. The analysis also yields a cautionary finding—although the breadth of search increases with number of searchers, the relationship is strongly sublinear (logarithmic). Finally, from the practical perspective of managing the delegated search process, our results offer rules of thumb on how many and what size awards should be offered, as well as the extent to which firms should undertake problem specification, contingent on the nature (open-endedness and uncertainty) of the design problem solution being delegated to outside agents. This paper was accepted by Kamalini Ramdas, entrepreneurship and innovation.

The Deflation-Based FastICA Estimator: Statistical Analysis Revisited

This paper provides a rigorous statistical analysis of the deflation-based FastICA estimator, where the independent components (ICs) are extracted sequentially. The focus is on two aspects of the estimator: robustness against outliers as measured by the influence function (IF) and on its asymptotic relative efficiency (ARE) as measured by the ratio of the asymptotic variance of the FastICA w.r.t. the optimal maximum likelihood estimator (MLE). The derived compact closed-form expression of the IF reveals the vulnerability of the FastICA estimator to outliers regardless of the used nonlinearity. A cautionary finding is that even a moderate observation towards certain directions can render the estimator deficient in the sense that its separation performance degrades worse than a plain guess. The IF allows the derivation of a compact closed-form expression for the asymptotic covariance matrix of the FastICA estimator and subsequently its asymptotic relative efficiencies (AREs). The ARE figures calculated for some selected source distributions illustrate the fact that the order which the ICs are found is crucial as the accuracy of the previously extracted components can dominantly affect the accuracy of the successive deflation stages.

Managing Delegated Search Over Design Spaces

Organizations increasingly seek solutions to their open-ended design problems by employing a contest approach in which search over a solution space is delegated to outside agents. We study this new class of problems, which are costly to specify, pose credibility issues for the focal firm, and require finely-tuned awards for meeting the firm's needs. Through an analytical model, we examine the relationship between problem specification, award structure, and breadth of solution space searched by outside agents towards characterizing how a firm should effectively manage such open-ended design contests.Our results independently establish and offer a causal explanation for an interesting phenomenon observed in design contests - clustering of searchers in specific regions of the solution space. The analysis also yields a cautionary finding - while the breadth of search increases with number of searchers, the relationship is strongly sub-linear (logarithmic). Finally, from the practical perspective of managing the delegated search process, our results offer rules of thumb on how many and what size awards should be offered, as well as the extent to which firms should undertake problem specification, contingent on the nature (open-endedness and uncertainty) of the design problem solution being delegated to outside agents.

Transgastric Organ Resection Solely with the Prototype R Scope and the Self-Approximating Translumenal Access Technique (STAT)

Background: The Self-Approximating Translumenal Access Technique (STAT) has been demonstrated to provide safe translumenal access, a reliable means of closure and in-line endoscope positioning to target abdominal organs during NOTES. To date, organ resection with NOTES has typically required percutaneous assistance. We hypothesized that the in-line positioning and partial stability provided by STAT would allow single access NOTES procedures if a multiarticulated endoscope could be used. Methods: 19 pigs (av wt 32 kg) underwent NOTES (7 cholecystectomy and 14 uterine horn resections). STAT was used as previously described using a prototype R-scope (Olympus) with 2 articulated channels opposed at 90°. For pelvic access, a short tunnel was used and for cholecystectomy a rightward tunnel crossing the greater curve was made. A serotomy was then made using an IT-knife to prevent injury to adjacent organs. The gallbladder was dissected fundus down and hemoclips and a detachable loop were placed on the cystic duct and artery before removal. Operative and clinical data was collected and all procedures were digitally recorded. After a 2-3 week observation period, animals were euthanized and necropsy performed for documentation of gross findings. Results: The mean operative time was 3.6 hrs (range 1.6-5.5), the mean mucosal incision to serotomy time was 37 min (26-78), mean tunnel length was 11cm (6-23) and width 4cm (2.5-5). The R-scope allowed significant counter traction and visibility during the procedures and all target organs were successfully resected without laparoscopic assistance. Significant operative complications: 1 STAT tunnel failure during extraction of an 8x3cm standard specimen, 2 perforations (1 due to a prototype duodenal occlusion device and 1 due to enterotomy during cholecystectomy, 1 entrapment of small bowel with an endoloop. Post-operative: All animals gained weight appropriately with 1 sacrificed POD 12 due to lethargy (cystic duct leak and biloma). Necropsy findings were significant for healed STAT tunnels without complications, minor adhesions (5), bile leaks (2), lap port abscess (1) and ventral hernia (1). Conclusions: The combination of the R-scope and STAT allows effective, single site NOTES procedures using currently available devices. The study highlights two cautionary findings: it is possible to tear a submucosal tunnel with excessive torquing of the scope during the procedure, and while the R-scope provides improved tissue manipulation and the ability to apply counter traction, the complications incurred here suggest further improvements in technique and technology will be required for safe and effective NOTES procedures.

Medical cost analysis: Application to colorectal cancer data from the SEER Medicare database

Incompleteness is a key feature of most survival data. Numerous well established statistical methodologies and algorithms exist for analyzing life or failure time data. However, induced censorship invalidates the use of those standard analytic tools for some survival-type data such as medical costs. In this paper, some valid methods currently available for analyzing censored medical cost data are reviewed. Some cautionary findings under different assumptions are envisioned through application to medical costs from colorectal cancer patients. Cost analysis should be suitably planned and carefully interpreted under various meaningful scenarios even with judiciously selected statistical methods. This approach would be greatly helpful to policy makers who seek to prioritize health care expenditures and to assess the elements of resource use.

Cryo-Ablation for Septal Tachycardia Substrates in Pediatric Patients

Craniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage.MISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18–80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770.Between Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7–22.6] vs eight [14·8%, 6·6–27·1], p=0·542), 7 day mortality (zero [0%, 0–8·4] vs one [1·9%, 0·1–9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1–12·6] vs five [9·3%, 3·1–20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1–12·6] vs zero [0%, 0–6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0–35·6] vs three [7·1%; 1·5–19·5]; p=0·051).MIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage.National Institute of Neurological Disorders and Stroke, Genentech, and Codman.

The construct validity of three entry level personality inventories used in the UK: cautionary findings from a multiple‐inventory investigation

This paper reports psychometric analyses into the convergent and divergent validity of three popular entry‐level measures of occupational personality in the UK and Continental Europe. A sample of 504 individuals completed all three measures: the British version of the Hogan Personality Inventory (HPI), the Occupational Personality Questionnaire (OPQ Version FS5.2), and the Business Personality Indicator (BPI). In addition, independent ratings of the conceptual loading of primary source scales onto the Five Factor Model (FFM) were obtained (n = 66). Data were used in a three‐stage analytical procedure directed at examining psychometric and construct validity. Results are reported for descriptive statistics (means, standard deviations, Cohen's d), internal consistency reliability (Cronbach's alphas), and exploratory factor analyses. Findings into the construct validity of first‐order scales (i.e. primary source scales) and second‐order scales (i.e. FFM loadings) are presented in detail, including multitrait–multimethod (MTMM) analyses of convergent and divergent validity. For some scales, the observed variability in our sample suggested significant range restriction/enhancement. It was found that scale reliabilities were generally lower than those typically reported by the test publishers, and that published factor structures for these measures could not be replicated by the authors for this sample of individuals. Further independent construct validity research into occupational personality inventories is encouraged based upon our proposed model of single‐, dual‐, and multiple‐inventory construct validation studies. Practically, our findings suggest that when IWO psychologists or personnel professionals aim to select/screen job applicants for a particular personality trait those who are selected may vary depending on (i) which personality inventory is used, (ii) the actual variability in the applicant sample tested, and (iii) reliability of the scales under consideration. As such, this study sounds a note of caution. Future research is called for to replicate these findings. Copyright © 2003 John Wiley & Sons, Ltd.

It Doesn't Matter: Some Cautionary Findings About Sex and Representation From School Committee Conversations

One of the most important findings in the field of gender and politics is that women elected officials at the state and national levels do a better job than men of representing the interests of women, children, and families. This paper uses school committees to ask the same question about women elected officials at the local level. Thus the question that guides this paper is: Does it matter for women if women are elected to this local political institution? If it does matter, then we should “hear” women's distinct ways of participating through their discussions at committee meetings. The study finds, in contrast, that in this political institution women and men behave in remarkably similar ways when separated by committee roles, and that women elected officials in this political institution spend very little time addressing issues affecting girls in public education.

Creativity software and DSS: Cautionary findings

Contrary to expectations, a study of creativity enhancing software showed that user creativity declined when using the software on an analysis task. Software increased the number of alternatives, but independent judges determined that these were less original or inventive than those produced without the software. These findings were consistent for both ‘highly creative’ and ‘less creative’ groups. Computer technology is an added variable that can interact to inhibit creativity in a moderately complex case analysis task. Creativity inducing software appears to need further development before it can contribute meaningfully to improving decision support systems.