Biasability and reliability of expert forensic document examiners.

The performance of experts can be characterized in terms of biasability and reliability of their judgments. The current research is the first to explore the judgments of practicing forensic document experts, professionals who examine and compare disputed handwritten evidence to handwriting exemplars of individuals involved in criminal or civil litigation. Forensic handwriting experts determine if questioned and known handwritten items are of common authorship or written by different individuals, and present their findings in legal proceedings. The expert participants in our study (N=25) were not aware that they were part of a research study. Thirteen participants were led to believe that they were working on a case commissioned from the prosecution and the other twelve that it was for the defense. We did not find evidence in this study that this information biased their judgments, which may make sense since document examiners (in contrast to many other forensic domains) do not primarily work within an organizational forensic laboratory culture. The lack of bias in our findings may have been also due to the stimuli we used or/and the great variability in the judgments within each group, reflecting a lack of consistency in conclusions among examiners. A detailed discussion of our findings is presented along with the limitations that may have affected our results.

Prepared Disappearing Ink and Deciphering of Documents.

Disappearing inks can be used for forgeries in many fields. In this study, thymolphthalein indicator solution was prepared as a disappearing ink. A total of 54 different solutions containing thymolphthalein were prepared at six different concentrations and nine different pH values. Among the prepared solutions, 0.16 g/50 mL and 0.32 g/65 mL thymolphthalein at pH 14 were the optimum solutions that were not distinguishable from regular ink when applied to promissory note. Fountain pens were filled with the abovementioned ink solutions and applied to promissory notes for experimental purposes. After 40 h, ink residues were not visible on promissory notes written with the ink with the optimum pH (pH = 14) value. To decipher the entries that disappeared, an instrumental method (Video Spectral Comparator-8000) and a chemical method (using NH3 vapor) were used, succeeded at 0.32 g/65 mL, but failed at 0.16 g/50 mL thymolphthalein. Therefore, NH3 had to be sprayed for 0.16 g/50 mL with negligible harm.

An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.

This corrects the article DOI: 10.1038/bjc.2017.85.

The Whitaker Classification of Craniosynostosis Outcomes: An Assessment of Interrater Reliability.

BACKGROUND: The Whitaker classification is a simple and widely used system for describing aesthetic outcomes after craniosynostosis surgery. The purpose of this study is to evaluate its interrater reliability for patients who have undergone fronto-orbital surgery. METHODS: A retrospective review of patients with craniosynostosis who underwent surgical intervention at a tertiary referral center was conducted. Inclusion criteria were as follows: single-suture craniosynostosis, surgical intervention before age 2 years, and photographs taken before revisions between 5 and 20 years of age. Thirteen craniofacial surgeons independently reviewed the subjects' photographs and assigned Whitaker classifications. Interrater reliability was assessed with the Cohen kappa statistic. RESULTS: Twenty-nine subjects were included. Average ages at surgery and at the time of postoperative photography were 0.8 year and 12.8 years, respectively. The κ value for all 13 raters was 0.1567 (p < 0.0001), indicating "slight agreement." Pairwise comparisons demonstrated κ values ranging from 0.0384 to 0.5492. The average rating for the set of 29 photographs differed significantly across the 13 raters (p = 0.0020) and ranged from 1.79 ± 0.68 to 2.79 ± 0.77. Finally, we found that average Whitaker classification did not differ significantly between subjects who subsequently underwent cranioplasty and/or fronto-orbital advancement and those who did not (subsequent procedures, 2.45 ± 0.55; no subsequent procedures, 1.88 ± 0.78; p = 0.1087). CONCLUSIONS: The Whitaker classification exhibits low interrater reliability and does not predict future treatment. It may benefit craniofacial surgeons to create new evaluation tools with greater precision, to improve the quality of patient care and craniofacial outcomes research.

Contraception for the perimenopausal woman.

Perimenopause, or the menopause transition, is a time in a woman's life that bridges her reproductive years through to the non-surgical cessation of ovulation, or menopause. For many women this time is one of changes: changes in gynecological issues, onset of symptoms not experienced in her youth and increasing risks for adverse medical conditions. Despite the clear changes that occur for many women during this time, one critical issue is frequently ignored, namely, that, until the onset of menopause, she is exposed to pregnancy if sexually active, and pregnancy for older reproductive women is fraught with considerable increases in morbidity and mortality compared to younger women. This paper will present a review of the reproductive issues of the perimenopause and interventions geared to preventing pregnancy and relieving menopause-related symptoms. As counseling remains a critical aspect in empowering women to make informed choices about their health care, this paper will present current evidence that will help clinicians provide accurate reproductive counseling to women in the menopause transition.

Assessing the midface in Muenke syndrome: A cephalometric analysis and review of the literature.

BACKGROUND: Max Muenke included midface hypoplasia as part of the clinical syndrome caused by the Pro250Arg FGFR3 mutation that now bears his name. Murine models have demonstrated midface hypoplasia in homozygous recessive mice only, with heterozygotes having normal midfaces; as the majority of humans with the syndrome are heterozygotes, we investigated the incidence of midface hypoplasia in our institution's clinical cohort. METHODS: We retrospectively reviewed all patients with a genetic and clinical diagnosis of Muenke syndrome from 1990 to 2014. Review of clinical records and photographs included skeletal Angle Class, dental occlusion, and incidence of orthognathic intervention. Cephalometric evaluation of our patients was compared to the Eastman Standard Values. RESULTS: 18 patients met inclusion criteria - 7 females and 11 males, with average follow-up of 11.2 years (1.0-23.1). Cephalometric analysis revealed an average sella-nasion-A point angle (SNA) of 82.5 (67.8-88.8) and an average sella-nasion-B point angle (SNB) of 77.9 (59.6-84.1). The SNA of our cohort was found to be significantly different from the Eastman Standards (p = 0.017); subgroup analysis revealed that this was due to the mixed dentition group which had a higher than average SNA. 12 patients were noted to be in Class I occlusion, 4 in Class II malocclusion, and 2 in Class III malocclusion. Only one patient (6%) underwent orthognathic surgery for Class III malocclusion. CONCLUSIONS: While a part of the original description of Muenke syndrome, clinically significant midface hypoplasia is not a common feature. This data is important, as it allows more accurate counseling of patients and families. LEVEL OF EVIDENCE: III.

The prevalence of strabismus in unilateral coronal synostosis.

BACKGROUND: While there is a clear correlation between unilateral coronal synostosis (UCS) and ocular motility abnormalities, the literature provides little information as to the true epidemiology of strabismus, or the underlying etiology of these paralleled pathologies. The purpose of this study is to investigate the rate of oculomotor abnormalities associated with UCS and its management. METHODS: A retrospective review of all patients identified to have single-suture, nonsyndromic UCS treated by fronto-orbital advancement at a tertiary craniofacial referral center from 1977 to 2013 was performed. Inclusion criteria mandated complete medical, surgical, and ophthalmological records. Patients were evaluated for strabismus both preoperatively and postoperatively, and as to whether eye muscle surgery was performed. RESULTS: A total of 181 patients underwent treatment for UCS at our institution during the study period, of which 79 met the inclusion criteria. Twenty-nine patients had strabismus prior to any craniofacial surgical intervention. Following fronto-orbital advancement, 23 patients (46 %) developed a new onset strabismus. Fifty-five patients had no change in their preoperative ocular examination, and one patient had resolution of preoperative strabismus. Of the 51 patients who had postoperative strabismus, 30 went on to have eye muscle surgery. There were no statistically significant differences in gender (p=0.477), race (p=0.395), sidedness of suture involvement (p=0.552), or age at intervention (p=0.66) in comparing the group with new postoperative strabismus and those without. CONCLUSIONS: This study sheds new light on the prevalence of strabismus in UCS, and more importantly, the risk of developing strabismus in the setting of conventional fronto-orbital advancement. This data will allow more accurate preoperative counseling and reinforces the important role of ophthalmologists as members of the multidisciplinary craniofacial team.

Perioperative complications associated with intracranial procedures in patients with nonsyndromic single-suture craniosynostosis.

Within the diagnosis "craniosynostosis," there is a subset of patients who present with isolated, nonsyndromic, single-suture involvement. This study evaluates perioperative complications in this specific subset of patients over 4 decades at a single institution. To do so, we performed a retrospective review on consecutive patients undergoing correction of single-suture synostosis from May 1977 to January 2013 at a tertiary pediatric craniofacial center. Demographic information, operative details, and perioperative course were collected. Complications were categorized as either major or minor. A χ(2) test and Fisher exact test were used to compare all categorical variables. Continuous variables were analyzed using Wilcoxon rank-sum and Kruskal-Wallis tests.Seven hundred forty-six patients underwent surgical correction of nonsyndromic craniosynostosis. Of these, there were 307 (41.2%) sagittal, 201 (26.9%) metopic, and 238 (31.9%) unicoronal. Thirty-four patients had complications (4.6%). Eight were considered major (1.1%), including one postoperative mortality in a patient with hypoplastic left-sided heart syndrome. Minor complications occurred in 26 patients (3.5%) and included subgaleal hematoma (n = 3), seroma (n = 4), and superficial wound infection (n = 5). Metopic and sagittal suture involvement was significantly associated with a higher complication rate (P = 0.04). A child with isolated single suture synostosis and any comorbidity had a significantly greater risk of any complication (P < 0.001; odds ratio, 3.8) and specifically an increased risk of major complication (P = 0.031; odds ratio, 6.0). Subclassification of patients by time period yielded no statistically significant changes in perioperative morbidity. To conclude, these data allow us to counsel families more accurately with regard to morbidity and mortality and may potentially serve as a benchmark for future quality improvement work.

A critical evaluation of long-term aesthetic outcomes of fronto-orbital advancement and cranial vault remodeling in nonsyndromic unicoronal craniosynostosis.

BACKGROUND: This study reports long-term aesthetic outcomes with fronto-orbital advancement and cranial vault remodeling in treating unicoronal synostosis over a 35-year period. METHODS: Retrospective review was performed on patients with isolated unicoronal synostosis from 1977 to 2012. Demographic, preoperative phenotypic, and long-term aesthetic outcomes data were analyzed with chi-squared and Fisher's exact test for categorical data and Wilcoxon rank-sum and Kruskal-Wallis rank for continuous data. RESULTS: A total of 238 patients were treated; 207 met inclusion criteria. None underwent secondary intervention for intracranial pressure. At definitive intervention, there 96 (55 percent) Whitaker class I patients, 11 (6 percent) class II, 62 (35 percent) class III, and six (3 percent) class IV. Nasal root deviation and occipital bossing each conferred an increased risk of Whitaker class III/IV [OR, 4.4 (1.4 to 13.9), p = 0.011; OR, 2.6 (1.0 to 6.8), p = 0.049]. Patients who underwent bilateral cranial vault remodeling with extended unilateral bandeau were less likely Whitaker class III/IV at latest follow-up compared with those undergoing strictly unilateral procedures [OR, 0.2 (0.1 to 0.7), p = 0.011]. Overcorrection resulted in decreased risk of temporal hollowing [OR, 0.3 (0.1 to 1.0), p = 0.05]. Patients with 5 years or more of follow-up were more likely to develop supraorbital retrusion [OR, 7.2 (2.2 to 23.4), p = 0.001] and temporal hollowing [OR, 3.7 (1.5 to 9.6), p = 0.006] and have Whitaker class III/IV outcomes [OR, 4.9 (1.8 to 12.8), p = 0.001]. CONCLUSION: Traditional fronto-orbital advancement and cranial vault remodeling appears to mitigate risk of intracranial pressure but may lead to aesthetic shortcomings as patients mature, namely fronto-orbital retrusion and temporal hollowing. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Factors associated with survival in a large series of patients with malignant pleural mesothelioma in New South Wales.

BACKGROUND: Although the prognosis of most patients presenting with malignant pleural mesothelioma (MPM) is poor, a small proportion survives long term. We investigated factors associated with survival in a large patient series. METHODS: All patients registered with the NSW Dust Diseases Board (2002-2009) were included in an analysis of prognostic factors using Kaplan-Meier and Cox regression analysis. On the basis of these analyses, we developed a risk score (Prognostic Index (PI)). RESULTS: We identified 910 patients: 90% male; histology (epithelioid 60%; biphasic 13%; sarcomatoid 17%); stage (Tx-I-II 48%; III-IV 52%); and calretinin expression (91%). TREATMENT: chemotherapy(CT) 44%, and extrapleural-pneumonectomy (EPP) 6%. Median overall survival (OS) was 10.0 months. Longer OS was associated with: age <70 (13.5 vs 8.5 months; P<0.001); female gender (12.0 vs 9.9 months; P<0.001); epithelioid subtype (13.3 vs 6.2 months; P<0.001); ECOG status 0 (27.4 vs 9.7 months; P=0.015), calretinin expression (10.9 vs 5.5 months; P<0.001); neutrophil-lymphocyte ratio (NLR) <5 (11.9 vs 7.5 months; P<0.001); platelet count <400 (11.5 vs 7.2 months; P<0.001); and normal haemoglobin (16.4 vs 8.8 months; P<0.001). On time-dependent analysis, patients receiving pemetrexed-based chemotherapy (HR=0.83; P=0.048) or EPP (HR=0.41; P<0.001) had improved survival. Age, gender, histology, calretinin and haematological factors remained significant on multivariate analysis. In all, 24% of patients survived >20 months: 16% of these receiving EPP, and 66% CT. The PI offered improved prognostic discrimination over one of the existing prognostic models (EORTC). CONCLUSIONS: We identified calretinin expression, age, gender, histological subtype, platelet count and haemoglobin level as independent prognostic factors. Patients undergoing EPP or pemetrexed-based chemotherapy demonstrated better survival, but 84% and 34% of long survivors, respectively, did not receive radical surgery or chemotherapy.

An evaluation of complications, revisions, and long-term aesthetic outcomes in nonsyndromic metopic craniosynostosis.

BACKGROUND: The authors evaluated the complications, revisions, and long-term aesthetic outcomes of patients with isolated metopic synostosis. METHODS: A retrospective chart review was performed on consecutive metopic craniosynostosis patients treated from June of 1987 to June of 2012 at The Children's Hospital of Philadelphia. Patient demographics, operative details, and postoperative data were collected. Outcomes were reported as Whitaker classification and postoperative clinical characteristics assessed before additional interventions. Reoperation in patients with greater than 5 years of follow-up was noted. Appropriate statistical analyses were applied. RESULTS: From 1987 to 2012, 178 patients underwent surgical correction of isolated metopic craniosynostosis, and 147 met inclusion criteria. Average age at surgery was 0.83 year (range, 0.3 to 4.7 years); average follow-up was 5.8 years (range, 1.0 to 17.8 years). There were 13 surgical complications (8.8 percent), three major (2.0 percent), and 10 minor (6.8 percent). At follow-up, 67 patients (56.8 percent) were classified as Whitaker class I, six (5.1 percent) as class II, 43 (36.4 percent) as class III, and two (1.7 percent) as class IV. Patients with greater than 5 years' follow-up (n = 57) were more likely to have temporal hollowing (OR, 2.9; 95 percent CI, 1.2 to 7.3; p = 0.021), lateral orbital retrusion (OR, 4.9; 95 percent CI, 1.9 to 12.7; p = 0.001), and Whitaker class III or IV classification (OR, 4.0; 95 percent CI, 1.5 to 10.6; p = 0.006) compared with those with less than 5 years' follow-up. CONCLUSION: This study reports low complication and reoperation rates in the treatment of isolated metopic craniosynostosis, but demonstrates a clear trend toward worsening aesthetic outcomes over time. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed. METHODS: Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients. RESULTS: Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis. CONCLUSION: These results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.

The impact of a parent liaison at a major craniofacial center.

The psychosocial impact of craniofacial disfigurement affects both the developing child and his/her family. The Facial Reconstruction Center at the Children's Hospital of Philadelphia has employed a Parent Liaison (PL) to provide psychosocial support to families and has been an invaluable resource in this regard. We hypothesize that a PL impacts the overall outcome of the surgery by building trust between the parents and medical institution, and increasing satisfaction. An anonymous satisfaction survey was sent to families of craniofacial patients treated between January 1976 and June 2012. All patients who had undergone at least 1 craniofacial procedure had addresses on file and were included in this study. Statistical analyses were performed using the Mann-Whitney U test.During the study, 441 surveys were mailed to families meeting the inclusion criteria. A total of 151 families returned completed surveys (34.2%), and 121 surveys were included for analysis (27.4%). In rating overall satisfaction, families who met with the PL had statistically higher scores than those who had not (P = 0.0011). Parents who met with the PL preoperatively reported greater satisfaction in time spent answering questions (P = 0.0029) and the perception that questions were adequately answered (P = 0.0039). No statistical difference was observed in postoperative preparedness between families that did and did not meet the PL. The results demonstrate that the PL is beneficial in the education, experience, and satisfaction of families treated at a large Craniofacial Center. The PL complements the surgeon's treatment of the physical by adding psychosocial support.

Nonadherence to the isochrony principle in forged signatures.

Highly programmed skilled movements are executed in such a way that their kinematic features adhere to certain rules referred to as minimization principles. One such principle is the isochrony principle, which states that the duration of voluntary movement remains approximately constant across a range of movement distances; that is, movement duration is independent of movement extent. The concept of isochrony suggests that some information stored in the motor program is constant, thus reducing the storage demands of the program. The aim of the present study was to examine whether forged signatures can be distinguished from genuine signatures on the basis of isochrony kinematics. Sixty writers were asked to write their own signatures and to forge model signatures representing three different writing styles: text-based, stylized, and mixed. All signatures were digitized to enable high precision dynamic analyses of stroke kinematics. Vertical stroke duration and absolute amplitude were measured for each pen stroke of the signatures using MovAlyzeR(®) software. Slope coefficients derived from simple regression models of the relationship between stroke duration and amplitude served as our measure of isochrony. The slope coefficient reflects the degree to which stroke duration increases in relation to stroke amplitude. Higher coefficients indicate greater increases in stroke duration for a given stroke amplitude and thus violate the isochrony principle. We hypothesized that the duration-amplitude coefficients for forged signatures would be significantly greater than for genuine signatures suggesting non-adherence to the isochrony principle. Results indicated that regardless of the style of the writer, genuine signatures were associated with low slope coefficients Pen strokes forming forged signatures had significantly greater duration-amplitude slope coefficients than genuine signatures. These findings suggest that when forging signatures, writers execute pen movements having steeper duration-amplitude relationships than for genuine signatures.

Soft-tissue refinements in the treatment of unicoronal craniosynostosis: the rotational forehead flap.

Unicoronal craniosynostosis is characterized by ipsilateral superior and posterior displacement of the supraorbital rim and frontal bone, ipsilateral widening of the palpebral fissure, ipsilateral superior displacement of the brow, and contralateral brow depression. In the literature, surgical treatment has focused on bony anatomy, with little written about soft-tissue correction. Over the last 25 years, the senior author (L.A.W.) has incorporated soft-tissue refinements, including a rotational flap of the forehead, elevating the contralateral brow, depressing the ipsilateral brow, and equilibrating the supratarsal sulci in unicoronal craniosynostosis. This rotational forehead repositioning is a simple innovation that has provided for improved orbital and brow symmetry on long-term follow-up.

A retrospective analysis of extended-interval dosing and the impact on bisphosphonate compliance in the US Military Health System.

UNLABELLED: This study evaluated whether patients treated with bisphosphonates in the US Military Health System were more compliant with treatment given monthly versus weekly. While medication compliance did improve with treatment given monthly, overall compliance with bisphosphonates was still suboptimal suggesting the need for further strategies to improve compliance with treatment for osteoporosis. INTRODUCTION: The study objective was to evaluate the relationship between bisphosphonate dosing interval and medication compliance among new users initiating oral bisphosphonates. METHODS: We conducted a retrospective observational cohort study of administrative claims data in the US Military Health System to examine medication compliance among 22,363 new users of oral bisphosphonates starting weekly (68%) or monthly (32%) therapy. Medication compliance during the first year of treatment was measured using two methods: (1) medication possession ratio (MPR) with compliance defined as ≥80% of days covered and (2) time to first gap of more than 30 days following initiation. Logistic regression and a proportional hazards model were used to detect differences in medication compliance between cohorts. RESULTS: After the first year of therapy, 57% of subjects were not compliant with bisphosphonates (MPR <80%), while 84% experienced a gap in treatment of more than 30 days. After adjustment for study covariates, the odds of a patient being compliant with treatment was 21% higher among monthly users compared to weekly users (OR 1.207, 95% confidence interval (CI) 1.119-1.257). Similarly, the risk of experiencing a 30-day gap in treatment was 6% lower among monthly users compared to weekly users (HR 0.934, 95% CI 0.905-0.964). CONCLUSIONS: Patients receiving oral bisphosphonates on a monthly basis showed higher rates of medication compliance compared to weekly dosing in our study. However, compliance with bisphosphonates among all new users was suboptimal, suggesting the need for improved strategies to enhance compliance with oral bisphosphonates in the US Military Health System.