Both natural influenza infection and current seasonal influenza vaccines primarily induce neutralizing antibody responses against highly diverse epitopes within the "head" of the viral hemagglutinin ...(HA) protein. There is increasing interest in redirecting immunity toward the more conserved HA stem or stalk as a means of broadening protective antibody responses. Here we examined HA stem-specific B cell and T follicular helper (Tfh) cell responses in the context of influenza infection and immunization in mouse and monkey models. We found that during infection, the stem domain was immunologically subdominant to the head in terms of serum antibody production and antigen-specific B and Tfh cell responses. Similarly, we found that HA stem immunogens were poorly immunogenic compared with the full-length HA with abolished sialic acid binding activity, with limiting Tfh cell elicitation a potential constraint to the induction or boosting of anti-stem immunity by vaccination. Finally, we confirm that currently licensed seasonal influenza vaccines can boost preexisting memory responses against the HA stem in humans. An increased understanding of the immune dynamics surrounding the HA stem is essential to inform the design of next-generation influenza vaccines for broad and durable protection.
The domestic ferret (Mustela putorius furo) provides a critical animal model to study human respiratory diseases. However immunological insights are restricted due to a lack of ferret-specific ...reagents and limited genetic information about ferret B and T cell receptors. Here, variable, diversity and joining genes within the ferret kappa, lambda and heavy chain immunoglobulin loci were annotated using available genomic information. A multiplex PCR approach was derived that facilitated the recovery of paired heavy and light chain immunoglobulin sequences from single sorted ferret B cells, allowing validation of predicted germline gene sequences and the identification of putative novel germlines. Eukaryotic expression vectors were developed that enabled the generation of recombinant ferret monoclonal antibodies. This work advances the ferret as an informative immunological model for viral diseases by allowing the in-depth interrogation of antibody-based immunity.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The ferret is a key animal model for investigating the pathogenicity and transmissibility of important human viruses, and for the pre-clinical assessment of vaccines. However, relatively little is ...known about the ferret immune system, due in part to a paucity of ferret-reactive reagents. In particular, T follicular helper (Tfh) cells are critical in the generation of effective humoral responses in humans, mice and other animal models but to date it has not been possible to identify Tfh in ferrets. Here, we describe the screening and development of ferret-reactive BCL6, CXCR5 and PD-1 monoclonal antibodies. We found two commercial anti-BCL6 antibodies (clone K112-91 and clone IG191E/A8) had cross-reactivity with lymph node cells from influenza-infected ferrets. We next developed two murine monoclonal antibodies against ferret CXCR5 (clone feX5-C05) and PD-1 (clone fePD-CL1) using a single B cell PCR-based method. We were able to clearly identify Tfh cells in lymph nodes from influenza infected ferrets using these antibodies. The development of ferret Tfh marker antibodies and the identification of ferret Tfh cells will assist the evaluation of vaccine-induced Tfh responses in the ferret model and the design of novel vaccines against the infection of influenza and other viruses, including SARS-CoV2.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
This study investigates whether the application of Hemopatch, a novel hemostatic patch, could prevent lymphatic leak after robotic-assisted radical prostatectomy (RARP) and bilateral pelvic lymph ...node dissection (BPLND). This is a prospective, single-center, phase III randomized controlled trial investigating the efficacy of Hemopatch in preventing lymphatic leak after RARP and BPLND. Participants were randomized to receive RARP and BPLND, with or without the use of Hemopatch, with an allocation ratio of 1:1. The primary outcome is the total drain output volume. The secondary outcomes include blood loss, operative time, lymph node yield, duration of drainage, drain output per day, hospital stay, transfusion and 30-day complications. A total of 32 patients were recruited in the study. The Hemopatch group had a significantly lower median total drain output than the control group (35 mL vs. 180 mL, p = 0.022) and a significantly lower drain output volume per day compared to the control group (35 mL/day vs. 89 mL/day, p = 0.038). There was no significant difference in the other secondary outcomes. In conclusion, the application of Hemopatch in RARP and BPLND could reduce the total drain output volume and the drain output volume per day. The use of Hemopatch should be considered to prevent lymphatic leakage after RARP and BPLND.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Ferrets are a well‐established model for studying both the pathogenesis and transmission of human respiratory viruses and evaluation of antiviral vaccines. Advanced immunological studies would add ...substantial value to the ferret models of disease but are hindered by the low number of ferret‐reactive reagents available for flow cytometry and immunohistochemistry. Nevertheless, progress has been made to understand immune responses in the ferret model with a limited set of ferret‐specific reagents and assays. This review examines current immunological insights gained from the ferret model across relevant human respiratory diseases, with a focus on influenza viruses. We highlight key knowledge gaps that need to be bridged to advance the utility of ferrets for immunological studies.
Full text
Available for:
FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
There is no gold standard protocol for total number of cores required in any patient; it is dictated by hospital policy, availability of resources, and the experience of the urologist. The ...instruments used during the procedure comprised an ultrasound machine with long side-fire sensor probe, a bed with two leg supports to facilitate lithotomy position, one disposable biopsy gun, two needles for local anaesthesia, two metal trocars, and eight specimen bottles. Ethics approval This study was approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Clinical Research Ethics Committee (Ref CREC 2018.323).
Full text
Available for:
FFLJ, NUK, ODKLJ, UL, UM, UPUK
To compare the clinical outcomes and pathological findings of transperineal ultrasound-guided prostate biopsy (TPUSPB) and transrectal ultrasound-guided prostate biopsy (TRUSPB) in a secondary ...referral hospital.
This was a retrospective study of 100 TPUSPBs and 100 TRUSPBs performed in our centre. Pre-biopsy patient parameters (eg, patient age, clinical staging, serum prostate-specific antigen PSA level, prostate size, and PSA density), as well as pathological results and 30-day complication and readmission rates, were retrieved from the patients' medical records and compared between the two groups.
One hundred TPUSPBs performed from January 2018 to May 2018 and 100 TRUSPBs performed from January 2016 to April 2016 were included for analysis. Mean age did not significantly differ between the groups. The TPUSPB group had a higher mean PSA level, smaller prostate size, and higher PSA density, compared with the TRUSPB group. The overall prostate cancer detection rate was similar between the TPUSPB and TRUSPB groups (35% vs 25%, P=0.123). There were no significant differences between the groups in prostate cancer detection rates after stratification according to PSA density and clinical staging. With respect to complications, no patients developed fever in the TPUSPB group, while 4% of patients in the TRUSPB group had fever and required at least 1-week admission for intravenous antibiotic administration.
For prostate biopsy, TPUSPB is safer, with no infection complications, and has similar prostate cancer detection rate compared with TRUSPB.
Full text
Available for:
FFLJ, NUK, ODKLJ, UL, UM, UPUK
A number of research papers have used different types of similarity/dissimilarity coefficients for determining part families. In cellular manufacturing systems, most machines are capable of ...performing more than one operation, which makes parts rerouting feasible. When a part is rerouted, it affects the cell performance. Most of the suggested approaches in the literature develop a new similarity coefficient based on mathematical analysis, however, these methods tend to disregard alternative routes during machine failure. The main objective of this paper is to identify part families based on a new similarity coefficient which considers the number of alternative routes available during machine failure. Based on the new similarity coefficient, the part families were identified by using p-median model.
Full text
Available for:
IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Measures are important to organizational effectiveness and the topic of manufacturing performance measurement (MPM) has recently attracted considerable interest, however, there is little research on ...what constitutes an effective performance measurement (PM) system. Therefore, the main objective of this paper is to identify the critical characteristics of performance measures as a first step to design an effective MPM system. Throughout a survey of accounting, manufacturing, and managerial literature, different characteristics were found on a consistent basis. The identified set of characteristics can be used to evaluate and improve the measurement system. Also, following a set of guidelines for design performance measures would lead to excellent performance in today's highly turbulent and competitive business environment. The second objective is to establish a typology for performance measurement system by establishing the criteria and attributes of those characteristics. The criteria are measurement system, data, and measurement that can be used to select the performance dimensions and measures. The attributes are configuration, style, actionability, and information. The third objective is to propose a process for measure selection. This method can be used to select the appropriate measures based on the optimum characteristics of performance measures. PUBLICATION ABSTRACT
Although the research concerning cell formation (CF) with regard to similarity coefficients still centers on similarity coefficients between machines and machine cells and/or between parts and part ...families, a relationship between a new part and the existing manufacturing cells is still unexplored. In order to address this concept, a new similarity coefficient between the new part and existing manufacturing cells will be proposed. This similarity coefficient consists of two subsimilarity coefficients. The first subsimilarity coefficient is between the new part and the existing part family, and the other one is between the same new part and the existing machine cell associated with that part family. A complete analytical example will be presented to show the proposed similarity coefficient and how to accept one or more new parts (products). The results show that manufacturing cells can become agile systems. PUBLICATION ABSTRACT
PDF
