A 12-month prospective trial of inject and extend regimen for ranibizumab treatment of age-related macular degeneration.

PURPOSE: To evaluate the safety and efficacy of a strictly applied inject and extend protocol for ranibizumab treatment of age-related macular degeneration. METHODS: This is a prospective, multicenter, nonrandomized trial. Patients underwent standard induction with 3 intravitreal doses of 0.5 mg ranibizumab, each 1 month apart. Following this induction, patients were evaluated and received an injection at each visit. If they did not meet set criteria for signs of exudative disease the interval to the next visit was extended by 2 weeks and if exudative disease was present the interval was shortened by 2 weeks. RESULTS: Vision improved by 1.3 lines (P = 0.008); 26% gained ≥3 lines of vision, 74% lost no lines of vision, and 95% avoided loss of ≥3 lines of vision. CONCLUSION: This study shows that the Inject and Extend protocol is safe and efficacious for the treatment of age-related macular degeneration. Head-to-head studies are needed to compare directly with other regimens currently in use, as well as economic analysis to investigate the financial implications.

Purification of ß-lactoglobulin with a high-capacity anion exchanger: high-throughput process development and scale-up considerations.

BACKGROUND: ß-Lactoglobulin is the most abundant protein in bovine whey. It is a valuable nutriceutical with multiple physiological functions. There are many ongoing efforts to improve approaches by which this whey protein can be conveniently and economically purified in significant quantities. High-capacity resins for protein fractionation are currently available in the biotech industry. One such resin is evaluated in the present investigation. RESULTS: This work describes a high-capacity ion exchange chromatography method for one-column fractionation of ß-lactoglobulin from whey. It was obtained with a >90% purity. The dynamic binding capacity was measured in packed columns. Comparable value predicted on the basis of Langmuir isotherm analysis from batch adsorption data in a high-throughput 96-well format is shown. Scale-up considerations are discussed with respect to feed concentration and binding capacity. CONCLUSIONS: The feasibility of preparing purified ß-lactoglobulin with a single high-capacity anion exchanger step was demonstrated. A capacity of >200 mg mL(-1) was obtained. A significant improvement in productivity can be realized by a simultaneous increase of binding capacity and feed concentration.

pH-based cation exchange chromatography in the capture and elution of monoclonal antibodies.

Cation exchange chromatography separates adsorbed proteins by controlling the salt concentration or the mobile phase pH. This study examines the pH-based method for binding and elution of monoclonal antibodies (MAbs). Five different clones with isoelectric points from 6 to 9 were evaluated. We performed our studies using a new chromatography resin (Nuvia™ S), which has high binding capacity. A three-column process incorporating Nuvia S as a capture step was also demonstrated for the purification of MAb from tissue culture fluid. Chromatography performance of Nuvia S was demonstrated in a 50-cycle study.

Kelawakaju gen. nov., a new Asian lineage of marpissine jumping spiders (Araneae, Salticidae, Marpissina).

The genus Kelawakaju Maddison & Ruiz, gen. nov., is described for a lineage of bark-dwelling Asian marpissine jumping spiders that represent a dispersal to Eurasia separate from that of the Marpissa-Mendoza lineage, according to the phylogeny recovered from analysis of four gene regions. All species of Kelawakaju are new to science except Kelawakajufrenata (Simon, 1901), comb. nov., which is transferred from Ocrisiona Simon, 1901. Kelawakajufrenata is known from Hong Kong, Guangdong, Guangxi, and likely Taiwan. The five new species are Kelawakajumulu Maddison & Ruiz, sp. nov. (type species of Kelawakaju, from Sarawak, Malaysia, ♂♀), K.intexta Maddison & Ruiz, sp. nov. (from Sarawak, ♂), K.leucomelas Maddison & Ng, sp. nov. (Singapore and Johor Bahru, ♂♀), K.sahyadri Vishnudas, Maddison, & Sudhikumar, sp. nov. (India, ♂♀), and K.singapura Maddison & Ng, sp. nov. (Singapore, ♂♀).

Development of fluoroapatite chromatography for the purification of monoclonal antibody.

Monoclonal antibody was purified from tissue culture fluid using ceramic fluoroapatite chromatography. Efficiency of the capture step was shown to be sensitive to pH and phosphate concentration. More than 90% of host cell proteins were removed by ceramic fluoroapatite chromatography. Studies regarding pH control and metal adsorption are presented.

A phylogenetic and taxonomic review of baviine jumping spiders (Araneae, Salticidae, Baviini).

The systematics and taxonomy of the tropical Asian jumping spiders of the tribe Baviini is reviewed, with a molecular phylogenetic study (UCE sequence capture, traditional Sanger sequencing) guiding a reclassification of the group's genera. The well-studied members of the group are placed into six genera: Bavia Simon, 1877, Indopadilla Caleb & Sankaran, 2019, Padillothorax Simon, 1901, Piranthus Thorell, 1895, Stagetillus Simon, 1885, and one new genus, Maripanthus Maddison, gen. nov. The identity of Padillothorax is clarified, and Bavirecta Kanesharatnam & Benjamin, 2018 synonymized with it. Hyctiota Strand, 1911 is synonymized with Stagetillus. The molecular phylogeny divides the baviines into three clades, the Piranthus clade with a long embolus (Piranthus, Maripanthus), the genus Padillothorax with a flat body and short embolus, and the Bavia clade with a higher body and (usually) short embolus (remaining genera). In general, morphological synapomorphies support or extend the molecularly delimited groups. Eighteen new species are described: Bavia nessagyna, Indopadilla bamilin, I. kodagura, I. nesinor, I. redunca, I. redynis, I. sabivia, I. vimedaba, Maripanthus draconis (type species of Maripanthus), M. jubatus, M. reinholdae, Padillothorax badut, P. mulu, Piranthus api, P. bakau, P. kohi, P. mandai, and Stagetillus irri, all sp. nov., with taxonomic authority W. Maddison. The distinctions between baviines and the astioid Nungia Zabka, 1985 are reviewed, leading to four species being moved into Nungia from Bavia and other genera. Fifteen new combinations are established: Bavia maurerae (Freudenschuss & Seiter, 2016), Indopadilla annamita (Simon, 1903), I. kahariana (Prószynski & Deeleman-Reinhold, 2013), I. sonsorol (Berry, Beatty & Prószynski, 1997), I. suhartoi (Prószynski & Deeleman-Reinhold, 2013), Maripanthus menghaiensis (Cao & Li, 2016), M. smedleyi (Reimoser, 1929), Nungia hatamensis (Thorell, 1881), N. modesta (Keyserling, 1883), N. papakula (Strand, 1911), N. xiaolonghaensis (Cao & Li, 2016), Padillothorax casteti (Simon, 1900), P. exilis (Cao & Li, 2016), P. flavopunctus (Kanesharatnam & Benjamin, 2018), Stagetillus banda (Strand, 1911), all comb. nov. One combination is restored, Bavia capistrata (C. L. Koch, 1846). Five of these new or restored combinations correct previous errors of placing species in genera that have superficially similar palps but extremely different body forms, in fact belonging in distantly related tribes, emphasizing that the general shape of male palps should be used with caution in determining relationships. A little-studied genus, Padillothorus Prószynski, 2018, is tentatively assigned to the Baviini. Ligdus Thorell, 1895 is assigned to the Ballini.

PEG enhances viral clearance on ceramic hydroxyapatite.

Viral clearance across ceramic hydroxyapatite (CHT) was examined in two elution systems: sodium chloride and sodium chloride plus poly(ethylene glycol) (PEG). In both cases clearance of xenotropic murine leukemia virus was significant (3-4 log) while that of minute virus of mice varied between 1.7 and 2.7 log; in addition, the addition of PEG to the elution buffer enhanced viral clearance. The data are in agreement with the previous results and demonstrate that additional clearance can be obtained by adding PEG to a ceramic hydroxyapatite buffer system.

Geosesarma spectrum, a new species of semiterrestrial vampire crab (Crustacea: Decapoda: Brachyura: Sesarmidae) from Brunei Darussalam, Borneo.

A new semiterrestrial vampire crab from the family Sesarmidae, Geosesarma spectrum n. sp., is described from Brunei Darussalam (Borneo). The new species is characterised by its colouration in life, relatively large size, and form of the carapace, ambulatory legs and gonopods. The new species is compared to its closest congeners from Borneo. This description brings the number of Geosesarma species to 60.

Effect of Ranibizumab and Aflibercept on Best-Corrected Visual Acuity in Treat-and-Extend for Neovascular Age-Related Macular Degeneration: A Randomized Clinical Trial.

Importance: To our knowledge, this is the first randomized clinical trial to compare visual outcomes and injection loads between ranibizumab and aflibercept using an identical treat-and-extend (TE) regimen for neovascular age-related macular degeneration (nAMD). Objective: To report the results of the preplanned 12-month interim analysis of 2 predefined secondary efficacy end points of a randomized clinical trial. Design, Setting, and Participants: The Comparison of Ranibizumab and Aflibercept for the Development of Geographic Atrophy in (Wet) AMD Patients (RIVAL) trial was conducted in 24 sites in Australia and included 281 treatment-naive eyes from 281 participants with active choroidal neovascularization secondary to nAMD and a visual acuity letter score of 23 or greater who were recruited between April 11, 2014, and October 31, 2015. A preplanned interim analysis was performed at month 12. Best-corrected visual acuity (BCVA) assessors and the central reading center, which determined treatment intervals, were masked to treatment assignments. Interventions: Participants were randomized (1:1) to receive intravitreal injections of 0.5 mg of ranibizumab or 2.0 mg of aflibercept. After receiving 3 initial monthly injections, participants entered the TE phase. Main Outcomes and Measures: Mean change in BCVA and the number of injections from baseline to month 12. Results: Of 281 participants, 148 (52.7%) were women and the mean (SD) age was 77.7 (8.1) years. The baseline mean BCVA letter score (approximate Snellen equivalent) was 65.3 (20/50) in the ranibizumab arm and 65.1 (20/50) in the aflibercept arm. One hundred twenty-seven ranibizumab participants (90.1%) and 121 aflibercept participants (88.3%) completed month 12 with a mean (SD [Snellen equivalent]) BCVA letter score of 72.9 (15.5 [20/32]) and 70.5 (14.6 [20/40]), respectively. The mean change in BCVA letter scores from baseline to month 12 was 7.2 (95% CI, 5.5-8.9) for ranibizumab and 4.9 (95% CI, 3.1-6.6) for aflibercept (letter score difference, 2.3; 95% CI, -0.1 to 4.7; P = .06). The mean number of injections from baseline to month 12 was 9.7 in both the ranibizumab (SD, 2.8) and aflibercept (SD, 2.6) arms with a rate ratio of 1.00 (95% CI, 1.0-1.1; P = .86). Conclusions and Relevance: Our findings suggest that neither aflibercept nor ranibizumab for nAMD are superior to the other regarding the average visual acuity gains and number of injections during 1 year in a TE regimen. Further follow-up to 2 years may determine if advantages of one over the other can be identified. Trial Registration: Clinicaltrials.Gov identifier: NCT02130024.

Advanced abdominal pregnancy resulting from late uterine rupture.

BACKGROUND: Advanced abdominal pregnancy is rare, and one that occurs after uterine rupture with delivery of a viable fetus is exceptional. CASE: A multiparous patient was admitted at 29 weeks of gestation for conservative management of placenta previa. She complained of intermittent abdominal pain, but repeated assessment suggested that both the patient and the fetus were doing well. At 36 weeks, an abdominal pregnancy was diagnosed with radiological features suggestive of uterine rupture. Laparotomy was performed and a healthy infant was delivered. CONCLUSION: Fetal viability was achieved in this case of abdominal pregnancy secondary to uterine rupture after close maternal and fetal surveillance.

Improvement in eGFR in patients with chronic kidney disease attending a nephrology clinic.

BACKGROUND: The adverse effects arising from late referral to a nephrologist of patients with chronic kidney disease (CKD) are well known. Retrospectively we examined the initial characteristics of patients referred in various stages of CKD to our nephrology division and tried to identify potential baseline factors associated with subsequent changes in estimated glomerular filtration rate (eGFR). PATIENTS AND METHODS: Between September 1997 and June 2006 1,443 patients (909 male, 534 female) with CKD, with eGFRs ranging from 15 to 89 ml/min, were referred to our nephrology division and categorized using the National Kidney Foundation classification for CKD based on eGFR. The slope of eGFR change (ml/min-1/1.73/m2-1/year-1) was determined by linear regression analysis and the patients were divided into five groups: (1) significantly progressive slope (deterioration) (more negative than -5 ml/min/year); (2) mildly progressive slope (>-5 to -1 to +1 to or=+5). RESULTS: At the first nephrology referral, 5.8% of the patients were on CKD stage 2 (eGFR: 90-60 ml/m), 46.7% on CKD stage 3 (eGFR: 59-30 ml/m), and 47.5% on CKD stage 4 (eGFR: 29-15 ml/m) CKD. Significantly improved slope was detected in 48.2% of CKD stage 2 patients, 29.3% of CKD stage 3 patients, and only 14.7% of CKD stage 4 patients (P<0.05). Being in stage 4 or stage 3 versus being in stage 2 significantly reduced the likelihood of an improved slope in logistic regression analysis whereas age, gender, presence of hypertension, and diabetes mellitus did not reach the level of significance. CONCLUSION: Referral to a nephrology clinic can lead not only to arrest of progression of CKD but also to regression/improvement. Early referral is a positive predictive factor for improvement in eGFR, which emphasizes the importance of such referral. The previously held idea that, once established, CKD progresses invariably is not valid anymore.

The freshwater crabs of Danum Valley Conservation Area in Sabah, East Malaysia, with a description of a new species of Thelphusula Bott, 1969 (Crustacea, Brachyura, Gecarcinucidae, Potamidae, Sesarmidae).

Seven species of freshwater crabs from three families are recorded from and around the Danum Valley Conservation Area in Sabah, Malaysian Borneo: Thelphusula capillodigitussp. n., Thelphusula dicerophilus Ng & Stuebing, 1990, Arachnothelphusa terrapes Ng, 1991, Terrathelphusa secula Ng & Tan, 2015, Parathelphusa valida Ng & Goh, 1987 (new record) (Gecarcinucidae); Isolapotamon ingeri Ng & Tan, 1998 (Potamidae); and Geosesarma danumense Ng, 2002 (Sesarmidae). The new species of Thelphusula Bott, 1979, can be distinguished from all congeners by a unique combination of morphological features, most notably the presence of dense patches of short setae on the fingers of the adult male chelipeds, as well as the structure of the male first gonopod. Arachnothelphusa terrapes is confirmed to be a phytotelm species. A key to all species in the conservation area is provided.

Costs and Effectiveness of Interventions to Reduce Motor Vehicle-Related Injuries and Deaths: Supplement to Tool Documentation.

Motor vehicle crashes account for a large number of deaths and injuries. In the United States, in 2015, more than 35,000 people were killed and approximately 2.44 million were injured in motor vehicle crashes. In 2010, the economic costs associated with motor vehicle crashes in the United States were substantial, estimated to be $242 billion. Fortunately, a wide range of evidence-based interventions, including both policies and programs, can help prevent motor vehicle-related injuries and deaths. In 2014, RAND researchers developed an online tool, the Motor Vehicle Prioritizing Interventions and Cost Calculator for States (MV PICCS), to help determine the costs and effectiveness of various interventions to reduce injuries and deaths from motor vehicle crashes and what interventions together generate the largest reductions in injuries and deaths for a given implementation budget. A 2015 update added two new interventions and produced a series of reports about allocating traffic safety funds. The 2017 update, MV PICCS 3.0, determined whether to add new interventions, updated information on the interventions' effectiveness and costs, and redesigned the tool's user interface to be more user-friendly.

Mechanistic model for adsorption of immunoglobulin on hydroxyapatite.

A model is developed for correlating the adsorption of protein to hydroxyapatite in terms of pH, phosphate and imidazole. It provides a basis for manipulating the chromatography conditions so as to obtain the best possible fractionation. The adsorption mechanism is apparently a function of two calcium affinity interactions and cation exchange. We used immunoglobulins and a fusion protein with or without a poly(6)histidine tag for our investigation. The results are presented and discussed in the present study.

Comparative evaluation of aspheric toric intraocular lens implantation and limbal relaxing incisions in eyes with cataracts and ≤3 dioptres of astigmatism.

PURPOSE: To compare the visual outcomes of aspheric toric intraocular lens (IOL) implantation and limbal relaxing incisions (LRI) for management of coexisting age-related cataracts and astigmatism. METHODS: In this prospective study, sixty eyes of 60 patients with visually significant cataract and coexisting corneal astigmatism ≤3 dioptres (D) were randomised to undergo phacoemulsification with either aspheric toric IOL or aspheric monofocal IOL with LRI. The main outcome measures were postoperative 3-month uncorrected visual acuity (UCVA), contrast sensitivity, rotational stability of the toric IOL and spectacle independence. RESULTS: The postoperative UCVA, contrast sensitivity and refractive astigmatism were significantly better than the baseline measurements for both groups (p≤0.001). There was no significant difference detected for these parameters between LRI and toric IOL groups postoperatively (p≥0.119). At both postoperative month 1 and 3, the percentages of eyes in need of spectacles were lower in toric group than LRI group (p≤0.030). IOL misalignment was noted in three eyes in the toric IOL group (mean misalignment 7.67±4.04°). On vector analysis, magnitude of error (ME) was negative in the LRI group indicating undercorrection, whereas the ME was close to zero for toric group. CONCLUSIONS: Both toric IOL implantation and LRI were effective in correcting corneal astigmatism ≤3 D during phacoemulsification, while LRI tended to undercorrect astigmatism.

Change in Tear Film Lipid Layer Thickness, Corneal Thickness, Volume and Topography after Superficial Cauterization for Conjunctivochalasis.

We evaluated the change in tear film lipid layer thickness, corneal thickness, volume and topography after superficial cauterization of symptomatic conjunctivochalasis. Bilateral superficial conjunctival cauterization was performed in 36 eyes of 18 patients with symptomatic conjunctivochalasis. The mean age of patients (12 males, 6 females) was 68.6 ± 10.9 years (range: 44-83 years). Preoperatively, 28 eyes (77.8%) had grade 1 conjunctivochalasis, and 8 eyes (22.2%) had grade 2 conjunctivochalasis. At 1 month postoperatively, the severity of conjunctivochalasis decreased significantly (p < 0.001) and 29 eyes (80.6%) had grade 0 conjunctivochalasis whereas 7 eyes (19.4%) had grade 1 conjunctivochalasis. The mean Ocular Surface Disease Index score decreased from 31.5 ± 15.2 preoperatively to 21.5 ± 14.2 at the end of 1 month postoperatively (p = 0.001). There was a statistically significant increase in mean tear film lipid layer thickness 1 month after the surgery (49.6 ± 16.1 nm vs 62.6 ± 21.6 nm; p < 0.001). The central corneal thickness, thinnest corneal thickness and corneal volume decreased significantly postoperatively (p < 0.001). Our study showed that superficial conjunctival cauterization is an effective technique for management of conjunctivochalasis in the short term. An increase in tear film lipid layer thickness along with a decrease in corneal thickness and volume were observed after surgical correction of conjunctivochalasis.

Optical quality assessment in normal and forme fruste keratoconus eyes with a double-pass system: a comparison and variability study.

PURPOSE: To comparatively evaluate the image quality in normal and forme fruste keratoconus patients using a double-pass system. METHODS: Fourteen normal eyes and 15 eyes with forme fruste keratoconus were included. Corneal tomographic parameters were obtained with optical coherence tomography. Image quality characteristics were determined by an optical quality analysis system (OQAS). Two readings were obtained from each eye. The following parameters were analysed: modulation transfer function cutoff frequency (MTF), Strehl ratio and OQAS values (OV) at contrasts of 100% (OV-100), 20% (OV-20) and 9% (OV-9). Repeatability coefficient (RC), coefficient of variation (CVw) and intraclass correlation coefficient (ICC) were evaluated. RESULTS: There were no significant differences in central corneal thickness, anterior best-fit sphere and posterior best-fit sphere in both groups. There was a significant difference between the mean MTF (p=0.001), Strehl ratio (p<0.001), OV-100 (p=0.001), OV-20 (p<0.001) and OV-9 (p<0.001) values between both groups. The coefficients of variation were 4.10 (MTF) and 13.77 (Strehl ratio) in normal eyes and 14.53 (MTF) and 14.97 (Strehl ratio) in eyes with forme fruste keratoconus. The ICC values were 0.99 and 0.95 for MTF and, 0.80 and 0.91 for Strehl ratio, in normal and forme fruste keratoconus eyes, respectively. The corresponding repeatability values were 3.53 and 6.15 for MTF and, 0.06 and 0.04 for Strehl ratio, respectively. CONCLUSIONS: OQAS has the potential to be a useful diagnostic tool in cases with early keratoconus. The repeatability of a double-pass (DP) system was good in normal as well as forme fruste keratoconus eyes.

Design of Wrist Gimbal: a forearm and wrist exoskeleton for stroke rehabilitation.

In this paper, we present design, implementation and specifications of the Wrist Gimbal, a three degree-of-freedom (DOF) exoskeleton developed for forearm and wrist rehabilitation. Wrist Gimbal has three active DOF, corresponding to pronation/supination, flexion/extension and adduction/abduction joints. We mainly focused on a robust, safe and practical device design to facilitate clinical implementation, testing and acceptance. Robustness and mechanical rigidity was achieved by implementing two bearing supports for each of the pronation/supination and adduction/abduction axes. Rubber hard stops for each axis, an emergency stop button and software measures ensured safe operation. An arm rest with padding and straps, a handle with adjustable distal distance and height and a large inner volume contribute to ease of use, of patient attachment and to comfort. We present the specifications of Wrist Gimbal in comparison with similar devices in the literature and example data collected from a healthy subject.

Variability in CKD stage in outpatients followed in two large renal clinics.

OBJECTIVE: Chronic kidney disease (CKD) is staged by glomerular filtration rate (GFR). CKD stages sometimes vary between routine office visits, and it is unknown if this impacts renal and patient survival separately from a cross-sectional CKD stage value. We quantified and categorized CKD stage variability in a large group of outpatients and correlated this with clinical and demographic features and with renal and patient survival. METHODS: All estimated GFRs were staged in the first observation period. CKD stages were then categorized as static, improving, worsening, or fluctuating. Logistic regression analysis was performed to identify clinical variables associated with CKD stage variability. Death and dialysis progression rates were then collected and analyzed using Cox proportional regression. RESULTS: During a 1.1-year observation period, 1,262 patients (mean age 71.25 years) had a mean 5 eGFR's. CKD stages were static in 60.4%, worsened in 14.4%, improved in 7.4%, and fluctuated in 17.2% of patients. Secondary analysis revealed heavy proteinuria and East Asian ethnicity to be negatively, and diabetes mellitus and previous acute kidney injury to be positively associated with improving CKD stages. Cox proportional regression of 902 patients analyzed 2.3 years later revealed a negative association with improving CKD stage and subsequent need for dialysis. CONCLUSIONS: CKD stage changed in 40% of 1,262 elderly patients when determined 5 times in just over 1 year. Improving CKD stage was the only variability pattern significantly associated with any of the clinical outcomes when assessed 2.3 years later, being unlikely to be linked with subsequent need for dialysis.

Purification of lactoferrin using hydroxyapatite.

Lactoferrin is an important nutriceutical with various physiological functions. It is present in whey at very low concentrations. This work describes a mixed-mode (hydroxyapatite) chromatography method for one-column fractionation of lactoferrin from whey. Lactoperoxidase, a protein with similar molecular weight and isoelectric point, was initially desorbed from the matrix under isocratic conditions. Lactoferrin was obtained in homogeneity without lactoperoxidase activity and free from other major whey proteins such as alpha lactoalbumin and beta lactoglobulin.