Making Informed Choices On Incorporating Chemoprevention into carE (MiCHOICE, SWOG 1904): Design and methods of a cluster randomized controlled trial.

INTRODUCTION: Women with atypical hyperplasia (AH) or lobular carcinoma in situ (LCIS) have a significantly increased risk of breast cancer, which can be substantially reduced with antiestrogen therapy for chemoprevention. However, antiestrogen therapy for breast cancer risk reduction remains underutilized. Improving knowledge about breast cancer risk and chemoprevention among high-risk patients and their healthcare providers may enhance informed decision-making about this critical breast cancer risk reduction strategy. METHODS/DESIGN: We are conducting a cluster randomized controlled trial to evaluate the effectiveness and implementation of patient and provider decision support tools to improve informed choice about chemoprevention among women with AH or LCIS. We have cluster randomized 26 sites across the U.S. through the SWOG Cancer Research Network. A total of 415 patients and 200 healthcare providers are being recruited. They are assigned to standard educational materials alone or combined with the web-based decision support tools. Patient-reported and clinical outcomes are assessed at baseline, after a follow-up visit at 6 months, and yearly for 5 years. The primary outcome is chemoprevention informed choice after the follow-up visit. Secondary endpoints include other patient-reported outcomes, such as chemoprevention knowledge, decision conflict and regret, and self-reported chemoprevention usage. Barriers and facilitators to implementing decision support into clinic workflow are assessed through patient and provider interviews at baseline and mid-implementation. RESULTS/DISCUSSION: With this hybrid effectiveness/implementation study, we seek to evaluate if a multi-level intervention effectively promotes informed decision-making about chemoprevention and provide valuable insights on how the intervention is implemented in U.S. TRIAL REGISTRATION: NCT04496739.

Lasofoxifene versus fulvestrant for ER+/HER2- metastatic breast cancer with an ESR1 mutation: results from the randomized, phase II ELAINE 1 trial.

BACKGROUND: Acquired estrogen receptor alpha (ER/ESR1) mutations commonly cause endocrine resistance in ER+ metastatic breast cancer (mBC). Lasofoxifene, a novel selective ER modulator, stabilizes an antagonist conformation of wild-type and ESR1-mutated ER-ligand binding domains, and has antitumor activity in ESR1-mutated xenografts. PATIENTS AND METHODS: In this open-label, randomized, phase II, multicenter, ELAINE 1 study (NCT03781063), we randomized women with ESR1-mutated, ER+/human epidermal growth factor receptor 2 negative (HER2-) mBC that had progressed on an aromatase inhibitor (AI) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to oral lasofoxifene 5 mg daily or IM fulvestrant 500 mg (days 1, 15, and 29, and then every 4 weeks) until disease progression/toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were safety/tolerability. RESULTS: A total of 103 patients received lasofoxifene (n = 52) or fulvestrant (n = 51). The most current efficacy analysis showed that lasofoxifene did not significantly prolong median PFS compared with fulvestrant: 24.2 weeks (∼5.6 months) versus 16.2 weeks (∼3.7 months; P = 0.138); hazard ratio 0.699 (95% confidence interval 0.434-1.125). However, PFS and other clinical endpoints numerically favored lasofoxifene: clinical benefit rate (36.5% versus 21.6%; P = 0.117), objective response rate [13.2% (including a complete response in one lasofoxifene-treated patient) versus 2.9%; P = 0.124], and 6-month (53.4% versus 37.9%) and 12-month (30.7% versus 14.1%) PFS rates. Most common treatment-emergent adverse events with lasofoxifene were nausea, fatigue, arthralgia, and hot flushes. One death occurred in the fulvestrant arm. Circulating tumor DNA ESR1 mutant allele fraction (MAF) decreased from baseline to week 8 in 82.9% of evaluable lasofoxifene-treated versus 61.5% of fulvestrant-treated patients. CONCLUSIONS: Lasofoxifene demonstrated encouraging antitumor activity versus fulvestrant and was well tolerated in patients with ESR1-mutated, endocrine-resistant mBC following progression on AI plus CDK4/6i. Consistent with target engagement, lasofoxifene reduced ESR1 MAF, and to a greater extent than fulvestrant. Lasofoxifene may be a promising targeted treatment for patients with ESR1-mutated mBC and warrants further investigation.

Differing sizes of bullet entrance holes in skin of the anterior and posterior trunk.

The aim of the present study was to establish whether the size (diameter and area) of bullet entrance holes in skin varies between distant shots to the anterior and posterior trunk, respectively, when using the same ammunition (in concreto pistol cartridges 9 mm Luger). For that purpose, specimens of porcine skin from the belly region and the back were taken (10 samples each) and shot at from a distance of 1.6 m. The entrance holes were photo-documented under standardised conditions. After image processing for contrast enhancement, the maximum diameter and the area of each skin defect were measured automatically by means of an image analysis system. Both size parameters differed significantly depending on the body region affected. On the back with its comparatively thick dermis, the skin defects were considerably smaller than those on the ventral trunk where the corium is less thick. This difference can be explained by the fact that the elastic properties of skin are strongly determined by the connective tissue which is especially rich in fibres. The study results were consistent with the authors' casework experience and support the assumption that the entrance site of gunshot wounds has a major influence on the size of the bullet hole in skin.

A storage ring experiment to detect a proton electric dipole moment.

A new experiment is described to detect a permanent electric dipole moment of the proton with a sensitivity of 10-29 e ⋅ cm by using polarized "magic" momentum 0.7 GeV/c protons in an all-electric storage ring. Systematic errors relevant to the experiment are discussed and techniques to address them are presented. The measurement is sensitive to new physics beyond the standard model at the scale of 3000 TeV.

Pattern injuries from blows with the muzzle end of a handgun.

Pistols, revolvers and blank guns are not only used to discharge cartridges, but also for hits to the victim. In such cases, the blows preferably affect the head and/or the interposed hands protecting the body. The impact is mostly exerted either by the grip of a pistol or the butt of a revolver. In vigorous thrusts inflicted with the muzzle end of the weapon, the edge of the barrel may produce circular punch lesions with central skin flaps roughly corresponding to the bore. As in other kinds of pistol-whipping, the scalp wounds may be associated with fractures of the skull and even with brain contusions. Using the example of a homicide committed by pistol-whipping, the morphological features of blunt injuries from a handgun's muzzle are presented. The characteristic wound pattern found on the victim's head could be reproduced experimentally by forceful blows to the forehead of a slaughtered pig. In the case presented, the dominant hand of the perpetrator showed friction blisters due to prolonged striking with an unhandy tool in the form of a pistol.

Non-traumatic subdural hematoma secondary to septic brain embolism: A rare cause of unexpected death in a drug addict suffering from undiagnosed bacterial endocarditis.

Acute subdural hematomas are mostly due to blunt traumatization of the head. In rare instances, subdural bleeding occurs without evidence of a previous trauma following spontaneous hemorrhage, e.g. from a ruptured aneurysm or an intracerebral hematoma perforating the brain surface and the arachnoid. The paper presents the morphological, microbiological and toxicological findings in a 38-year-old drug addict who was found by his partner in a dazed state. When brought to a hospital, he underwent trepanation to empty a right-sided subdural hematoma, but he died already 4h after admission. Autopsy revealed previously undiagnosed infective endocarditis of the aortic valve as well as multiple infarctions of brain, spleen and kidneys obviously caused by septic emboli. The subdural hematoma originated from a subcortical brain hemorrhage which had perforated into the subdural space. Microbiological investigation of the polypous vegetations adhering to the aortic valve revealed colonization by Streptococcus mitis and Klebsiella oxytoca. According to the toxicological analysis, no psychotropic substances had contributed to the lethal outcome. The case reported underlines that all deaths of drug addicts should be subjected to complete forensic autopsy, as apart from intoxications also natural and traumatic causes of death have to be taken into consideration.

Fat from contused adipose tissue may cause yellow discoloration of clothes in blunt trauma victims.

In some fatalities from intense blunt trauma, the victims' clothes show strikingly yellow discoloration being in topographic correspondence with lacerated skin and crush damage to the underlying fatty tissue. This phenomenon is especially pronounced in light-colored textiles such as underwear made of cotton and in the absence of concomitant blood-staining. The constellation of findings seems to indicate that the fabric has been soaked with liquid body fat deriving from the contused adipose tissue. To check this hypothesis, textiles suspected to be contaminated with fat were investigated in 6 relevant cases. GC-MS-analysis proved the presence of 11 fatty acids. The fatty acid composition was similar to that of human adipose tissue with a high proportion of oleic acid (18:1). In total, the morphological and chemical findings demonstrated that the yellow discoloration of the victims' clothes was caused by fat from traumatized adipose tissue.

Muzzle imprint mark: a patterned injury which may be constituted of intradermal blood extravasations.

The muzzle imprint mark in contact shots is usually regarded as a patterned pressure abrasion depicting the barrel end as well as adjacent constructional components of the weapon. Due to parching after exposure to air, the affected skin assumes a brown color, especially along the contours of the impacting structures. Apart from this well-known type of epidermal damage, the imprint mark may also be formed by intradermal hemorrhages. In some cases, these intracutaneous bleedings manifest themselves as circular, curved or straight reddish lines mirroring the surface relief of the weapon's muzzle end. To estimate the frequency of skin hematomas in muzzle imprints, 35 consecutive contact shots to the head (temple, forehead, submental and occipital region) were evaluated. In 3 cases, the muzzle imprint mark exclusively consisted of intracutaneous bruises surrounding the bullet entrance hole. In 14 cases, the muzzle imprint was composed of both excoriations and intradermal hematomas.

Precision measurement of charged pion and kaon differential cross sections in e+ e- annihilation at sqrt[s]=10.52 GeV.

Measurements of inclusive differential cross sections for charged pion and kaon production in e+ e- annihilation have been carried out at a center-of-mass energy of sqrt[s]=10.52 GeV. The measurements were performed with the Belle detector at the KEKB e+ e- collider using a data sample containing 113×10(6) e+ e- → qq events, where q={u,d,s,c}. We present charge-integrated differential cross sections dσ(h±)/dz for h±={π±,K±} as a function of the relative hadron energy z=2E(h)/sqrt[s] from 0.2 to 0.98. The combined statistical and systematic uncertainties for π± (K±) are 4% (4%) at z∼0.6 and 15% (24%) at z∼0.9. The cross sections are the first measurements of the z dependence of pion and kaon production for z>0.7 as well as the first precision cross section measurements at a center-of-mass energy far below the Z0 resonance used by the experiments at LEP and SLC.

Experimental simulation of reentry shots using a skin-gelatine composite model.

A bullet that has passed in and out of one body segment may continue its way into another part of the body causing a second entrance ("reentry") wound, which is often said to have an atypical and sometimes confusing appearance. To analyze this problem in a systematical approach, 9-mm Parabellum full metal-jacketed projectiles were fired at skin-gelatine composite models simulating the consecutive passage of a bullet through two parts of a body. When there was a distance between the two segments, the primary exit and the reentry skin wounds did not show any distinctive features differing from usual gunshot injuries. In the case of contact between exit and reentry site, the corresponding skin wounds resembled each other as both had central tissue defects surrounded by abrasion areas. The subsequent investigation of the simulant revealed that skin particles from both the exit and the adjacent reentry site had been displaced in the direction of the shot along the whole bullet track of the second segment. The morphological findings are presented and discussed with respect to the pertinent literature, and possible physical ballistic explanations are suggested.

Search for Lorentz and CPT violation effects in Muon spin precession.

The spin precession frequency of muons stored in the (g-2) storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for a nonzero delta omega a(=omega a mu+ - omega a mu-) and a sidereal variation of omega a mu+/-). No significant effect is found, and the following limits on the standard-model extension parameters are obtained: bZ = -(1.0+/-1.1) x 10(-23) GeV; (m mu dZ0 + HXY)=(1.8+/-6.0) x 10(-23) GeV; and the 95% confidence level limits b perpendicular mu+ <1.4 x 10(-24) GeV and b perpendicular mu- <2.6 x 10(-24) GeV.

Textile fibres along the bullet path--experimental study on a skin-gelatine composite model.

In the past, the presence of textile fibres in the bullet track of gunshot injuries in body regions covered with clothes was used to differentiate between entrance and exit wounds; as with handguns, a displacement of textile fibres was considered possible only in the direction of the shot. In the present study, the transfer of textile fibres from the entrance and exit regions into the bullet path was systematically investigated with the help of a skin-gelatine composite model. For this purpose, the skin of the bullet entrance and exit region was covered with textile fabric (jeans or jersey material), before conducting four test series of ten test shots each firing a 9-mm Parabellum full-jacketed projectile from a distance of 2 m. The length of the bullet track was 25 and 8 cm, respectively. Subsequently, the bullet tracks were microscopically investigated in sections for the presence of textile fibres. In all the investigated bullet tracks, textile fibres both from the entrance and exit regions could be demonstrated. The distribution pattern depended on the length of the bullet path and the extension of the temporary cavitation. The results are discussed in relation to the relevant literature.

Effect of shortening the barrel in contact shots from rifles and shotguns.

In a suicidal gunshot fired to the chest from a carbine, the barrel of which had been shortened to half its original length, an unexpectedly large degree of destruction of the anterior thoracic wall with extensive undermining of the subcutis was found. This phenomenon was investigated for reconstructive purposes by firing test shots from two different long guns (caliber 7.92 x 57 repeating rifle with full-jacketed pointed bullet and caliber 12/70 single-barreled shotgun with shotgun slug) into blocks of soap (38 x 25 x 25 cm). The contact shots were fired before and after shortening the barrels (repeating rifle from 60 to 30 cm and single-barreled shotgun from 72 to 36 cm). The volume of the cavities in the simulant was visualized three-dimensionally with the help of a multislice computed tomography (CT) scanner and calculated sectionally. With the repeating rifle and the single-barreled shotgun, the shots from the sawed-off barrels produced significantly larger cavity diameters in the first section of the bullet track. This effect is attributable to the fact that, with a shortened barrel, the gas pressure at the muzzle is higher, thus, leading to increased expansion in the initial part of the wound track in contact shots.

Gunshot-related displacement of skin particles and bacteria from the exit region back into the bullet path.

In previous studies, it was shown that there is a gunshot-related transport of skin particles and microorganisms from the entrance region into the depth of the bullet path. The present study deals with the question of whether gunshots may also cause a retrograde transport of skin particles and microorganisms from the bullet exit region back into the bullet path. For this purpose, we used a composite model consisting of rectangular gelatin blocks and pig skin. The skin pieces were firmly attached to the gelatin blocks on the side where the bullet was to exit. Prior to the test shots, the outer surface of the pig skin was contaminated with a thin layer of a defined bacterial suspension. After drying the skin, test shots were fired from a distance of 10 m using cartridges calibre .38 spec. with different bullet types. Subsequent analyses showed that in all shots with full penetration of the composite model, the bullet path contained displaced skin particles and microorganisms from the skin surface at the exit site. These could be regularly detected in the distal 6-8 cm of the track, occasionally up to a distance of 18 cm from the exit hole. The distribution of skin particles and microorganisms is presented and the possible mechanism of this retrograde transport is discussed.

Measurement of azimuthal asymmetries in inclusive production of hadron pairs in e(+)e(-) annihilation at Belle.

The Collins effect connects transverse quark spin with a measurable azimuthal dependence in the yield of hadronic fragments around the quark's momentum vector. Using two different reconstruction methods, we find evidence of statistically significant azimuthal asymmetries for charged pion pairs in e(+)e(-) annihilation at a center-of-mass energy of 10.52 GeV, which can be attributed to a transverse polarization of the primordial quarks. The measurement was performed using a sample of 79 x 10(6) hadronic events collected with the Belle detector.

Gunshot-related transport of micro-organisms from the skin of the entrance region into the bullet path.

The skin defect of a gunshot entrance wound is caused by the retrograde and anterograde displacement of skin particles. In the present study, we investigated whether gunshots to bacterially contaminated skin are associated with the transport of micro-organisms into the bullet path. The shots were fired into composite models of pig skin and gelatin blocks. The outer surface of the skin was covered with a thin layer of a defined bacterial suspension [green fluorescent protein-labelled Escherichia coli in the preliminary test and Staphylococcus epidermidis, DSM 1798, in the main test series]. After the bacterially contaminated fluid had dried, test shots were fired from a distance of 5 and 10 m using calibre .38 Special cartridges with different bullet types (round nose, truncated cone, hollow point and flat nose). Subsequent bacteriological analyses showed that all the bullet tracks in the gelatin serving as tissue simulant contained displaced micro-organisms from the skin surface. The results are presented and discussed with reference to the transport of skin particles into the depth of the wound track.

Tissue defect at the gunshot entrance wound: what happens to the skin?

To investigate the question what happens to the tissue lost at the entrance wound, experimental studies were performed on composite models consisting of dyed pig skin and gelatin blocks. For the test shots to the skin-gelatin preparations, cartridges calibre .38 spec. with different bullet types (round nose, hollow point, flat nose, truncated cone) were used. In all shots, a multitude of coloured skin particles were macroscopically discernible along the bullet tracks. In addition, small cell aggregations could be demonstrated microscopically even in those sections of the bullet paths which did not show skin fragments visible to the naked eye. The distribution of the skin particles showed certain peculiarities depending on the type of projectile.

Elucidation of a strange gunshot injury.

A 50-year-old obese man sought medical treatment for bleeding injuries in the abdomen and thigh. According to his statement he felt a dull blow on the front of the trunk while he was feeding swans at a lake. The forensic wound findings and the examination of the clothing suggested that the injuries were caused by a single close-range gunshot with the bullet path running nearly vertically downwards and having a total length of 38 cm. The bullet primarily entered in the right mesogastrium, left the body in the right inguinal region, re-entered and ultimately lodged in the right thigh. After confronting the man with the results of the forensic examination he admitted that he himself had caused the gunshot injury accidentally when cleaning his small-bore revolver.

Three subsequent infanticides covered up as SIDS.

Within a period of 9 years a young woman lost 3 daughters during infancy and each time death was attributed to the sudden infant death syndrome. The children had different fathers and died at the ages of 11 weeks, 7 weeks and 2 weeks, respectively. A fourth daughter survived and lives separated from the mother together with her father and is healthy. At autopsy the last of the three deceased infants did not reveal any pre-existing pathological organ findings, except for acute pulmonary emphysema and extensive intra-alveolar bleeding. As a consequence the strong suspicion of mechanical suffocation arose. Subsequent police investigations produced incriminating clues that the first two children had also been suffocated. On confrontation with the autopsy findings and investigation results, the woman confessed that she herself had killed the first two infants by pressing a cushion on their faces. In the case of the third death the baby had been smothered by the child's father who in agreement with the mother put a plastic film on mouth and nostrils.

Measurement of the negative muon anomalous magnetic moment to 0.7 ppm.

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).