Venture Capitalists as gatekeepers for Biotechnological Innovation

Venture capitalists (VCs) aim at trade sales as a preferred exit-strategy for biotechnology companies they invest in. Therefore, VCs pay close attention to the wishes of larger (bio)pharmaceutical acquirers. In this paper we explore VCs’ behavior and strategies by analyzing the technology fields and therapeutic areas in which they are invested most and which yield the highest returns by means of trade sales. The data show that VCs are by far most invested in oncology and this is also an area in which relatively high returns are realized. Regarding other areas, VCs could balance their average investment valuations more in correspondence with what acquirers are willing to pay. In addition, VCs have formidable insight in the types of technologies that do well and they seem to employ a strategy focused on both short-term and long-term success. They are investing most in small molecule drugs and protein/peptide therapeutics, which both yield high returns, followed by DNA/RNA technologies which underlie the possibilities of personalized medicine. We conclude that Venture Capitalists act as technological gatekeepers because they are predicting long-term cure and care macro-trends.

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APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation

Hepatology International ◽

10.1007/s12072-019-09988-7 ◽

2019 ◽

Vol 13 (6) ◽

pp. 649-661 ◽

Cited By ~ 15

Author(s):

Tatsuo Kanda ◽

George K. K. Lau ◽

Lai Wei ◽

Mitsuhiko Moriyama ◽

Ming-Lung Yu ◽

...

Keyword(s):

Hbv Dna ◽

Hbv Reactivation ◽

Close Attention ◽

Short Term ◽

Direct Acting Antiviral ◽

B Virus ◽

Direct Acting ◽

Very High

Abstract In the direct-acting antiviral (DAA) era for hepatitis C virus (HCV) infection, sustained virological response (SVR) is very high, but close attention must be paid to the possible occurrence of hepatocellular carcinoma (HCC) and reactivation of hepatitis B virus (HBV) in patients with co-infection who achieved SVR in short term. HCC occurrence was more often observed in patients with previous HCC history. We found occurrence of HCC in 178 (29.6%) of 602 patients with previous HCC history (15.4 months mean follow-up post-DAA initiation) but, in contrast, in only 604 (1.3%) of 45,870 patients without previous HCC history (18.2 months mean follow-up). Thus, in these guidelines, we recommend the following: in patients with previous HCC history, surveillance at 4-month intervals for HCC by ultrasonography (US) and tumor markers should be performed. In patients without previous HCC history, surveillance at 6- to 12-month intervals for HCC including US is recommended until the long-term DAA treatment effects, especially for the resolution of liver fibrosis, are confirmed. This guideline also includes recommendations on how to follow-up patients who have been infected with both HCV and HBV. When HCV was eradicated in these HBsAg-positive patients or patients with previous HBV infection (anti-HBc and/or anti-HBs-positive), it was shown that HBV reactivation or HBV DNA reappearance was observed in 67 (41.4%) of 162 or 12 (0.9%) of 1317, respectively. For these co-infected patients, careful attention should be paid to HBV reactivation for 24 weeks post-treatment.

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THE TARGETED WAGE SUBSID Y: HOW PROGRAM DESIGN CREATES INCENTIVES FOR “CREAMING”

Just Labour ◽

10.25071/1705-1436.74 ◽

1969 ◽

Author(s):

Pam Lahey ◽

Peter V Hall

Keyword(s):

Program Design ◽

Target Population ◽

Close Attention ◽

Short Term ◽

Design Elements ◽

Employment Insurance ◽

Sustainable Employment ◽

The One ◽

Developed Nations

Across most developed nations, including Canada, parallel systems ofsocial welfare and employment insurance have increasingly been replaced byprograms that emphasize work as a meansto achieve welfare goals within theso-called re-employment framework. Various authors have drawn attention tothe tension between the goal of long-term sustainable employment, and re-employment-based strategies that emphasize short-term and stand-aloneinterventions. In this paper, we focus on the implementation of one suchprogram in Canada, the Targeted Wage Subsidy. This program seeks to place themost marginal qualifying participantsin employment by offering employers afinancial inducement. By paying close attention to the experiences of thosetasked with monitoring and implementing the program in Toronto, we identifyvarious ways in which program design elements may systematicallydisadvantage the intended recipients. These program delivery mechanisms areshaped both in the practices of implementing agents, as well as by the publicaccountability framework that enforces rigid timelines and reportingrequirements, resulting in a practicecommonly referred to by employmentservice providers as “creaming.” Our observations lead us to question whetherthe target population is, in fact, the one benefiting from these return-to-worksupports.

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Clinical application of a lung cancer organoid (tumoroid) culture system

npj Precision Oncology ◽

10.1038/s41698-021-00166-3 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Etsuko Yokota ◽

Miki Iwai ◽

Takuro Yukawa ◽

Masakazu Yoshida ◽

Yoshio Naomoto ◽

...

Keyword(s):

Lung Cancer ◽

Small Molecule ◽

Normal Lung ◽

High Expectations ◽

Long Term Culture ◽

Small Molecule Drugs ◽

Lung Epithelial ◽

Next Generation Sequencing Ngs ◽

Generation Sequencing

AbstractDespite high expectations for lung tumoroids, they have not been applied in the clinic due to the difficulty of their long-term culture. Here, however, using AO (airway organoid) media developed by the Clevers laboratory, we succeeded in generating 3 lung tumoroid lines for long-term culture (>13 months) from 41 lung cancer cases (primary or metastatic). Use of nutlin-3a was key to selecting lung tumoroids that harbor mutant p53 in order to eliminate normal lung epithelial organoids. Next-generation sequencing (NGS) analysis indicated that each lung tumoroid carried BRAFG469A, TPM3-ROS1 or EGFRL858R/RB1E737*, respectively. Targeted therapies using small molecule drugs (trametinib/erlotinib for BRAFG469A, crizotinib/entrectinib for TPM3-ROS1 and ABT-263/YM-155 for EGFRL858R/RB1E737*) significantly suppressed the growth of each lung tumoroid line. AO media was superior to 3 different media developed by other laboratories. Our experience indicates that long-term lung tumoroid culture is feasible, allowing us to identify NGS-based therapeutic targets and determine the responsiveness to corresponding small molecule drugs.

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Servitization in Support of Sustainable Cities: What Are Steel’s Contributions and Challenges?

Sustainability ◽

10.3390/su11030855 ◽

2019 ◽

Vol 11 (3) ◽

pp. 855 ◽

Cited By ~ 4

Author(s):

Julian Pinto ◽

Manuel Morales ◽

Mariia Fedoruk ◽

Marina Kovaleva ◽

Arnaud Diemer

Keyword(s):

Urban Metabolism ◽

Supply Side ◽

Sustainable Cities ◽

Close Attention ◽

Short Term ◽

Self Sufficiency ◽

Wide Range ◽

Environmental Goals ◽

Do So

In the pursuit of eco-efficiency, resilience, and self-sufficiency, sustainable cities focus on long-term environmental goals instead of only short-term economic ones. To do so, many of them rely on servitization, the practice of replacing tangible solutions for intangible ones. Considering steel’s wide range of applications and its pervasive presence, this article’s goal was twofold: Not only to understand how servitization helps sustainable cities, but also the contributions and challenges of the steel present in service-providing. To do so, the criteria of sustainable urban metabolism and circles of sustainability were used to analyze three case studies of servitization: energy, housing, and mobility. The results showed that servitization can provide significant benefits to sustainable cities, while also being able to substantially alter the supply-side dynamics of steelmaking by affecting, most notably, demand. This brought to light how important it is for steelmakers to pay close attention to the service-providing initiatives that may concern their clients and products. Nevertheless, further research is necessary to fully understand all of the effects that servitization can have on all of the commodities involved in its implementation.

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Suppression of HIF2 signalling attenuates the initiation of hypoxia-induced pulmonary hypertension

European Respiratory Journal ◽

10.1183/13993003.00378-2019 ◽

2019 ◽

pp. 1900378 ◽

Cited By ~ 14

Author(s):

Cheng-Jun Hu ◽

Jens M. Poth ◽

Hui Zhang ◽

Amanda Flockton ◽

Aya Laux ◽

...

Keyword(s):

Small Molecule ◽

Ventricular Hypertrophy ◽

Gene Deletion ◽

Cell Type ◽

Short Term ◽

Cell Type Specific ◽

Inducible Gene

Most published studies addressing the role of HIFs in hypoxia-induced PH development employ models that may not recapitulate the clinical setting, including the use of animals having pre-existing lung/vascular defects secondary to embryonic HIF ablation or activation. Further, critical questions including how and when HIF-signalling contributes to hypoxia-induced PH remains unanswered.Normal adult rodents in which global HIF1 or 2 was inhibited by inducible gene deletion or pharmacological inhibition (antisense oligonucleotides-ASO and small molecule inhibitors) were exposed to short-term (4 days) or chronic (4–5 weeks) hypoxia. Hemodynamic studies were performed, the animals euthanized and lungs and heart obtained for pathologic and transcriptomic analysis. Cell-type specific HIF signals for PH initiation were determined in normal pulmonary vascular cells in vitro and in mice (using cell-type specific HIF deletion).Global HIF1α deletion in mice did not prevent hypoxia-induced PH at 5 weeks. Mice with global HIF2α deletion did not survive long-term hypoxia. Partial HIF2α gene deletion, or HIF2-ASO (but not HIF1-ASO) reduced vessel muscularization, rises in pulmonary artery pressures and right ventricular hypertrophy in mice exposed to 4–5 week hypoxia. A small molecule HIF2 inhibitor (PT2567) significantly attenuated early events (monocyte recruitment and vascular cell proliferation) in rats exposed to 4-day hypoxia as well as vessel musculization, tenascin C accumulation and PH development in rats exposed to 5 week hypoxia. In vitro, HIF2 induced a distinct set of genes in normal pulmonary vascular EC, mediating inflammation and proliferation of EC and SMC. EC HIF2α knockout prevented hypoxia-induced PH in mice.Inhibition of HIF2, not HIF1 can provide a therapeutic approach to prevent the development of hypoxia-induced PH. Future studies are needed to investigate the role of HIFs in PH progression and reversal.

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Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

Behavioral and Brain Sciences ◽

10.1017/s0140525x15000928 ◽

2016 ◽

Vol 39 ◽

Author(s):

Mary C. Potter

Keyword(s):

Working Memory ◽

Rapid Serial Visual Presentation ◽

Language Comprehension ◽

Short Term Memory ◽

Visual Presentation ◽

Long Term Memory ◽

Short Term ◽

Term Memory ◽

Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

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Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159412 ◽

1990 ◽

Vol 48 (3) ◽

pp. 374-375

Author(s):

D.E. Loudy ◽

J. Sprinkle-Cavallo ◽

J.T. Yarrington ◽

F.Y. Thompson ◽

J.P. Gibson

Keyword(s):

Antidepressant Drug ◽

Beagle Dogs ◽

Long Term Effects ◽

Short Term ◽

Platelet Counts ◽

Toxicological Studies ◽

Induced Aggregation ◽

Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

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Comparison of Auditory, Language, Memory, and Attention Abilities in Children With and Without Listening Difficulties

American Journal of Audiology ◽

10.1044/2020_aja-20-00018 ◽

2020 ◽

Vol 29 (4) ◽

pp. 710-727

Author(s):

Beula M. Magimairaj ◽

Naveen K. Nagaraj ◽

Alexander V. Sergeev ◽

Natalie J. Benafield

Keyword(s):

Auditory Processing ◽

Short Term Memory ◽

Group Differences ◽

Long Term Memory ◽

Short Term ◽

Significant Group ◽

Term Memory ◽

Memory And Attention ◽

Speed And Accuracy

Objectives School-age children with and without parent-reported listening difficulties (LiD) were compared on auditory processing, language, memory, and attention abilities. The objective was to extend what is known so far in the literature about children with LiD by using multiple measures and selective novel measures across the above areas. Design Twenty-six children who were reported by their parents as having LiD and 26 age-matched typically developing children completed clinical tests of auditory processing and multiple measures of language, attention, and memory. All children had normal-range pure-tone hearing thresholds bilaterally. Group differences were examined. Results In addition to significantly poorer speech-perception-in-noise scores, children with LiD had reduced speed and accuracy of word retrieval from long-term memory, poorer short-term memory, sentence recall, and inferencing ability. Statistically significant group differences were of moderate effect size; however, standard test scores of children with LiD were not clinically poor. No statistically significant group differences were observed in attention, working memory capacity, vocabulary, and nonverbal IQ. Conclusions Mild signal-to-noise ratio loss, as reflected by the group mean of children with LiD, supported the children's functional listening problems. In addition, children's relative weakness in select areas of language performance, short-term memory, and long-term memory lexical retrieval speed and accuracy added to previous research on evidence-based areas that need to be evaluated in children with LiD who almost always have heterogenous profiles. Importantly, the functional difficulties faced by children with LiD in relation to their test results indicated, to some extent, that commonly used assessments may not be adequately capturing the children's listening challenges. Supplemental Material https://doi.org/10.23641/asha.12808607

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