[Comment] Redefine statistical significance

The lack of reproducibility of scientific studies has caused growing concern over the credibility of claims of new discoveries based on “statistically significant” findings. There has been much progress toward documenting and addressing several causes of this lack of reproducibility (e.g., multiple testing, P-hacking, publication bias, and under-powered studies). However, we believe that a leading cause of non-reproducibility has not yet been adequately addressed: Statistical standards of evidence for claiming discoveries in many fields of science are simply too low. Associating “statistically significant” findings with P < 0.05 results in a high rate of false positives even in the absence of other experimental, procedural and reporting problems. For fields where the threshold for defining statistical significance is P<0.05, we propose a change to P<0.005. This simple step would immediately improve the reproducibility of scientific research in many fields. Results that would currently be called “significant” but do not meet the new threshold should instead be called “suggestive.” While statisticians have known the relative weakness of using P≈0.05 as a threshold for discovery and the proposal to lower it to 0.005 is not new (1, 2), a critical mass of researchers now endorse this change. We restrict our recommendation to claims of discovery of new effects. We do not address the appropriate threshold for confirmatory or contradictory replications of existing claims. We also do not advocate changes to discovery thresholds in fields that have already adopted more stringent standards (e.g., genomics and high-energy physics research; see Potential Objections below). We also restrict our recommendation to studies that conduct null hypothesis significance tests. We have diverse views about how best to improve reproducibility, and many of us believe that other ways of summarizing the data, such as Bayes factors or other posterior summaries based on clearly articulated model assumptions, are preferable to P-values. However, changing the P-value threshold is simple and might quickly achieve broad acceptance

Homologous recombination DNA repair defects in PALB2- associated breast cancers

Abstract: Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD

Arthroscopic Management of Posterior Instability due to “Floating” Posterior Inferior Glenohumeral Ligament Lesions

The “floating” posterior inferior glenohumeral ligament (floating PIGHL) is an uncommon cause of posterior shoulder instability. This pathologic lesion, defined as detachment of both the origin of the PIGHL (posterior Bankart lesion) and insertion of the of the PIGHL from its humeral head insertion site, often results in significant and persistent shoulder instability symptoms. An effective surgical technique for arthroscopic repair of a floating PIGHL lesion is described and demonstrated

Surgical Management of Shoulder Heterotopic Ossification

The formation of heterotopic ossification around the shoulder is a rare but potentially debilitating condition. It is found most commonly around the hip and is usually associated with an inciting event such as trauma, burn, previous surgery, or traumatic brain/spinal cord injury. The formation of shoulder heterotopic ossification following arthroscopic surgery is very uncommon, with few data pertaining to it in the current literature. Formation of heterotopic ossification in the shoulder after arthroscopic surgery typically occurs around the acromioclavicular joint and in the subacromial space. This location may lead to chronic pain and decreased mobility. The purpose of this article is to describe an arthroscopic technique for excision of heterotopic ossification

Techniques and Tips for Identification of Comma Tissue in Subscapularis Tears

Identifying and repairing subscapularis tears can be challenging for the arthroscopic surgeon and is commonly related to the difficulty in accurately recognizing the distorted anatomy that may be encountered. Defining and differentiating this anterior glenohumeral joint anatomy are often made even more challenging in clinical situations in which large, retracted subscapularis and anterosuperior tears are present. Identifying the “comma tissue” during the initial arthroscopic assessment is very helpful because it provides an important anatomic landmark that not only serves to orient the surgeon but also facilitates reduction and repair of these tears. Identification of the comma tissue is sometimes a critical surgical step in subscapularis repair, and we provide tips and techniques that can aid the surgeon in reliably and reproducibly recognizing and incorporating the comma tissue

Arthroscopic Subscapularis Repair Using a Subacromial View

As a result of the continued improvement in arthroscopic equipment and techniques, subscapularis tears are now more reliably identified and are being repaired at higher rates than previously reported. Whereas small upper-border subscapularis tears can usually be effectively managed using an intra-articular view, larger tears often cannot be fully visualized with a standard 30° arthroscope when viewed from the posterior portal. These tears may require either using a 70° arthroscope or viewing through the standard 30° arthroscope from a subacromial portal-site location to completely visualize the tear. This article illustrates and discusses the advantages of using a subacromial-space portal site to view and arthroscopically manage large subscapularis tears

Rotator Interval Plication: The “Seamster” Technique

The indications and best technique for plication of the rotator interval capsule, performed as a supplemental procedure at the time of arthroscopic shoulder stabilization, remain a controversial topic. There are currently no well-accepted surgical indication guidelines that have been established. Several biomechanical studies, however, have demonstrated the important contribution of the rotator interval capsule to stability of the glenohumeral joint, and the utilization of rotator interval plication in patients with glenohumeral instability has been supported in several publications. The indications for and surgical steps to accomplish the arthroscopic “seamster” technique for rotator interval plication, used by the authors for >20 years, is described

Medialized Rip-Stop Convergence Technique for Retracted Rotator Cuff Tears

Attempts to restore the anatomical footprint during rotator cuff repair for retracted, relatively immobile tears can be difficult. In some cases, it can lead to excessive tension of the repair. Previous studies have noted improved clinical outcomes when repair tension is not excessive, and medialization of the anatomical footprint has been suggested as a technique that can help surgeons repair large, retracted tears without excessive tension and achieve improved clinical outcomes. Of note, excessive tension when restoring the rotator cuff tendon to the anatomical footprint is not limited to large, retracted tears. In some cases, restoring small- and medium-sized tears to the anatomical footprint also can lead to excessive tension. Therefore, it is not uncommon for the authors to employ some degree of footprint medialization even for repair of small- or medium-sized tears if repair to the anatomical footprint will lead to excess tension. The purpose of this article and video demonstration is to provide instruction for a reproducible rotator cuff technique using a medialized single-row rip-stop construct combined with convergence