The objectives for this study were to determine 1) if there was a trend in stillbirths for the U.S. Holstein population, 2) if stillbirths are the same trait in primiparous and multiparous cows, and 3) what was the role of dystocia in stillbirths. A sample of 666,341 births from the MidStates Dairy Records Processing Center and the National Association of Animal Breeders was used to examine the influence of sire, herd, year, season, sex of calf, parity of dam, calving ease, and gestation length on the survival of the calf. Parity was scored as an ordered variable (1, 2, 3+). Calving ease was scored on a scale of 1 (no assistance) to 3+ (needed assistance). An increasing trend in stillbirths was found in primiparous and multiparous cows. The percentage of stillborn calves in primiparous cows increased from 9.5 in 1985 to 13.2 in 1996. Stillbirths in multiparous cows increased from 5.0 to 6.6% from 1985 to 1996. Variation about the trend was greater in primiparous cows than in multiparous cows. Dystocia was a major determinant of stillbirth incidence, but the association was stronger in primiparous cows. Sex of calf had different associations with stillbirth incidence in primiparous and multiparous cows. Gestation length and season of birth also had significant associations with stillbirth incidence. Logistic regression models with fixed and random effects were fit to the data to preserve the binary nature of the stillbirth response. The expected probability of stillbirths for an average herd and sire was 10% for primiparous cows and 5% for multiparous cows. Replacement of stillborn calves is a substantial cost to the dairy industry at more than $125.3 million per year. Because of the increasing incidence of stillbirths, these costs have increased by $75.9 million from 1985 to 1996.

Purpose We examined the frequency, tumor characteristics, and prognostic impact of HER2 protein expression and gene amplification in patients with curatively resected esophageal adenocarcinoma (EAC). Experimental Design HER2 expression was analyzed by immunohistochemistry (IHC) in surgical EAC specimens (n=713). Gene amplification was examined by fluorescence in situ hybridization (FISH) in a large subset (n=344). Most tumors were T3–4 (66%) or node-positive (72%); 95% were located in the esophagus or gastroesophageal junction. No patient received neoadjuvant therapy. Cox models were used. Results Overall, 17% of EACs were HER2-positive (ie, IHC3+ or IHC2+ with amplification), with strong agreement between HER2 amplification (HER2/CEP17 ratio ≥2) and expression (κ=.83). HER2-positivity was significantly associated with lower tumor grade, less invasiveness, fewer malignant nodes, and the presence of adjacent Barrett’s esophagus (BE). EACs with BE had higher odds of HER2-positivity compared to EACs without BE, independent of pathologic features (odds ratio 1.8 [95% confidence interval (CI) 1.1–2.8], p=.014). Among all cases, HER2-positivity was significantly associated with disease-specific survival (DSS) in a manner that differed by the presence or absence of BE (p for interaction=.0047). In EACs with BE, HER2-positivity was significantly associated with improved DSS (hazard ratio 0.54 [95% CI 0.35–0.84], p=.0065) and overall survival (p=.0022) independent of pathologic features, but was not prognostic among EACs without BE. Conclusions HER2-positivity was demonstrated in 17% of resected EACs and associated with reduced tumor aggressiveness. EACs with BE had nearly twice the odds of being HER2-positive and, within this subgroup, HER2-positivity was independently associated with improved survival.

Peripheral T-cell lymphomas (PTCLs) represent a group of rare hematological cancers of mature T-cell or natural killer cell origin accounting for 10% to 15% of all lymphomas. 1 Although many patients have poor outcomes, some achieve long-term survival. 2,3 Thus, identifying prognostic biomarkers is important to facilitate riskadapted therapy.Chromosomal rearrangements are critical in the molecular pathogenesis of nearly all types of hematologic neoplasms. 4 The best-characterized rearrangements in PTCLs involve the anaplastic lymphoma kinase (ALK) gene, which result in oncogenic ALK fusion proteins and define a specific World Health Organization (WHO) subtype (ALK-positive anaplastic large cell lymphoma [ALCL], representing 6% to 8% of PTCLs). 2,5,6 ALK also serves as a prognostic marker: patients with ALK-positive ALCLs have better outcomes than those with ALK-negative ALCLs or other nodal PTCLs, including angioimmunoblastic T-cell lymphoma (AITL) and PTCL, not otherwise specified (NOS). 2,7 The molecular pathogenesis of other PTCLs is being elucidated. 8 Recurrent chromosomal rearrangements involving the DUSP22-IRF4 locus on 6p25.3 (DUSP22 rearrangements) and the TP53 homolog TP63 on 3q28 recently were reported in ALK-negative ALCL. 9-12 DUSP22 rearrangements are associated with decreased expression of dual-specificity phosphatase-22, an enzyme that regulates mitogen-activated protein kinase signaling. 10,13,14 A retrospective study found that DUSP22 rearrangements were associated with favorable outcomes in ALK-negative ALCL. 12 TP63 rearrangements encoding p63 fusion proteins were associated with aggressive clinical behavior and poor outcomes. 11,12 In the present study, we evaluated the prognostic impact of DUSP22 and TP63 rearrangements in diagnostic tumor biopsy specimens from a population-based Danish cohort of 138 patients with nodal PTCLs. Formalin-fixed, paraffin-embedded tumors from patients diagnosed with PTCL between 1984 and 2011 were retrieved from the pathology departments at 3 Danish tertiary referral centers (Aarhus, Herlev, and Odense University Hospitals). Specimens were pretreatment biopsy specimens from newly diagnosed PTCL patients aged $16 years for whom pre-and posttreatment clinical information was available. Clinicopathological data were obtained from the population-based database of the Danish National Lymphoma Registry, supplemented by medical records. Cases were reviewed and classified by expert hematopathologists, and re-reviewed to assure concordance with current WHO criteria. 15 The study was approved by The Central Denmark Region Committees on Health Research Ethics (record 1-10-72-392-12), the Danish Data Protection Agency (record 1-16-02-26-11), and the institutional review boards at the participating institutions 21. d'Amore F, Relander T, Lauritzsen GF, et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01.

Cold agglutinin disease (CAD) is a chronic hemolytic disorder caused by anti-red blood cell immunoglobulin M (IgM) autoantibodies most often monoclonal with k light-chain restriction. 1,2 The autoantibody reacts at temperatures lower than the body temperature, causing autoagglutination and complementdependent red blood cell destruction. CAD is a rare disease,

Halide perovskite nanocrystals (NCs) have shown impressive advances, exhibiting optical properties that outpace conventional semiconductor NCs, such as near-unity quantum yields and ultrafast radiative decay rates. Nevertheless, the NCs suffer even more from stability problems at ambient conditions and due to moisture than their bulk counterparts. Herein, we report a strategy of employing polymer micelles as nanoreactors for the synthesis of methylammonium lead trihalide perovskite NCs. Encapsulated by this polymer shell, the NCs display strong stability against water degradation and halide ion migration. Thin films comprising these NCs exhibit a more than 15-fold increase in lifespan in comparison to unprotected NCs in ambient conditions and even survive over 75 days of complete immersion in water. Furthermore, the NCs, which exhibit quantum yields of up to 63% and tunability of the emission wavelength throughout the visible range, show no signs of halide ion exchange. Additionally, heterostructures of MAPI and MAPBr NC layers exhibit efficient Förster resonance energy transfer (FRET), revealing a strategy for optoelectronic integration.

Systemic anaplastic large cell lymphomas (ALCLs) are classified into ALK-positive and ALK-negative types. We recently reported that ALK-negative ALCLs are genetically heterogenous. The largest subset, representing 30% of cases, had rearrangements of the DUSP22 locus. These cases had favorable outcomes similar to ALK-positive ALCL, and superior to other ALK-negative ALCLs. Here, we examined the morphologic features of these cases in more detail. First, we conducted blinded review of hematoxylin and eosin slides of 108 ALCLs from our previous study, scoring cases for the presence of 3 histologic patterns and 5 cell types. Cases then were unblinded and re-reviewed to understand these features further. DUSP22-rearranged ALCLs were more likely than other ALK-negative ALCLs to have so-called doughnut cells (23% vs. 5%; P = 0.039), less likely to have pleomorphic cells (23% vs. 49%; P = 0.042), and nearly always (95%) had areas with sheet-like growth (common pattern). To examine the reproducibility of these findings, we conducted blinded review of hematoxylin and eosin slides of 46 additional ALK-negative ALCLs using a 0 to 3 scoring system to predict likelihood of DUSP22 rearrangement, the results of which correlated strongly with subsequent findings by fluorescence in situ hybridization (P < 0.0001). Although all ALCLs share certain morphologic features, ALCLs with DUSP22 rearrangements show significant differences from other ALK-negative ALCLs, typically showing sheets of hallmark cells with doughnut cells and few large pleomorphic cells. These morphologic findings and our previous outcome data suggest that ALK-positive ALCLs and DUSP22-rearranged ALCLs represent prototypical ALCLs, whereas ALCLs lacking rearrangements of both DUSP22 and ALK require further study.

Stillbirth, defined as a calf that dies just prior to, during, or within 48 h of parturition, represents a reoccurring concern among breeders of dairy cattle in the United States. About 11% of parturitions of primiparous Holstein cows result in the death of a calf; 5.7% in multiparous cows. Genetic evaluations can be reported as perinatal survival to 48 h to emphasize the positive information about the trait. The purpose of this research was to: 1) estimate genetic parameters by restricted maximum likelihood for perinatal survival rates; 2) characterize the genetic evaluation of sires for the perinatal survival of their progeny and maternal grandsires for the perinatal survival of their daughters progeny; and 3) estimate genetic trends from 1984 to 1994. Data (n = 666,339) were from the National Association of Animal Breeders calving ease database. Over 600 new young sires were available each year. The binomial response variable, 1 = alive, 0 = stillborn within 48 h of parturition was analyzed by using a sire-maternal grandsire linear mixed model. The model included fixed effects for sex of calf, dystocia, and season of birth, and gestation length as a covariate; correlated random effects of sire and maternal grandsire; and uncorrelated random effects of herd-years. Parturitions of primiparous and multiparous cows were analyzed separately. In primiparous cows, heritability estimates were 1.1 and 2.2% for sire of the calf and maternal grandsire, respectively. The genetic correlation between sire and maternal grandsire predicted transmitting ability (PTA) for perinatal survival, was 0.31; simple product moment correlations among sire-MGS PTA were 0.43 and 0.46 for primiparous and multiparous cows, respectively. The PTA for sire of the calf ranged from -2.9 (lower survival) to 2.8% (higher survival). Mean PTA from 1984 to 1994 was quite variable from year to year. Evidence showed a slightly negative, but nonsignificant, genetic trend in perinatal survival (-0.04% per year for sires and -0.02% per year for maternal grandsires). Estimates of genetic parameters and genetic trends for data from multiparous cows are also reported. Correlations among PTA for perinatal survival, milk yield, and calving ease are given.

Although changes in environment and management are primarily implicated for the decline in reproductive efficiency of Holstein cows during the past 25 yr, fertility of the male must not be overlooked. Recent measures of scrotal circumference, semen quantity/ quality are comparable to values reported for Holstein sires in 1969. Technological advances in semen processing are reflected in fertilization rates using cryopreserved semen in the late 1990s comparable to those reported for non-frozen semen in the 1950s. The fertility potential of an artificial insemination (AI) dose is a function of the quantity, quality, and health status of the semen contained therein. Management of sire health and associated disease testing protocols are paramount. Semen quality evaluations, adjustments to cell numbers per dose, and culling of ejaculates and/ or bulls, minimize variation in fertility among ejaculates and/or sires released for sale. Identification of additional semen quality attributes associated with fertility may provide more accurate methods to predict, manage, and select for AI sire fertility. Because the values of most known semen quality traits are highly correlated, any new technology must be considered with respect to the additive benefit imparted compared to existing methodologies (improved fertility prediction or economic utility of implementation). Cryopreservation techniques that extend the duration of post-thaw sperm survival and/or reduce rates of capacitation may reduce sensitivity to insemination timing and are promising opportunities to improve fertility from the male perspective. Unfortunately, the association between semen quality and fertility is usually limited by the accuracy of the fertility estimate. Fixed