ON A SMALL COLLECTION OF BIRDS FROM THE KARIMATA ISLANDS, WEST BORNEO

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ON A SMALL COLLECTION OF BIRDS FROM THE KARIMOEN DJAWA ISLANDS.

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A NEW RACE. OF CYORNIS FROM THE JAVA SEA

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A glycosylphosphatidylinositol-anchored carbonic anhydrase-related protein of Toxoplasma gondii is important for rhoptry biogenesis and virulence

Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites. The protein localizes throughout the rhoptry bulbs of mature tachyzoites and to the outer membrane of nascent rhoptries in dividing tachyzoites, as demonstrated by immunofluorescence and immunoelectron microscopy using specific antibodies. T. gondii mutant tachyzoites lacking TgCA_RP display a growth and invasion phenotype in vitro and have atypical rhoptry morphology. The mutants also exhibit reduced virulence in a mouse model. Our results show that TgCA_RP plays an important role in the biogenesis of rhoptries

ULTRAZVUČNA PROSUDBA MIGRACIJE PLACENTE PREVIJE U ODNOSU NA MAJČINE DEMOGRAFSKE ČIMBENIKE

Objective. To assess the association between maternal age, parity, history of prior cesarean delivery and placental location in evaluating the persistence and rate of placental migration in low-lying or complete placenta previas followed by serial ultrasound examination. Study design. This is a retrospective study of 92 cases of low-lying/placenta previa diagnosed at 28 weeks of gestation followed serially by transvaginal ultrasound. The patients were stratified into three groups depending on the placenta to internal cervical os distance: (1) an overlap of 0.0 cm and over the cervical os (complete previa), (2) 0.1 to 2.9 cm (marginal placenta previa), (3) 3.0 cm or above (normal placental location). The ¬prevalence of complete and marginal placenta previas, and the mean rate of placental »migration« (mm/week) were ¬obtained at 28 and 36 weeks of gestation, and compared with maternal age, parity, history of prior cesarean delivery and placental location. Results. At the time of delivery, 51 patients had placenta previa: 22 complete and 29 marginal placenta previas. In contrast, 41 patients had sufficient placental ’migration’ to be categorized into the normal placental location group. The prevalence of complete placenta of 3.3% and 6.5% at 28 weeks, and 3.3% and 5.4% at 36 weeks’ gestation, for patients who had parity more than 1, or history or prior cesarean delivery (CD), respectively, was not statistically significant. The rate of placental migration was significantly associated with maternal age (p=0.002), while did not differ when stratified by parity (p=0.672) or prior history of CD (p=0.805), or placental location (p=0.147). Conclusion. Maternal age significantly modifies the rate of placenta previa migration. A history of prior CD, maternal parity and placental location did not affect the rate of placental migration in our sample of patients with complete or marginal placenta previa diagnosed by ¬ultrasound at 28 weeks’ gestation.Cilj rada. Prosuditi povezanost dobi majke, pariteta, prethodnog carskog reza i smještaja posteljice, s perzistiranjem ili migracijom posteljice kod nisko nasjele ili predležeće placente previje, praćene serijskim ultrazvučnim pregledima. Način istraživanja. Retrospektivna studija 92 nisko nasjele posteljice ili placente previje, dijagnosticirane s 28 tjedana i serijski ultrazvučno praćene. Bolesnice su bile podijeljene u tri skupine, ovisno o udaljenosti posteljice od unutrašnjeg ušća cerviksa: 1) preraštanje više od 0,0 mm preko ušća cerviksa (kompletna previja); 2) 0,1 do 2,9 cm (marginalna previja); 3) 3,0 ili više cm od ušća cerviksa (normalni smještaj posteljice). Zastupljenost kompletnih i marginalnih placenta previja i srednja vrijednost »migracije« posteljice (mm/tjedan) su utvrđeni s 28 i 36 tjedana trudnoće te uspoređeni s dobi majke, paritetom, ranijim carskim rezom i smještajem posteljice. Rezultati. Od 92 trudnice s 28 tjedana, u vrijeme poroda 51 trudnica je imala placentu previju: 22 kompletnu i 29 marginalnu, dok je u 41 trudnice posteljica dovoljno »migrirala« da bi bila razvrstana u skupinu s normalnim smještajem. Zastupljenost kompletne previje za trudnice s više od jednog poroda od 3,3% s 28 i 3,3% s 36 tjedana, odnosno s prethodnim carskim rezom od 6,5% s 28 i 5,4% s 36 tjedana, nije statistički signifikantno različita. Stopa »migracije« posteljice je znakovito povezana s dobi trudnice (p=0,002), a nije s paritetom (p=0,672), ranijim carskim rezom (p=0,805) ili ležištem posteljice (p=0,147). Zaključak. Dob trudnice znakovito modificira stupanj migracije placente previje. U našem uzorku kompletnih i marginalnih posteljica otkrivenih ultrazvukom s 28 tjedana, raniji carski rez, paritet majke i ležište posteljice (sprijeda/straga) ne utječu na stupanj migracije posteljice

Diagnostic criteria for cancer cachexia: Reduced food intake and inflammation predict weight loss and survival in an international, multi-cohort analysis

Abstract Background Cancer‐associated weight loss (WL) associates with increased mortality. International consensus suggests that WL is driven by a variable combination of reduced food intake and/or altered metabolism, the latter often represented by the inflammatory biomarker C‐reactive protein (CRP). We aggregated data from Canadian and European research studies to evaluate the associations of reduced food intake and CRP with cancer‐associated WL (primary endpoint) and overall survival (OS, secondary endpoint). Methods The data set included a total of 12,253 patients at risk for cancer‐associated WL. Patient‐reported WL history (% in 6 months) and food intake (normal, moderately, or severely reduced) were measured in all patients; CRP (mg/L) and OS were measured in N = 4960 and N = 9952 patients, respectively. All measures were from a baseline assessment. Clinical variables potentially associated with WL and overall survival (OS) including age, sex, cancer diagnosis, disease stage, and performance status were evaluated using multinomial logistic regression MLR and Cox proportional hazards models, respectively. Results Patients had a mean weight change of −7.3% (±7.1), which was categorized as: ±2.4% (stable weight; 30.4%), 2.5–5.9% (19.7%), 6.0–10.0% (23.2%), 11.0–14.9% (12.0%), ≥15.0% (14.6%). Normal food intake, moderately, and severely reduced food intake occurred in 37.9%, 42.8%, and 19.4%, respectively. In MLR, severe WL (≥15%) (vs. stable weight) was more likely (P  100 mg/L: OR 2.30 (95% CI 1.62–3.26)]. Diagnosis, stage, and performance status, but not age or sex, were significantly associated with WL. Median OS was 9.9 months (95% CI 9.5–10.3), with median follow‐up of 39.7 months (95% CI 38.8–40.6). Moderately and severely reduced food intake and CRP independently predicted OS (P < 0.0001). Conclusions Modelling WL as the dependent variable is an approach that can help to identify clinical features and biomarkers associated with WL. Here, we identify criterion values for food intake impairment and CRP that may improve the diagnosis and classification of cancer‐associated cachexia

Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors

Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (177Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with 177Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11

Phase I Trial of Single-Photon Emission Computed Tomography-Guided Liver-Directed Radiotherapy for Patients With Low Functional Liver Volume

BACKGROUND: Traditional constraints specify that 700 cc of liver should be spared a hepatotoxic dose when delivering liver-directed radiotherapy to reduce the risk of inducing liver failure. We investigated the role of single-photon emission computed tomography (SPECT) to identify and preferentially avoid functional liver during liver-directed radiation treatment planning in patients with preserved liver function but limited functional liver volume after receiving prior hepatotoxic chemotherapy or surgical resection. METHODS: This phase I trial with a 3 + 3 design evaluated the safety of liver-directed radiotherapy using escalating functional liver radiation dose constraints in patients with liver metastases. Dose-limiting toxicities were assessed 6-8 weeks and 6 months after completing radiotherapy. RESULTS: All 12 patients had colorectal liver metastases and received prior hepatotoxic chemotherapy; 8 patients underwent prior liver resection. Median computed tomography anatomical nontumor liver volume was 1584 cc (range = 764-2699 cc). Median SPECT functional liver volume was 1117 cc (range = 570-1928 cc). Median nontarget computed tomography and SPECT liver volumes below the volumetric dose constraint were 997 cc (range = 544-1576 cc) and 684 cc (range = 429-1244 cc), respectively. The prescription dose was 67.5-75 Gy in 15 fractions or 75-100 Gy in 25 fractions. No dose-limiting toxicities were observed during follow-up. One-year in-field control was 57%. One-year overall survival was 73%. CONCLUSION: Liver-directed radiotherapy can be safely delivered to high doses when incorporating functional SPECT into the radiation treatment planning process, which may enable sparing of lower volumes of liver than traditionally accepted in patients with preserved liver function. TRIAL REGISTRATION: NCT02626312