The Spitzer South Pole Telescope Deep Field Survey: Linking galaxies and halos at z=1.5

We present an analysis of the clustering of high-redshift galaxies in the recently completed 94 deg$^2$ Spitzer-SPT Deep Field survey. Applying flux and color cuts to the mid-infrared photometry efficiently selects galaxies at $z\sim1.5$ in the stellar mass range $10^{10}-10^{11}M_\odot$, making this sample the largest used so far to study such a distant population. We measure the angular correlation function in different flux-limited samples at scales $>6^{\prime \prime}$ (corresponding to physical distances $>0.05$ Mpc) and thereby map the one- and two-halo contributions to the clustering. We fit halo occupation distributions and determine how the central galaxy's stellar mass and satellite occupation depend on the halo mass. We measure a prominent peak in the stellar-to-halo mass ratio at a halo mass of $\log(M_{\rm halo} / M_\odot) = 12.44\pm0.08$, 4.5 times higher than the $z=0$ value. This supports the idea of an evolving mass threshold above which star formation is quenched. We estimate the large-scale bias in the range $b_g=2-4$ and the satellite fraction to be $f_\mathrm{sat}\sim0.2$, showing a clear evolution compared to $z=0$. We also find that, above a given stellar mass limit, the fraction of galaxies that are in similar mass pairs is higher at $z=1.5$ than at $z=0$. In addition, we measure that this fraction mildly increases with the stellar mass limit at $z=1.5$, which is the opposite of the behavior seen at low-redshift.Comment: 32 pages, 22 figures. Published in MNRA

FSD-HSO Optimization Algorithm for Closed Fringes Interferogram Demodulation

Due to the physical nature of the interference phenomenon, extracting the phase of an interferogram is a known sinusoidal modulation problem. In order to solve this problem, a new hybrid mathematical optimization model for phase extraction is established. The combination of frequency guide sequential demodulation and harmony search optimization algorithms is used for demodulating closed fringes patterns in order to find the phase of interferogram applications. The proposed algorithm is tested in four sets of different synthetic interferograms, finding a range of average relative error in phase reconstructions of 0.14–0.39 rad. For reference, experimental results are compared with the genetic algorithm optimization technique, obtaining a reduction in the error up to 0.1448 rad. Finally, the proposed algorithm is compared with a very known demodulation algorithm, using a real interferogram, obtaining a relative error of 1.561 rad. Results are shown in patterns with complex fringes distribution

Acute Postoperative Infectious Endophthalmitis: Advances in Diagnosis and Treatment

Acute postoperative infectious endophthalmitis remains one of the most dreaded complications of ophthalmic surgery. One of the keys to success in treating this complication is to make an early clinical diagnosis and, if possible, an etiologic diagnosis that can guide treatment with antibiotic therapy. Different antibiotic therapy modalities have emerged over the years that have made it possible to treat even resistant strains of various microorganisms that cause endophthalmitis. Another relevant advance made in the etiological diagnosis of endophthalmitis is the advent of molecular biology techniques, such as the real-time polymerase chain reaction, which can detect minimal amounts of the genetic material of the causative microorganism present in the vitreous in a short period of time, thus improving treatment outcomes with better-guided therapy with intravitreal antibiotics. Aside from advances in postoperative diagnosis methods, the surgical treatment of endophthalmitis has had significant improvements in vitrectomy techniques, and in many cases, it has been proposed as the first-line treatment concomitantly with intravitreal antibiotic therapy. Moreover, there is increasing evidence that prophylaxis with intracameral antibiotic therapy further decreases postoperative endophthalmitis incidence

Long-Term Dabigatran Treatment Delays Alzheimer's Disease Pathogenesis in the TgCRND8 Mouse Model

BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder with important vascular and hemostatic alterations that should be taken into account during diagnosis and treatment. OBJECTIVES: This study evaluates whether anticoagulation with dabigatran, a clinically approved oral direct thrombin inhibitor with a low risk of intracerebral hemorrhage, ameliorates AD pathogenesis in a transgenic mouse model of AD. METHODS: TgCRND8 AD mice and their wild-type littermates were treated for 1 year with dabigatran etexilate or placebo. Cognition was evaluated using the Barnes maze, and cerebral perfusion was examined by arterial spin labeling. At the molecular level, Western blot and histochemical analyses were performed to analyze fibrin content, amyloid burden, neuroinflammatory activity, and blood-brain barrier (BBB) integrity. RESULTS: Anticoagulation with dabigatran prevented memory decline, cerebral hypoperfusion, and toxic fibrin deposition in the AD mouse brain. In addition, long-term dabigatran treatment significantly reduced the extent of amyloid plaques, oligomers, phagocytic microglia, and infiltrated T cells by 23.7%, 51.8%, 31.3%, and 32.2%, respectively. Dabigatran anticoagulation also prevented AD-related astrogliosis and pericyte alterations, and maintained expression of the water channel aquaporin-4 at astrocytic perivascular endfeet of the BBB. CONCLUSIONS: Long-term anticoagulation with dabigatran inhibited thrombin and the formation of occlusive thrombi in AD; preserved cognition, cerebral perfusion, and BBB function; and ameliorated neuroinflammation and amyloid deposition in AD mice. Our results open a field for future investigation on whether the use of direct oral anticoagulants might be of therapeutic value in AD.This work was funded by a Proof-of-Concept Award from the Robertson Therapeutic Development Fund (Dr. Cortes-Canteli), The Rockefeller University; NINDS/NIH grant NIS106668 (Drs. Norris and Strickland); European Union’s Seventh Framework Programme (FP7-PEOPLE-2013-IIF), grant agreement n PIIF-GA-2013-624811 (Drs. Cortes-Canteli and Fuster), CNIC, Madrid, Spain; Miguel Servet type I research contract (CP16/00174 and MS16/00174 [Dr. Cortes-Canteli]), Instituto de Salud Carlos III (ISCIII), CNIC; Iniciativa de Empleo Juvenil (PEJ16/MED/TL-1231 [A. Marcos-Diaz] and PEJ-2018-AI/BMD-11477 [C. Ceron]) from Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid; European Regional Development Funds (FEDER “Una manera de hacer Europa”) and European Social Funds (FSE “El FSE invierte en tu futuro”); and with the support of the Marie Curie Alumni Association (Dr. Cortes-Canteli). The CNIC is supported by the ISCIII, the Spanish Ministerio de Ciencia, Innovación y Universidades (MCNU), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). CIC biomaGUNE is a Maria de Maeztu Unit of Excellence (MDM-2017-0720). Dr. Sanchez-Gonzalez is an employee of Philips Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

Safety profile and pharmacokinetic analyses of the anti-CTLA4 antibody tremelimumab administered as a one hour infusion

BACKGROUND: CTLA4 blocking monoclonal antibodies provide a low frequency but durable tumor responses in patients with metastatic melanoma, which led to the regulatory approval of ipilimumab based on two randomized clinical trials with overall survival advantage. The similarly fully human anti-CTLA4 antibody tremelimumab had been developed in the clinic at a fixed rate infusion, resulting in very prolonged infusion times. A new formulation of tremelimumab allowed testing a shorter infusion time. METHODS: A phase 1 multi-center study to establish the safety and tolerability of administering tremelimumab as a 1-hour infusion to patients with metastatic melanoma. Secondary endpoints included pharmacokinetic and clinical effects of tremelimumab. RESULTS: No grade 3 or greater infusion-related adverse events or other adverse events preventing the administration of the full tremelimumab dose were noted in 44 treated patients. The overall side effect profile was consistent with prior experiences with anti-CTLA4 antibodies. Objective tumor responses were noted in 11% of evaluable patients with metastatic melanoma, which is also consistent with the prior experience with CTLA4 antagonistic antibodies. CONCLUSIONS: This study did not identify any safety concerns when tremelimumab was administered as a 1-hour infusion. These data support further clinical testing of the 1-hour infusion of tremelimumab. (Clinical trial registration number NCT00585000)

Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer

BACKGROUND: Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. METHODS: Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. RESULTS: Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. CONCLUSION: Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed

New and confirmed records of fishes from the Cabo Verde archipelago based on photographic and genetic data

In recent decades the Cabo Verde ichthyofauna has been studied more extensively, and nowadays photo-recording is employed as a valuable asset under special caution and consideration. Four species reported here are new records for Cabo Verde: Carlarius sp., sea catfish; Serranus cabrilla, comber; Branchiostegus semifasciatus, African tilefish and Lutjanus dentatus, African coastal snapper. The presence in Cabo Verde of Glaucostegus cemiculus, blackchin guitarfish; Elops senegalensis, Senegalese ladyfish; Lophius spp., bathydemersal monkfishes; Rachycentron canadum, cobia; Pagrus auriga, African seabream; Lutjanus dentatus, African coastal snapper and Mugil cephalus, grey mullet, was re-confirmed by photo-records. Squalus megalops, cosmopolitan spurdog, was identified by genetic fingerprinting. The, two littoral species, P. auriga and M. cephalus, are firmly established in the archipelago and additional information on their occurrence is given. The findings reported in the present contribution may well be the result of a wider sharing of information between fishermen and other seafarers and scientists, rather than an indicator of recent faunal changes

Use of Dried Blood Spots to Elucidate Full-Length Transmitted/Founder HIV-1 Genomes.

BACKGROUND: Identification of HIV-1 genomes responsible for establishing clinical infection in newly infected individuals is fundamental to prevention and pathogenesis research. Processing, storage, and transportation of the clinical samples required to perform these virologic assays in resource-limited settings requires challenging venipuncture and cold chain logistics. Here, we validate the use of dried-blood spots (DBS) as a simple and convenient alternative to collecting and storing frozen plasma. METHODS: We performed parallel nucleic acid extraction, single genome amplification (SGA), next generation sequencing (NGS), and phylogenetic analyses on plasma and DBS. RESULTS: We demonstrated the capacity to extract viral RNA from DBS and perform SGA to infer the complete nucleotide sequence of the transmitted/founder (TF) HIV-1 envelope gene and full-length genome in two acutely infected individuals. Using both SGA and NGS methodologies, we showed that sequences generated from DBS and plasma display comparable phylogenetic patterns in both acute and chronic infection. SGA was successful on samples with a range of plasma viremia, including samples as low as 1,700 copies/ml and an estimated ∼50 viral copies per blood spot. Further, we demonstrated reproducible efficiency in gp160 env sequencing in DBS stored at ambient temperature for up to three weeks or at -20°C for up to five months. CONCLUSIONS: These findings support the use of DBS as a practical and cost-effective alternative to frozen plasma for clinical trials and translational research conducted in resource-limited settings

High Multiplicity Infection by HIV-1 in Men Who Have Sex with Men

Elucidating virus-host interactions responsible for HIV-1 transmission is important for advancing HIV-1 prevention strategies. To this end, single genome amplification (SGA) and sequencing of HIV-1 within the context of a model of random virus evolution has made possible for the first time an unambiguous identification of transmitted/founder viruses and a precise estimation of their numbers. Here, we applied this approach to HIV-1 env analyses in a cohort of acutely infected men who have sex with men (MSM) and found that a high proportion (10 of 28; 36%) had been productively infected by more than one virus. In subjects with multivariant transmission, the minimum number of transmitted viruses ranged from 2 to 10 with viral recombination leading to rapid and extensive genetic shuffling among virus lineages. A combined analysis of these results, together with recently published findings based on identical SGA methods in largely heterosexual (HSX) cohorts, revealed a significantly higher frequency of multivariant transmission in MSM than in HSX [19 of 50 subjects (38%) versus 34 of 175 subjects (19%); Fisher's exact p = 0.008]. To further evaluate the SGA strategy for identifying transmitted/founder viruses, we analyzed 239 overlapping 5′ and 3′ half genome or env-only sequences from plasma viral RNA (vRNA) and blood mononuclear cell DNA in an MSM subject who had a particularly well-documented virus exposure history 3–6 days before symptom onset and 14–17 days before peak plasma viremia (47,600,000 vRNA molecules/ml). All 239 sequences coalesced to a single transmitted/founder virus genome in a time frame consistent with the clinical history, and a molecular clone of this genome encoded replication competent virus in accord with model predictions. Higher multiplicity of HIV-1 infection in MSM compared with HSX is consistent with the demonstrably higher epidemiological risk of virus acquisition in MSM and could indicate a greater challenge for HIV-1 vaccines than previously recognized