In vitro accuracy evaluation of image-guided robot system for direct cochlear access

HYPOTHESIS A previously developed image-guided robot system can safely drill a tunnel from the lateral mastoid surface, through the facial recess, to the middle ear, as a viable alternative to conventional mastoidectomy for cochlear electrode insertion. BACKGROUND Direct cochlear access (DCA) provides a minimally invasive tunnel from the lateral surface of the mastoid through the facial recess to the middle ear for cochlear electrode insertion. A safe and effective tunnel drilled through the narrow facial recess requires a highly accurate image-guided surgical system. Previous attempts have relied on patient-specific templates and robotic systems to guide drilling tools. In this study, we report on improvements made to an image-guided surgical robot system developed specifically for this purpose and the resulting accuracy achieved in vitro. MATERIALS AND METHODS The proposed image-guided robotic DCA procedure was carried out bilaterally on 4 whole head cadaver specimens. Specimens were implanted with titanium fiducial markers and imaged with cone-beam CT. A preoperative plan was created using a custom software package wherein relevant anatomical structures of the facial recess were segmented, and a drill trajectory targeting the round window was defined. Patient-to-image registration was performed with the custom robot system to reference the preoperative plan, and the DCA tunnel was drilled in 3 stages with progressively longer drill bits. The position of the drilled tunnel was defined as a line fitted to a point cloud of the segmented tunnel using principle component analysis (PCA function in MatLab). The accuracy of the DCA was then assessed by coregistering preoperative and postoperative image data and measuring the deviation of the drilled tunnel from the plan. The final step of electrode insertion was also performed through the DCA tunnel after manual removal of the promontory through the external auditory canal. RESULTS Drilling error was defined as the lateral deviation of the tool in the plane perpendicular to the drill axis (excluding depth error). Errors of 0.08 ± 0.05 mm and 0.15 ± 0.08 mm were measured on the lateral mastoid surface and at the target on the round window, respectively (n =8). Full electrode insertion was possible for 7 cases. In 1 case, the electrode was partially inserted with 1 contact pair external to the cochlea. CONCLUSION The purpose-built robot system was able to perform a safe and reliable DCA for cochlear implantation. The workflow implemented in this study mimics the envisioned clinical procedure showing the feasibility of future clinical implementation.

Future prospects for SPECT imaging using the radiolanthanide terbium-155 — production and preclinical evaluation in tumor-bearing mice

We assessed the suitability of the radiolanthanide 155 Tb (t1/2 = 5.32 days, Eγ = 87 keV (32%), 105 keV (25%)) in combination with variable tumor targeted biomolecules using preclinical SPECT imaging. Methods 155Tb was produced at ISOLDE (CERN, Geneva, Switzerland) by high-energy (~ 1.4 GeV) proton irradiation of a tantalum target followed by ionization and on-line mass separation. 155 Tb was separated from isobar and pseudo-isobar impurities by cation exchange chromatography. Four tumor targeting molecules – a somatostatin analog (DOTATATE), a minigastrin analog (MD), a folate derivative (cm09) and an anti-L1-CAM antibody (chCE7) – were radiolabeled with 155 Tb. Imaging studies were performed in nude mice bearing AR42J, cholecystokinin-2 receptor expressing A431, KB, IGROV-1 and SKOV-3ip tumor xenografts using a dedicated small-animal SPECT/CT scanner. Results The total yield of the two-step separation process of 155 Tb was 86%. 155 Tb was obtained in a physiological l-lactate solution suitable for direct labeling processes. The 155 Tb-labeled tumor targeted biomolecules were obtained at a reasonable specific activity and high purity (> 95%). 155 Tb gave high quality, high resolution tomographic images. SPECT/CT experiments allowed excellent visualization of AR42J and CCK-2 receptor-expressing A431 tumors xenografts in mice after injection of 155 Tb-DOTATATE and 155 Tb-MD, respectively. The relatively long physical half-life of 155 Tb matched in particular the biological half-lives of 155 Tb-cm09 and 155 Tb-DTPA-chCE7 allowing SPECT imaging of KB tumors, IGROV-1 and SKOV-3ip tumors even several days after administration. Conclusions The radiolanthanide 155 Tb may be of particular interest for low-dose SPECT prior to therapy with a therapeutic match such as the β--emitting radiolanthanides 177Lu, 161 Tb, 166Ho, and the pseudo-radiolanthanide 90Y.

The importance of pneumococcal capsule in inate immunity and biofilm formation

Chapter 1 gives an overview about Streptococcus pneumoniae, its role as a human pathogen and its virulence factors. Additionally, biofilm development and its relevance in clinics are introduced, and the innate immune response to pneumococcus as well as bacterial-viral interactions in the upper respiratory tract are also discussed. Chapter 2 emphasizes the three main topics of this thesis: the role of capsule and pneumolysin in the immune response in the respiratory tract, biofilm formation of S. pneumoniae serotypes and commensal streptococci in vitro, and host innate immune responses to RSV and S. pneumoniae during in vitro co-infections. Aims and hypotheses are provided here. Chapter 3 is divided into two parts: First, the release of the pro-inflammatory cytokines CXCL8 and IL-6 from the human pharyngeal epithelial cell line Detroit 562 and from human bronchial epithelial cells (iHBEC) is described in response to S. pneumoniae. Capsule was shown to suppress the release of both cytokines in both cell lines tested, but release was much less from iHBEC cells. During intranasal colonization of mice, suppression of CXCL8 release by the capsule was also observed in vivo, but the effect was only measured in the absence of pneumolysin. Long term, stable nasopharyngeal carriage in a mouse model resulted in the dissemination of nonencapsulated pneumococci into the lungs, whereas encapsulated strains remained in the nasopharynx. The S. pneumoniae capsule thus plays a role in modulation of the pro-inflammatory immune response in the respiratory tract. Second, results on immunological cells and immune regulation in a long term, stable nasopharyngeal carriage mouse model are presented. Mice were infected with encapsulated or nonencapsulated pneumococcal strains, and after 1, 3, 8 and 15 days, were sacrificed to evaluate the numbers of CD45+ cells, neutrophils, macrophages, FoxP3+ regulatory T-cells and CD3+ T-cells in the nasal mucosa as well as the amount of secreted IL-10 in the nasopharynx. Nasopharyngeal colonization which is effectively silent resulted in the stimulation of FoxP3+ regulatory T-cells and IL-10 release associated with immune homeostasis, whereas lung infiltration was required to increase the number of neutrophils and macrophages resulting in a stronger innate immune response in the nasal mucosa. Chapter 4 contains results of mono- and co-stimulation using RSV and pneumococci or pneumococcal virulence factors on the human bronchial epithelial cell line BEAS-2B. An increase in CXCL8 and IL-6 levels was measured for mixed stimulations of RSV and pneumococcus when encapsulated bacteria were used. Increasing pneumolysin concentrations resulted in enhanced CXCL8 levels. Priming of bronchial epithelial cells with RSV opens the door for more severe pneumococcal infections. Chapter 5 is composed of two parts: The first part describes initial biofilm formation of serotypes 6B and 7F in a static model in vitro. Biofilms of both serotypes contained SCVs, but only serotype 6B increased in SCV formation between 16 and 65h of incubation. SCV stability was tested by passaging clones in complex medium, where SCV production is not associated with advantages in growth. Serotype 6B lost the SCV phenotype indicating a fast adaptation to a changing nutritional environment. Limitations of our in vitro model are discussed. The second part is about initial biofilm formation of mixed culture growth of S. pneumoniae with commensal streptococci. Competition dominates this process. S. oralis and pneumococcus compete for nutrients, whereas mixed species growth of S. mitis or S. pseudopneumoniae with S. pneumoniae is mainly influenced by other factors. In Chapter 6 the findings of chapters 3, 4 and 5 are discussed and an outlook for further studies is provided. Chapters 7, 8, 9, 10 and 11 contain the references, the acknowledgements, the curriculum vitae, the appendix and the declaration of originality.

Evaluation of coughing and nasal discharge as early indicators for an increased risk to develop equine recurrent airway obstruction (RAO).

BACKGROUND It is often assumed that horses with mild respiratory clinical signs, such as mucous nasal discharge and occasional coughing, have an increased risk of developing recurrent airway obstruction (RAO). HYPOTHESIS Compared to horses without any clinical signs of respiratory disease, those with occasional coughing, mucous nasal discharge, or both have an increased risk of developing signs of RAO (frequent coughing, increased breathing effort, exercise intolerance, or a combination of these) as characterized by the Horse Owner Assessed Respiratory Signs Index (HOARSI 1-4). ANIMALS Two half-sibling families descending from 2 RAO-affected stallions (n = 65 and n = 47) and an independent replication population of unrelated horses (n = 88). METHODS In a retrospective cohort study, standardized information on occurrence and frequency of coughing, mucous nasal discharge, poor performance, and abnormal breathing effort-and these factors combined in the HOARSI-as well as management factors were collected at intervals of 1.3-5 years. RESULTS Compared to horses without clinical signs of respiratory disease (half-siblings 7%; unrelated horses 3%), those with mild respiratory signs developed clinical signs of RAO more frequently: half-siblings with mucous nasal discharge 35% (P < .001, OR: 7.0, sensitivity: 62%, specificity: 81%), with mucous nasal discharge and occasional coughing 43% (P < .001, OR: 9.9, sensitivity: 55%, specificity: 89%); unrelated horses with occasional coughing: 25% (P = .006, OR = 9.7, sensitivity: 75%, specificity: 76%). CONCLUSIONS AND CLINICAL IMPORTANCE Occasional coughing and mucous nasal discharge might represent an increased risk of developing RAO.

Assessment of low-flow, low-gradient, severe aortic stenosis: an invasive evaluation is required for decision making.

Low-flow, low-gradient severe aortic stenosis (AS) is characterised by a small aortic valve area (AVA) and low mean gradient (MG) secondary to a low cardiac output and may occur in patients with either a preserved or reduced left ventricular ejection fraction (LVEF). Symptomatic patients presenting with low-flow, low-gradient severe AS have a dismal prognosis independent of baseline LVEF if managed conservatively and should therefore undergo aortic valve replacement if feasible. Transthoracic echocardiography (TTE) is the first-line investigation for the assessment of AS haemodynamic severity. However, when confronted with guideline-discordant AVA (small) and MG (low) values, there are several reasons other than severe AS combined with a low cardiac output which may lead to such a situation, including erroneous measurements, small body size, inherent inconsistencies in the guidelines' criteria, prolonged ejection time and aortic pseudostenosis. The distinction between these various entities poses a diagnostic challenge. However, it is important to make a distinction because each has very different implications in terms of risk stratification and therapeutic management. In such instances, cardiac catheterisation forms an integral part of the work-up of these patients in order to confirm or refute the echocardiographic findings to guide management decisions appropriately.

Generation of a murine hepatic angiosarcoma cell line and reproducible mouse tumor model

Hepatic angiosarcoma (AS) is a rare and highly aggressive tumor of endothelial origin with dismal prognosis. Studies of the molecular biology of AS and treatment options are limited as animal models are rare. We have previously shown that inducible knockout of Notch1 in mice leads to spontaneous formation of hepatic AS. The aims of this study were to: (1) establish and characterize a cell line derived from this murine AS, (2) identify molecular pathways involved in the pathogenesis and potential therapeutic targets, and (3) generate a tumor transplantation model. AS cells retained specific endothelial properties such as tube formation activity, as well as expression of CD31 and Von Willebrand factor. However, electron microscopy analysis revealed signs of dedifferentiation with loss of fenestrae and loss of contact inhibition. Microarray and pathway analysis showed substantial changes in gene expression and revealed activation of the Myc pathway. Exposing the AS cells to sorafenib reduced migration, filopodia dynamics, and cell proliferation but did not induce apoptosis. In addition, sorafenib suppressed ERK phosphorylation and expression of cyclin D2. Injection of AS cells into NOD/SCID mice resulted in formation of undifferentiated tumors, confirming the tumorigenic potential of these cells. In summary, we established and characterized a murine model of spontaneous AS formation and hepatic AS cell lines as a useful in vitro tool. Our data demonstrate antitumor activity of sorafenib in AS cells with potent inhibition of migration, filopodia formation, and cell proliferation, supporting further evaluation of sorafenib as a novel treatment strategy. In addition, AS cell transplantation provides a subcutaneous tumor model useful for in vivo preclinical drug testing.Laboratory Investigation advance online publication, 24 November 2014; doi:10.1038/labinvest.2014.141.

The Glucose-Dependent Insulinotropic Polypeptide Receptor: A Novel Target for Neuroendocrine Tumor Imaging-First Preclinical Studies

A new family of peptide receptors, the incretin receptor family, overexpressed on many neuroendocrine tumors (NETs) is of great importance because it may enable the in vivo peptide-based receptor targeting of a category of NETs that does not express the somatostatin receptor. Impressive in vivo diagnostic data were published for glucagonlike peptide 1 receptor-targeting radiopeptides. Recently, promising in vitro data have appeared for the second member of the incretin family, the glucose-dependent insulinotropic polypeptide (GIP) receptor. This prompted us to develop and evaluate a new class of radioligands with the potential to be used for the in vivo targeting of GIP receptor-positive tumors. METHODS GIP(1-42) was modified C-terminally, and the truncated peptides [Lys(30)(aminohexanoic acid [Ahx]-DOTA)]GIP(1-30)NH2 (EG1), [Lys(16)(Ahx-DOTA)]GIP(1-30)NH2 (EG2), and [Nle(14), Lys(30)(Ahx-DOTA)]GIP(1-30)NH2 (EG4) were conjugated with Ahx-DOTA via the Lys(16) and Lys(30) side chains. Their inhibitory concentration of 50% (IC50) was determined using [(125)I-Tyr(10)]GIP(1-30) as radioligand and GIP(1-30) as control peptide. The DOTA conjugates were labeled with (111)In and (68)Ga. In vitro evaluation included saturation and internalization studies using the pancreatic endocrine cell line INR1G9 transfected with the human GIP receptor (INR1G9-hGIPr). The in vivo evaluation consisted of biodistribution and PET imaging studies on nude mice bearing INR1G9-hGIPr tumors. RESULTS Binding studies (IC50 and saturation studies) showed high affinity toward GIP receptor for the GIP conjugates. Specific in vitro internalization was found, and almost the entire cell-associated activity was internalized (>90% of the cell-bound activity), supporting the agonist potency of the (111)In-vectors. (111)In-EG4 and (68)Ga-EG4 were shown to specifically target INR1G9-hGIPr xenografts, with tumor uptake of 10.4% ± 2.2% and 17.0% ± 4.4% injected activity/g, 1 h after injection, respectively. Kidneys showed the highest uptake, which could be reduced by approximately 40%-50% with a modified-fluid-gelatin plasma substitute or an inhibitor of the serine protease dipeptidyl peptidase 4. The PET images clearly visualized the tumor. CONCLUSION The evaluation of EG4 as a proof-of-principle radioligand indicated the feasibility of imaging GIP receptor-positive tumors. These results prompt us to continue the development of this family of radioligands for imaging of a broad spectrum of NETs.

Evaluation of three different families of bombesin receptor radioantagonists for targeted imaging and therapy of gastrin releasing peptide receptor (GRP-R) positive tumors.

Two new classes of radiolabeled GRP receptor antagonists are studied and compared with the well-established statine-based receptor antagonist DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (RM2, 1; DOTA:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid; Sta:(3S,4S)-4-amino-3-hydroxy-6-methylheptanoic acid). The bombesin-based pseudopeptide DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leuψ(CHOH-CH2)-(CH2)2-CH3 (RM7, 2), and the methyl ester DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-OCH3 (ARBA05, 3) analogues are labeled with (111)In and evaluated in vitro in PC-3 cell line and in vivo in PC-3 tumor-bearing nude mice. Antagonist potency was assessed by immunofluorescence-based receptor internalization and Ca(2+) mobilization assays. The conjugates showed good binding affinity, the IC50 value of 2 (3.2 ± 1.8 nM) being 2 and 10 times lower than 1 and 3. Compared to (111)In-1, (111)In-2 showed higher uptake in target tissues such as pancreas (1.5 ± 0.5%IA/g and 39.8 ± 9.3%IA/g at 4 h, respectively), whereas the compounds had similar tumor uptake (11.5 ± 2.4%IA/g and 11.8 ± 3.9%IA/g at 4h, respectively). The displacement of the radioligand in vivo was different in different receptor positive organs and depended on the displacing peptide.

Implementation and evaluation of permeability-porosity and tortuosity-porosity relationships linked to mineral dissolution-precipitation

Changes of porosity, permeability, and tortuosity due to physical and geochemical processes are of vital importance for a variety of hydrogeological systems, including passive treatment facilities for contaminated groundwater, engineered barrier systems (EBS), and host rocks for high-level nuclear waste (HLW) repositories. Due to the nonlinear nature and chemical complexity of the problem, in most cases, it is impossible to verify reactive transport codes analytically, and code intercomparisons are the most suitable method to assess code capabilities and model performance. This paper summarizes model intercomparisons for six hypothetical scenarios with generally increasing geochemical or physical complexity using the reactive transport codes CrunchFlow, HP1, MIN3P, PFlotran, and TOUGHREACT. Benchmark problems include the enhancement of porosity and permeability through mineral dissolution, as well as near complete clogging due to localized mineral precipitation, leading to reduction of permeability and tortuosity. Processes considered in the benchmark simulations are advective-dispersive transport in saturated media, kinetically controlled mineral dissolution-precipitation, and aqueous complexation. Porosity changes are induced by mineral dissolution-precipitation reactions, and the Carman-Kozeny relationship is used to describe changes in permeability as a function of porosity. Archie’s law is used to update the tortuosity and the pore diffusion coefficient as a function of porosity. Results demonstrate that, generally, good agreement is reached amongst the computer models despite significant differences in model formulations. Some differences are observed, in particular for the more complex scenarios involving clogging; however, these differences do not affect the interpretation of system behavior and evolution.

Sensitivity of the WRF model to PBL parametrisations and nesting techniques: evaluation of wind storms over complex terrain

Simulating surface wind over complex terrain is a challenge in regional climate modelling. Therefore, this study aims at identifying a set-up of the Weather Research and Forecasting Model (WRF) model that minimises system- atic errors of surface winds in hindcast simulations. Major factors of the model configuration are tested to find a suitable set-up: the horizontal resolution, the planetary boundary layer (PBL) parameterisation scheme and the way the WRF is nested to the driving data set. Hence, a number of sensitivity simulations at a spatial resolution of 2 km are carried out and compared to observations. Given the importance of wind storms, the analysis is based on case studies of 24 historical wind storms that caused great economic damage in Switzerland. Each of these events is downscaled using eight different model set-ups, but sharing the same driving data set. The results show that the lack of representation of the unresolved topography leads to a general overestimation of wind speed in WRF. However, this bias can be substantially reduced by using a PBL scheme that explicitly considers the effects of non-resolved topography, which also improves the spatial structure of wind speed over Switzerland. The wind direction, although generally well reproduced, is not very sensitive to the PBL scheme. Further sensitivity tests include four types of nesting methods: nesting only at the boundaries of the outermost domain, analysis nudging, spectral nudging, and the so-called re-forecast method, where the simulation is frequently restarted. These simulations show that restricting the freedom of the model to develop large-scale disturbances slightly increases the temporal agreement with the observations, at the same time that it further reduces the overestimation of wind speed, especially for maximum wind peaks. The model performance is also evaluated in the outermost domains, where the resolution is coarser. The results demonstrate the important role of horizontal resolution, where the step from 6 to 2 km significantly improves model performance. In summary, the combination of a grid size of 2 km, the non-local PBL scheme modified to explicitly account for non-resolved orography, as well as analysis or spectral nudging, is a superior combination when dynamical downscaling is aimed at reproducing real wind fields.

Evaluation of leaders – does gender still matter?

Purpose: Leadership positions are still stereotyped as male, especially in male-dominated fields such as STEM. Therefore, women in such positions run the risk of being evaluated less favorably than men. Our study investigates how female and male leaders in existing teams (engineering project) are evaluated, and how these evaluations change over time. Design/Methodology: Participants worked in 45 teams to develop specific engineering projects. Evaluations of 45 leaders (33% women) by 258 team members (39% women) were analyzed, that is, leaders’ self-evaluation and their evaluation by team members. Results: Although female and male leaders did not differ in their self-evaluations at the beginning of the project, female leaders evaluated themselves better within time. However, team members evaluated female leaders better than male leaders at the beginning of the project. These gender differences disappeared over the time. Limitations: It should be replicated in a non-student sample. Implications: The results show that female leaders entering a male-dominated field (engineering) are evaluated better by team members than male leaders at the beginning of the team work, in line with the ‘shifting standard model’ (Biernat & Fuegen, 2001). While the initial impression formation of female and male leaders is influenced by category membership, its impact decreases over time as a consequence of individualization (Fiske & Neuberg, 1990); this results in similar evaluations over time. Originality: To our knowledge this is the first study to systematically test perceptions of change in the evaluation over time of female and male leaders in natural setting.

The Importance of Patency in Patients with Critical Limb Ischemia Undergoing Endovascular Revascularization for Infrapopliteal Arterial Disease.

Critical limb ischemia (CLI) represents the most severe form of peripheral arterial disease (PAD) and frequently occurs in medically frail patients. CLI patients frequently exhibit multi-segmental PAD commonly including the tibial arterial segment. Endovascular therapy has been established as first-line revascularization strategy for most CLI patients. Restenosis was reported to occur in up to more than two-thirds of CLI patients undergoing angioplasty of complex tibial arterial obstructions. Nevertheless, favorable clinical outcomes were observed for infrapopliteal angioplasty when compared with bypass surgery, despite higher patency rates for the latter. Based on these observations, infrapopliteal patency was considered to be only of secondary importance upon clinical outcomes in CLI patients. In contrast to these earlier observations, however, recent findings from two randomized clinical trials indicate that infrapopliteal patency does impact on clinical outcomes in CLI patients. The purpose of the present manuscript is to provide a critical reappraisal of the present literature on the clinical importance of tibial arterial patency in CLI patients undergoing endovascular revascularization and to discuss utility and limitations of currently available anti-restenosis technologies.

Dissecting abdominal aortic aneurysm in Angiotensin II-infused mice: the importance of imaging

INTRODUCTION Since the initial publication in 2000, Angiotensin II-infused mice have become one of the most popular models to study abdominal aortic aneurysm in a pre-clinical setting. We recently used phase contrast X-ray based computed tomography to demonstrate that these animals develop an apparent luminal dilatation and an intramural hematoma, both related to mural ruptures in the tunica media in the vicinity of suprarenal side branches. AIMS The aim of this narrative review was to provide an extensive overview of small animal applicable techniques that have provided relevant insight into the pathogenesis and morphology of dissecting AAA in mice, and to relate findings from these techniques to each other and to our recent PCXTM-based results. Combining insights from recent and consolidated publications we aimed to enhance our understanding of dissecting AAA morphology and anatomy. RESULTS AND CONCLUSION We analyzed in vivo and ex vivo images of aortas obtained from macroscopic anatomy, histology, high-frequency ultrasound, contrast-enhanced micro-CT, micro-MRI and PCXTM. We demonstrate how in almost all publications the aorta has been subdivided into a part in which an intact lumen lies adjacent to a remodeled wall/hematoma, and a part in which elastic lamellae are ruptured and the lumen appears to be dilated. We show how the novel paradigm fits within the existing one, and how 3D images can explain and connect previously published 2D structures. We conclude that PCXTM-based findings are in line with previous results, and all evidence points towards the fact that dissecting AAAs in Angiotensin II-infused mice are actually caused by ruptures of the tunica media in the immediate vicinity of small side branches.

Evaluation of a Novel Screw Position in a Type III Distal Phalanx Fracture Model: An Ex Vivo Study

OBJECTIVE: Mechanical evaluation of a novel screw position used for repair in a type III distal phalanx fracture model and assessment of solar canal penetration (SCP). STUDY DESIGN: Experimental study. SAMPLE POPULATION: Disarticulated equine hooves (n = 24) and 24 isolated distal phalanges. METHODS: Hooves/distal phalanges cut in a sagittal plane were repaired with 1 of 2 different cortical screw placements in lag fashion. In group 1 (conventional screw placement), the screw was inserted halfway between the proximal border of the solar canal (SC) and the subchondral bone surface on a line parallel to the dorsal cortex, whereas in group 2, the screw was inserted more palmar/plantar, where a perpendicular line drawn from the group 1 position reached the palmar/plantar cortex. Construct strength was evaluated by 3-point bending to failure. SCP was assessed by CT imaging and macroscopically. RESULTS: Screws were significantly longer in group 2 and in forelimbs. Group 2 isolated distal phalanges had a significantly more rigid fixation compared with the conventional screw position (maximum point at failure 31%, bending stiffness 41% higher). Lumen reduction of the SC was observed in 13/52 specimens (all from group 2), of which 9 were forelimbs. CONCLUSIONS: More distal screw positioning compared with the conventionally recommended screw position for internal fixation of type III distal phalangeal fractures allows placement of a longer screw and renders a more rigid fracture fixation. The novel screw position, however, carries a higher risk of SCP

Long-term evaluation of Class II subdivision treatment with unilateral maxillary first molar extraction

OBJECTIVE To evaluate the long-term effects of asymmetrical maxillary first molar (M1) extraction in Class II subdivision treatment. MATERIALS AND METHODS Records of 20 Class II subdivision whites (7 boys, 13 girls; mean age, 13.0 years; SD, 1.7 years) consecutively treated with the Begg technique and M1 extraction, and 15 untreated asymmetrical Class II adolescents (4 boys, 11 girls; mean age, 12.2 years; SD, 1.3 years) were examined in this study. Cephalometric analysis and PAR assessment were carried out before treatment (T1), after treatment (T2), and on average 2.5 years posttreatment (T3) for the treatment group, and at similar time points and average follow-up of 1.8 years for the controls. RESULTS The adjusted analysis indicated that the maxillary incisors were 2.3 mm more retracted in relation to A-Pog between T1 and T3 (β  =  2.31; 95% CI; 0.76, 3.87), whereas the mandibular incisors were 1.3 mm more protracted (β  =  1.34; 95% CI; 0.09, 2.59), and 5.9° more proclined to the mandibular plane (β  =  5.92; 95% CI; 1.43, 10.41) compared with controls. The lower lip appeared 1.4 mm more protrusive relative to the subnasale-soft tissue-Pog line throughout the observation period in the treated adolescents (β  =  1.43; 95% CI; 0.18, 2.67). There was a significant PAR score reduction over the entire follow-up period in the molar extraction group (β  =  -6.73; 95% CI; -10.7, -2.7). At T2, 65% of the subjects had maxillary midlines perfectly aligned with the face. CONCLUSIONS Unilateral M1 extraction in asymmetrical Class II cases may lead to favorable occlusal outcomes in the long term without harming the midline esthetics and soft tissue profile.