Alkyl carboxylic acids are ubiquitous in all facets of chemical science, from natural products to polymers, and represent an ideal starting material with which to forge new connections. This study ...demonstrates how the same activating principles used for decades to make simple C–N (amide) bonds from carboxylic acids with loss of water can be used to make C–C bonds through coupling with dialkylzinc reagents and loss of carbon dioxide. This disconnection strategy benefits from the use of a simple, inexpensive nickel catalyst and exhibits a remarkably broad scope across a range of substrates (>70 examples).
A new transformation is presented that enables chemists to couple simple alkyl carboxylic acids with aryl zinc reagents under Ni-catalysis. The success of this reaction hinges on the unique use of ...redox-active esters that allow one to employ such derivatives as alkyl halides surrogates. The chemistry exhibits broad substrate scope and features a high degree of practicality. The simple procedure and extremely inexpensive nature of both the substrates and pre-catalyst (NiCl2·6H2O, ca. $9.5/mol) bode well for the immediate widespread adoption of this method.
We analyse the impact of the Brexit announcement shock on UK exports of commercial services, using a synthetic control method (SCM) to create a counterfactual based upon other countries’ exports. Our ...analysis considers two alternative scenarios: in the first, the shock was based upon the referendum date of 23 June 2016. We do indeed find significant evidence of a treatment shock based upon this date, as exports after this date are approximately 7% below the synthetic counterfactual. This is driven by ‘other commercial services’: the smaller tourist sector actually had a positive shock. If we repeat the analysis with an earlier treatment, it becomes clear that divergence was already starting in the first half of 2015, around the time of the general election campaign, although services exports had a clearer shock after June 2016, roughly doubling the discrepancy. This finding supports the suggestion that there was already some fear of Brexit before the referendum result, and indicates the importance of considering an earlier start date in studies of the Brexit shock.
Fracture sequelae of the proximal part of the humerus are challenging conditions, and various treatment options have been described. The purpose of this multicenter study was to analyze the clinical ...and radiographic outcomes as well as the complications following semiconstrained reverse total shoulder arthroplasty for the treatment of nonunion of a surgical neck fracture of the proximal part of the humerus.
Thirty-two patients with a mean age of sixty-eight years (range, forty-eight to eighty-three years) managed with a reverse shoulder arthroplasty for the treatment of nonunion of a proximal humeral fracture were analyzed clinically and radiographically. The mean duration of follow-up was four years (range, two to twelve years). The Constant score, active shoulder mobility, all complications, and revision procedures were recorded.
The mean Constant score increased from 14.2 points (range, 2 to 35 points) to 46.6 points (range, 6 to 75 points) (p < 0.001). The mean shoulder flexion increased from 42.9° (range, 0° to 160°) to 109.7° (range, 0° to 170°) (p < 0.001), and the mean external rotation increased from 0.5° (range, -40° to 60°) to 13.1° (range, -30° to 60°) (p < 0.005). No component loosening occurred, but 50% (sixteen) of the patients had radiographic evidence of scapular notching. There were thirteen complications (41%) leading to nine revision surgical procedures (28%). The most common complication was a dislocation following reverse shoulder arthroplasty, which occurred in 34% (eleven) of the patients. An intraoperative resection of the humeral head fragment and the tuberosities was associated with increased risk of dislocation (p < 0.007).
Nonunions of the proximal part of the humerus can be treated with reverse shoulder arthroplasty. Although clinical outcomes improved significantly, we found an unacceptably high rate of dislocations associated with intraoperative resection of the tuberosities. The tuberosities and the attached rotator cuff should be preserved if possible to reduce the risk of dislocation after reverse total shoulder arthroplasty.
The treatment of fracture sequelae of the proximal part of the humerus in combination with posttraumatic arthritis is challenging. The reported results of treatment with anatomic shoulder ...arthroplasty are disappointing. The aim of this multicenter study was to analyze the clinical and radiographic results of reverse shoulder arthroplasty for treatment of posttraumatic sequelae of the proximal part of the humerus with malunion of the tuberosities.
This was a retrospective, multicenter study of 42 patients (42 shoulders) with the diagnosis of posttraumatic sequelae of the proximal part of the humerus with malunions of the tuberosities who were treated with reverse shoulder arthroplasty between 2000 and 2010. The mean age at the time of arthroplasty was 68 years (range, 27 to 83 years; median, 70 years). The dominant side was treated in 24 cases. The mean clinical and radiographic follow-up was 4 years (range, 2 to 13 years; median, 3.5 years). The Constant score including subgroups, shoulder flexion, rotation motion, and radiographs of the affected shoulders were analyzed before the surgical procedure and at the time of the latest follow-up. Patients categorized their postoperative results as very good, good, satisfactory, or unsatisfactory.
The mean Constant score increased from 19.7 points (range, 0 to 52 points) preoperatively to 54.9 points (range, 21 to 83 points) postoperatively (p < 0.0001). All of the subgroups of the Constant score also increased, as did active shoulder flexion and external rotation (all p < 0.0001). In one case, loosening of the humeral and glenoid components occurred. Scapular notching was present in 22 shoulders (52%) and was grade 1 in 12 cases, grade 2 in 4 cases, grade 3 in 2 cases, and grade 4 in 4 cases. Complications occurred in 4 patients (9.5%). Eighteen patients (43%) rated their result as very good, 19 (45%) rated their result as good, 4 (10%) rated their result as satisfactory, and one (2%) rated the result as unsatisfactory.
Reverse shoulder arthroplasty is a viable treatment option for type-4 proximal humeral fracture sequelae that cannot otherwise be treated with anatomic shoulder replacement.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
This Article details the development of the iron-catalyzed conversion of olefins to radicals and their subsequent use in the construction of C–C bonds. Optimization of a reductive diene cyclization ...led to the development of an intermolecular cross-coupling of electronically-differentiated donor and acceptor olefins. Although the substitution on the donor olefins was initially limited to alkyl and aryl groups, additional efforts culminated in the expansion of the scope of the substitution to various heteroatom-based functionalities, providing a unified olefin reactivity. A vinyl sulfone acceptor olefin was developed, which allowed for the efficient synthesis of sulfone adducts that could be used as branch points for further diversification. Moreover, this reactivity was extended into an olefin-based Minisci reaction to functionalize heterocyclic scaffolds. Finally, mechanistic studies resulted in a more thorough understanding of the reaction, giving rise to the development of a more efficient second-generation set of olefin cross-coupling conditions.
Challenges in the selective manipulation of functional groups (chemoselectivity) in organic synthesis have historically been overcome either by using reagents/catalysts that tunably interact with a ...substrate or through modification to shield undesired sites of reactivity (protecting groups). Although electrochemistry offers precise redox control to achieve unique chemoselectivity, this approach often becomes challenging in the presence of multiple redox-active functionalities. Historically, electrosynthesis has been performed almost solely by using direct current (DC). In contrast, applying alternating current (AC) has been known to change reaction outcomes considerably on an analytical scale but has rarely been strategically exploited for use in complex preparative organic synthesis. Here we show how a square waveform employed to deliver electric currentrapid alternating polarity (rAP)enables control over reaction outcomes in the chemoselective reduction of carbonyl compounds, one of the most widely used reaction manifolds. The reactivity observed cannot be recapitulated using DC electrolysis or chemical reagents. The synthetic value brought by this new method for controlling chemoselectivity is vividly demonstrated in the context of classical reactivity problems such as chiral auxiliary removal and cutting-edge medicinal chemistry topics such as the synthesis of PROTACs.
Uncemented press-fit humeral stems were developed with the goal of decreasing operative time, preserving bone stock, and easing revision. In recent years, short stems and stemless humeral implants ...have also become available. These press-fit humeral implants have varying designs that can lead to changes in stress distribution in the proximal humerus. Such stress shielding manifests as bony adaptations and may affect long-term functional outcome and the ability to perform revision. However, current studies of humeral fixation during total shoulder arthroplasty are complicated because a variety of classification systems have been used to report findings. The purpose of this report is to review the current literature on press-fit fixation of the humeral component during total shoulder arthroplasty and propose minimum requirements for radiographic descriptions of stress shielding.
Protein folding occurs as a set of transitions between structural states within an energy landscape. An oversimplified view of the folding process emerges when transiently populated states are ...undetected because of limited instrumental resolution. Using force spectroscopy optimized for 1-microsecond resolution, we reexamined the unfolding of individual bacteriorhodopsin molecules in native lipid bilayers. The experimental data reveal the unfolding pathway in unprecedented detail. Numerous newly detected intermediates—many separated by as few as two or three amino acids—exhibited complex dynamics, including frequent refolding and state occupancies of <10 μs. Equilibrium measurements between such states enabled the folding free-energy landscape to be deduced. These results sharpen the picture of the mechanical unfolding of membrane proteins and, more broadly, enable experimental access to previously obscured protein dynamics.
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